1

Non-invasive measurement of the iron overload in the human

body

SIF 05 Catania 09282005

Mauro Marinelli12 Barbara Gianesin12 Antonella Lavagetto3 Martina Lamagna3 Eraldo Oliveri 12 Giuliano Sobrero2 Laura Terenzani3 Gian Luca Forni3

1Physics Department University of Genova Genova Italy 2National Institute of Nuclear Physics (INFN) Genova 3Centro della Microcitemia e Anemie Congenite Ospedali Galliera Genova Italy

THALAS - Gr V INFN

2

Patients suffering from Cooleyrsquos anemia (Thalassemia major) need frequent blood transfusions Transfused red cell iron accumulates in

tissues and organs with toxic effects

The most common method for iron evaluation is the liver biopsy

Assessment of body-iron accumulation is essential for managing therapy of iron-chelating diseases characterized by iron overload

such as thalassemia hereditary hemochromatosis and other forms of severe anemia

Although chemical analysis of liver biopsy samples is considered the gold standard for determining the Liver Iron Concentration

hellipconcern has been raised that variability in the distribution of liver iron deposition exists and might lead to errors as high as 200 in

assessing body iron burden by biopsyAm J Clinical Phathology 2005 123 146-152

3

Biosusceptometry

BB

Magnet Pickup

B

The magnetic field flux threaded with the pickup is slightly modified by the diamagnetic (mainly from

water) and paramagnetic (iron) properties of tissues

4

The magnetization is proportional to the iron concentration and to the applied magnetic field

The magnetic moments of the iron atoms are randomly oriented when no magnetic field is applied

In the presence of the applied magnetic field the magnetic moments line up

B

B

B

The thermal motion keeps them from lining up entirely but there is some net alignment

B

B

B

5

Curie law

T

C) (p)

mKg

K10 812(

2

3

5-Fe

p iron effective magnetic moment (Bohr magneton)Ferric iron (Fe3+) ion p = 59Ferritin-Hemosiderin iron p 4

The apparatus calibration has been verified by checking the Curie law with solutions of hexahydrate ferric chloride

(FeCl36H2O)

Susceptibilities arise from competition between the aligning effect of the applied field and thermal vibrations

6

0 1000 2000 10000

~400normal value

400-1000light

overload

1000-2000moderateoverload

gt 2000 severe

overload

ccgFe

The iron contribution to the magnetic field is about 10 of the water contribution

Solution 620 gFecc (p=4) B109B 7

BB

6109 The magnetic field near the surface of the spherical sample of water is 9 ppm smaller than the field present without the sample

Water

Applied magnetic fieldB

7

SQUID Susceptometer

R Fisher E Eich R Engelhardt H C Heinrich M Kessler and P Nielsen ldquoThe calibration problem in liver iron susceptometry rdquo in Advances in biomagnetism SJ Williamson et al Ed New York 1990 pp 501ndash504

8

Susc ratti 1

The magnetic field flux threaded with the pickup coil is modified by the apparatus thermal expansion It is necessary for temperature control on the milliKelvin scale to reach the required sensitivity

Twelve living rats has been measured with a smaller prototype susceptometer

MagnetPickupPickup

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

2

Patients suffering from Cooleyrsquos anemia (Thalassemia major) need frequent blood transfusions Transfused red cell iron accumulates in

tissues and organs with toxic effects

The most common method for iron evaluation is the liver biopsy

Assessment of body-iron accumulation is essential for managing therapy of iron-chelating diseases characterized by iron overload

such as thalassemia hereditary hemochromatosis and other forms of severe anemia

Although chemical analysis of liver biopsy samples is considered the gold standard for determining the Liver Iron Concentration

hellipconcern has been raised that variability in the distribution of liver iron deposition exists and might lead to errors as high as 200 in

assessing body iron burden by biopsyAm J Clinical Phathology 2005 123 146-152

3

Biosusceptometry

BB

Magnet Pickup

B

The magnetic field flux threaded with the pickup is slightly modified by the diamagnetic (mainly from

water) and paramagnetic (iron) properties of tissues

4

The magnetization is proportional to the iron concentration and to the applied magnetic field

The magnetic moments of the iron atoms are randomly oriented when no magnetic field is applied

In the presence of the applied magnetic field the magnetic moments line up

B

B

B

The thermal motion keeps them from lining up entirely but there is some net alignment

B

B

B

5

Curie law

T

C) (p)

mKg

K10 812(

2

3

5-Fe

p iron effective magnetic moment (Bohr magneton)Ferric iron (Fe3+) ion p = 59Ferritin-Hemosiderin iron p 4

The apparatus calibration has been verified by checking the Curie law with solutions of hexahydrate ferric chloride

(FeCl36H2O)

Susceptibilities arise from competition between the aligning effect of the applied field and thermal vibrations

6

0 1000 2000 10000

~400normal value

400-1000light

overload

1000-2000moderateoverload

gt 2000 severe

overload

ccgFe

The iron contribution to the magnetic field is about 10 of the water contribution

Solution 620 gFecc (p=4) B109B 7

BB

6109 The magnetic field near the surface of the spherical sample of water is 9 ppm smaller than the field present without the sample

Water

Applied magnetic fieldB

7

SQUID Susceptometer

R Fisher E Eich R Engelhardt H C Heinrich M Kessler and P Nielsen ldquoThe calibration problem in liver iron susceptometry rdquo in Advances in biomagnetism SJ Williamson et al Ed New York 1990 pp 501ndash504

8

Susc ratti 1

The magnetic field flux threaded with the pickup coil is modified by the apparatus thermal expansion It is necessary for temperature control on the milliKelvin scale to reach the required sensitivity

Twelve living rats has been measured with a smaller prototype susceptometer

MagnetPickupPickup

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

3

Biosusceptometry

BB

Magnet Pickup

B

The magnetic field flux threaded with the pickup is slightly modified by the diamagnetic (mainly from

water) and paramagnetic (iron) properties of tissues

4

The magnetization is proportional to the iron concentration and to the applied magnetic field

The magnetic moments of the iron atoms are randomly oriented when no magnetic field is applied

In the presence of the applied magnetic field the magnetic moments line up

B

B

B

The thermal motion keeps them from lining up entirely but there is some net alignment

B

B

B

5

Curie law

T

C) (p)

mKg

K10 812(

2

3

5-Fe

p iron effective magnetic moment (Bohr magneton)Ferric iron (Fe3+) ion p = 59Ferritin-Hemosiderin iron p 4

The apparatus calibration has been verified by checking the Curie law with solutions of hexahydrate ferric chloride

(FeCl36H2O)

Susceptibilities arise from competition between the aligning effect of the applied field and thermal vibrations

6

0 1000 2000 10000

~400normal value

400-1000light

overload

1000-2000moderateoverload

gt 2000 severe

overload

ccgFe

The iron contribution to the magnetic field is about 10 of the water contribution

Solution 620 gFecc (p=4) B109B 7

BB

6109 The magnetic field near the surface of the spherical sample of water is 9 ppm smaller than the field present without the sample

Water

Applied magnetic fieldB

7

SQUID Susceptometer

R Fisher E Eich R Engelhardt H C Heinrich M Kessler and P Nielsen ldquoThe calibration problem in liver iron susceptometry rdquo in Advances in biomagnetism SJ Williamson et al Ed New York 1990 pp 501ndash504

8

Susc ratti 1

The magnetic field flux threaded with the pickup coil is modified by the apparatus thermal expansion It is necessary for temperature control on the milliKelvin scale to reach the required sensitivity

Twelve living rats has been measured with a smaller prototype susceptometer

MagnetPickupPickup

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

4

The magnetization is proportional to the iron concentration and to the applied magnetic field

The magnetic moments of the iron atoms are randomly oriented when no magnetic field is applied

In the presence of the applied magnetic field the magnetic moments line up

B

B

B

The thermal motion keeps them from lining up entirely but there is some net alignment

B

B

B

5

Curie law

T

C) (p)

mKg

K10 812(

2

3

5-Fe

p iron effective magnetic moment (Bohr magneton)Ferric iron (Fe3+) ion p = 59Ferritin-Hemosiderin iron p 4

The apparatus calibration has been verified by checking the Curie law with solutions of hexahydrate ferric chloride

(FeCl36H2O)

Susceptibilities arise from competition between the aligning effect of the applied field and thermal vibrations

6

0 1000 2000 10000

~400normal value

400-1000light

overload

1000-2000moderateoverload

gt 2000 severe

overload

ccgFe

The iron contribution to the magnetic field is about 10 of the water contribution

Solution 620 gFecc (p=4) B109B 7

BB

6109 The magnetic field near the surface of the spherical sample of water is 9 ppm smaller than the field present without the sample

Water

Applied magnetic fieldB

7

SQUID Susceptometer

R Fisher E Eich R Engelhardt H C Heinrich M Kessler and P Nielsen ldquoThe calibration problem in liver iron susceptometry rdquo in Advances in biomagnetism SJ Williamson et al Ed New York 1990 pp 501ndash504

8

Susc ratti 1

The magnetic field flux threaded with the pickup coil is modified by the apparatus thermal expansion It is necessary for temperature control on the milliKelvin scale to reach the required sensitivity

Twelve living rats has been measured with a smaller prototype susceptometer

MagnetPickupPickup

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

5

Curie law

T

C) (p)

mKg

K10 812(

2

3

5-Fe

p iron effective magnetic moment (Bohr magneton)Ferric iron (Fe3+) ion p = 59Ferritin-Hemosiderin iron p 4

The apparatus calibration has been verified by checking the Curie law with solutions of hexahydrate ferric chloride

(FeCl36H2O)

Susceptibilities arise from competition between the aligning effect of the applied field and thermal vibrations

6

0 1000 2000 10000

~400normal value

400-1000light

overload

1000-2000moderateoverload

gt 2000 severe

overload

ccgFe

The iron contribution to the magnetic field is about 10 of the water contribution

Solution 620 gFecc (p=4) B109B 7

BB

6109 The magnetic field near the surface of the spherical sample of water is 9 ppm smaller than the field present without the sample

Water

Applied magnetic fieldB

7

SQUID Susceptometer

R Fisher E Eich R Engelhardt H C Heinrich M Kessler and P Nielsen ldquoThe calibration problem in liver iron susceptometry rdquo in Advances in biomagnetism SJ Williamson et al Ed New York 1990 pp 501ndash504

8

Susc ratti 1

The magnetic field flux threaded with the pickup coil is modified by the apparatus thermal expansion It is necessary for temperature control on the milliKelvin scale to reach the required sensitivity

Twelve living rats has been measured with a smaller prototype susceptometer

MagnetPickupPickup

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

6

0 1000 2000 10000

~400normal value

400-1000light

overload

1000-2000moderateoverload

gt 2000 severe

overload

ccgFe

The iron contribution to the magnetic field is about 10 of the water contribution

Solution 620 gFecc (p=4) B109B 7

BB

6109 The magnetic field near the surface of the spherical sample of water is 9 ppm smaller than the field present without the sample

Water

Applied magnetic fieldB

7

SQUID Susceptometer

R Fisher E Eich R Engelhardt H C Heinrich M Kessler and P Nielsen ldquoThe calibration problem in liver iron susceptometry rdquo in Advances in biomagnetism SJ Williamson et al Ed New York 1990 pp 501ndash504

8

Susc ratti 1

The magnetic field flux threaded with the pickup coil is modified by the apparatus thermal expansion It is necessary for temperature control on the milliKelvin scale to reach the required sensitivity

Twelve living rats has been measured with a smaller prototype susceptometer

MagnetPickupPickup

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

7

SQUID Susceptometer

R Fisher E Eich R Engelhardt H C Heinrich M Kessler and P Nielsen ldquoThe calibration problem in liver iron susceptometry rdquo in Advances in biomagnetism SJ Williamson et al Ed New York 1990 pp 501ndash504

8

Susc ratti 1

The magnetic field flux threaded with the pickup coil is modified by the apparatus thermal expansion It is necessary for temperature control on the milliKelvin scale to reach the required sensitivity

Twelve living rats has been measured with a smaller prototype susceptometer

MagnetPickupPickup

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

8

Susc ratti 1

The magnetic field flux threaded with the pickup coil is modified by the apparatus thermal expansion It is necessary for temperature control on the milliKelvin scale to reach the required sensitivity

Twelve living rats has been measured with a smaller prototype susceptometer

MagnetPickupPickup

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

9

Susc ratti 2

Marinelli M1 Gianesin B1 Avignolo C2

Minganti V3 Parodi S4

1 Dpt of Physics and National Institute of Nuclear Physics (INFN)2 Dpt of Oncology Biology and Genetics3 Dpt of Chemistry and Pharmaceutical and Alimentary Technology4 Department of Oncology Biology and Genetics and National Inst for Res on Canc of Genoa (IST) University of Genoa Genoa Italy

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

10

(OP)(OP)

(IP)(IP)

(IP)(IP)

(OP)(OP)

(OM)(OM)

(IM)(IM) Fiberglas structure

Thermal shield

THALAS - Gr V INFN

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

11

V

)()( rdrrg 3

The magnetic field in this entire region is lower than 19 10-2 T

CEI EN 60601-2-3 1997-02

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

12

Inner magnets

Outer magnetsMagnet construction

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

13

Foto magneti e pick-up

Magnets Pickup

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

14

IM-IP OM-OP

IM

IP

IP

I=38Arms f=2345Hzgmax~ 1100Vm3

IM-IP

OM

OP

OP

I=19Arms f=195Hzgmax~ 800 Vm3

OM-OP

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

15

IM-OP OM-IP

OM

IP

IP

OM-IP

I=19Arms f=195Hzgmax~ 2600 Vm3

OP

OP

IM

IM-OP

I=38Arms f=2345Hzgmax~ 1500Vm3

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

16

x0

We average a few differences between the signals with the stretcher in and out of the sensitivity region to account for the changes of the environment magnetic properties

This body position is to scan the whole torso Simply shifting the body allows measuring the magnetic signal of other body parts for instance the head

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

17

Magnetization flux

Eddy current flux

Eddy Current SignalEddy Current Signal

Because of the inductance of the eddy currents loops within the sample and the solution resistivity the delay of the eddy currents relative to the induced electric field is negligible This is true also for the eddy currents induced in the human body

Magnetization signal

Eddy Current signal

y

x

B

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

18

Variando la concentrazione di NaCl in soluzione con 2l acqua deionizzata si osserva

bull il diamagnetismo del sale sul segnale in fasebull le correnti parassite sul segnale a 90

h=15cm

r=775cm

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

19

Small holes are evenly distributed on each of the phantom plastic slices We poured paramagnetic powder equivalent to 3 g of Fe3+

and 15 g of Fe3+ inside the holes placed in the phantom liver

region

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

Because of ~100 nV error the minimum quantity of detectable iron inside the entire liver region of the phantom is ~130 mg of Fe3+ or ~270 mg of iron with an effective magnetic moment of 4 B

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

20

A few anthropometric data of V010 Height 184 m Weigh 90 Kg BMI 27 Kgm^2 Area of the torso cross-section 819 cm2 Torso mean thickness 233 cm x coordinate of the liver center -12 cm

x0

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so p

rofi

le [

cm]

x

V010 torso profile

Stretcher plane

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

21

A few anthropometric data of V037 Height 157 m Weigh 48 Kg BMI 19 Kgm2

Area of the torso cross-section 452 cm2 Torso mean thickness 162 cm x coordinate of the liver center -10 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

V037 torso profile

Tor

so p

rofi

le [

cm]

xStretcher plane

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

22

Patient P002 and volunteer V005 have similar anthropometric characteristics

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

23

Patient P002 after four months under iron depletive therapy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Magnetization signalFeb 22 2005

Mag

neti

c Si

gnal

[V

]

x

Magnetization signalJun 16 2005

Eddy Current signalFeb 22 2005 Eddy Current signal

Jun 16 2005

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

24

Patient P029 before and after the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

25

Patient P003 before and after 12 phlebotomies

Eddy Current signalbefore 12 phlebotomies

March 7 2005-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current signalafter 12 phlebotomies

May 27 2005

Mag

neti

c Si

gnal

[V

]Magnetization signal

after 12 phlebotomiesMay 27 2005

Magnetization signalbefore 12 phlebotomies

March 7 2005

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

26

-5

0

5

10

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the phantom center [cm]

Mag

neti

zati

on S

igna

l [V

]

no added powder

3 g of Fe3+

15 g of Fe3+

x

signal of iron overload difference between the actual magnetization signal and the signal estimate of the patient supposed depleted by the iron overload

Phantom signals

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

27

The eddy current signal does not depend on the iron

In all the patient measurements we never noticed the iron overload skewness on the eddy current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

PATIENT 002 Magnetization signal

VOLUNTEER 005Magnetization signal

Mag

neti

c S

ign

al [V

]

x

PATIENT 002 Eddy Current signal

VOLUNTEER 005Eddy Current signal

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20Magnetic field axis relative to the torso center [cm]

Mag

neti

c si

gnal

[V

]

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 06 2005 x

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

The concentration of iron in the tissues as free aqua ions is not significant [J F Schenck E A Zimmerman ldquoReview Article High-field magnetic resonance imaging of brain iron birth of a biomarkerrdquoNMR Biomed no 17 pp 433-445 2004]

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

28

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c S

ign

al [V

]

x

Healthy Volunteer V037

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal

Magnetization Signal

Mag

neti

c Si

gnal

[V

]

x

Healthy Volunteer V010

The eddy current and magnetization signals of a person without iron overload have a similar dependence on the body size

The estimation of the signal of the patient supposed depleted by the iron overload is strongly based on his eddy curent signal

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

29

The expected magnetization signal from the statistical model using the eddy current signal and the other patients data

measured before the spleenectomy

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

x

Statistical Model Estimate

Magnetization signalafter spleenectomy

Sept 06 2005

Eddy Current signalafter spleenectomy

Sept 062005

Magnetization signal before spleenectomy

June 20 2005

Eddy Current signalbefore spleenectomy

June 20 2005

Mag

neti

c si

gnal

[V

]

Magnetic field axis relative to the torso center [cm]

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

30

P002 data Feb2205 June1605 Height 152 m 152 m Weigh 55 Kg 562 Kg BMI 238 Kgm2 243 Kgm2 Area of the torso cross-section 512 cm2 524 cm2

Torso mean thickness 183 cm 187 cm coordinate of the liver center (x) -5 cm -4 cm

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Mag

neti

c Si

gnal

[V

]

Statistical Model EstimateJune 16 2005

Magnetization signalJune 16 2005

Eddy Current SignalFeb 22 2005

x

Magnetization signalFeb 22 2005

Eddy Current SignalJune 16 2005

Statistical Model EstimateFeb 22 2005

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm]

Feb 22 2005

June 6 2005

x

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

31

P003 data March 7 05 May 27 05 Height 182 m 182 m Weight 905 Kg 885 Kg BMI 237 Kgm2 267 Kgm2

Area of the torso cross-section 855 cm2 821 cm2

Torso mean thickness 241 cm 237 cm Coordinate of the liver center (x) -12 cm -12 cm

Iron overload bull March 7 2005 ~10 gbull May 27 2005 ~75 g

The iron removed by the 12 phlebotomies is 27g

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Eddy Current Signal before

12 phlebotomiesMag

net

ic S

ign

al [V

]

Statistical Model Estimate before 12 phlebotomies

x

Magnetization signalbefore 12 phlebotomies

March 7 2005

Magnetization signalafter 12 phlebotomies

May 27 2005

Eddy Current Signal after

12 phlebotomies

Statistical Model Estimate after

12 phlebotomies

0

5

10

15

20

25

30

-20 -15 -10 -5 0 5 10 15 20

Tor

so P

rofi

le [

cm] March 7 2005

May 27 2005

x

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

32

Measured and calculated magnetization signal of a few volunteers

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V075

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V069

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on S

igna

l [V

]

x

V072

-8

-6

-4

-2

0

2

4

-20 -15 -10 -5 0 5 10 15 20

Magnetic field axis relative to the torso center [cm]

Statistical Model Estimate

Measured Signal

Mag

neti

zati

on s

ign

al [V

]

x

V070

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

33

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -8 cm V

Training setTest set

Cou

nt

error [V]

0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = -4 cm

V

Training setTest set

Cou

nt

error [V] 0

2

4

6

8

10

12

14

16

-2 -15 -1 -05 0 05 1 15 2

STATISTICAL MODELX = 0

V

Training setTest set

Cou

nt

error [V]

0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -8 cmV

Training+Test set

Cou

nt

error [V] 0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORK X = -4 cmV

Training+Test set

Cou

nt

error [V]0

5

10

15

20

25

30

-2 -15 -1 -05 0 05 1 15 2

NEURAL NETWORKX = 0

V

Training+Test set

Cou

ntRange [V]

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

34

The measured reduction of the iron overload is compared with its estimate according with the therapy

0

2

4

6

8

0 2 4 6 8

P002P003 P006P008

y = 030+ 044x R= 081

Mea

sure

d r

edu

ctio

n [

g]

Therapy estimate [g]

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

35

Correlation with serum-ferritinCorrelation of the iron overloads of all 40 patients

measured with their blood serum-ferritin

0

5

10

15

0 4 103 8 103 12 104

y = 038 + 00012x R= 068

Iron

ove

rloa

d [

g]

Serum-ferritin [gl]

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

36

Correlation with SQUIDThe Liver Iron Concentration (LIC) via SQUID

susceptometry on a subset of 30 patients is compared with the LIC obtained by the susceptometer data

0

5

10

15

0 5 10 15

y = -050 + 19x R= 077

Su

scep

tom

eter

LIC

[m

gg w

et]

SQUID LIC [mggwet

]

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

37

Referto

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration

38

A BC

D

A 1 liter B 2 literC 3 liter D 4 liter

-02

0

02

04

06

08

1

-30 -20 -10 0 10 20 30

Mag

neti

zati

on s

igna

l of

di 1

gr d

i Fe3+

ev

enly

dis

trib

ute

d in

the

reg

ion

s A

B C

D

Magnetic field axis relative to the torso center [cm]

A

B

C

D

• Non-invasive measurement of the iron overload in the human body
• Problema medico
• Biosusceptometry
• Magnetic moments
• Curie law
• Iron contribution
• SQUID Susceptometer
• Susc ratti 1
• Susc ratti 2
• Magnets and shield
• Biosusceptometer
• Magnets
• Foto magneti e pick-up
• IM-IP OM-OP
• IM-OP OM-IP
• Stretcher
• Eddy Current Signal
• PowerPoint Presentation
• Phantom
• V010
• V037
• P002 ndash V005
• P002 helliptherapy
• P029 hellipspleenectomy
• P003 12 phlebotomies
• Iron overload
• The eddy current signal does not depend on the iron
• Eddy current and magnetization signals
• P029
• P002 Statistical Estimate
• P003 Statistical Estimate
• Measured and calculated magnetization signal of a few volunteers
• Errors
• Correlation with therapy
• Correlation with serum-ferritin
• Correlation with SQUID
• Referto
• Calibration