g-exj-1030713 may 2012 cardiac mri diagnostic backgrounder note: these slides are for use in...
TRANSCRIPT
G-EXJ-1030713May 2012
CARDIAC MRI
Diagnostic Backgrounder
NOTE: These slides are for use in educational oral presentations only. If any published figures/tables from these slides are to be used for another purpose (e.g. in printed materials), it is the individual’s responsibility to apply for the relevant permission. Specific local use requires local approval
2G-EXJ-1030713May 2012
Outline
● Introduction to iron overload
● Assessing cardiac iron loading– echocardiography– cardiac MRI
● Cardiac MRI in practice– preparation of the patient– acquisition of the image– analysis of the data
• Excel spreadsheet• ThalassaemiaTools (CMRtools)• cmr42
• FerriScan• MRmap• MATLAB
● Summary
MRI = magnetic resonance imaging.
G-EXJ-1030713May 2012
Introduction to iron overload
4G-EXJ-1030713May 2012
Introduction to iron overload
● Iron overload is common in patients who require intermittent or regular blood transfusions to treat anaemia and associated conditions
– it may be exacerbated in some conditions by excess gastrointestinal absorption of iron
● Iron overload can lead to considerable morbidity and mortality1
● Excess iron is deposited in major organs, resulting in organ damage
– the organs that are at risk of damage due to iron overload include the liver, heart, pancreas, thyroid, pituitary gland, and other endocrine organs2,3
1Ladis V, et al. Ann NY Acad Sci. 2005;1054:445-50. 2Gabutti V, Piga A. Acta Haematol. 1996;95:26-36. 3Olivieri NF. N Engl J Med. 1999;341:99-109.
5G-EXJ-1030713May 2012
Importance of analysing cardiac iron
● In β-thalassaemia major, cardiac failure and arrhythmia are risk factors for mortality1
– signs of myocardial damage due to iron overload: arrhythmia, cardiomegaly, heart failure, and pericarditis2
– heart failure has been a major cause of death in β-thalassaemia patients in the past (50–70%)1,3
● In MDS, the results of studies are less comprehensible
– the reported proportion of MDS patients with cardiac iron overload is inconsistent; from high to only a small proportion of MDS patients4–7
– cardiac iron overload occurs later than does liver iron overload4,7,8
– however, cardiac iron overload can have serious clinical consequences in MDS patients
1Borgna-Pignatti C, et al. Haematologica. 2004;89:1187-93. 2Gabutti V, Piga A. Acta Haematol. 1996;95:26-36. 3. Modell B, et al. Lancet. 2000;355:2051-2. 4Jensen PD, et al. Blood. 2003;101:4632-9. 5Chacko J, et al. Br J Haematol. 2007;138:587-93. 6Konen E, et al. Am J Hematol. 2007;82:1013-6. 7Di Tucci AA, et al. Haematologica. 2008;93:1385-8. 8Buja LM, Roberts WC. Am J Med. 1971;51:209-21.
6G-EXJ-1030713May 2012
BaselineLatest follow-up
p < 0.001
p < 0.001
cT2* ≤ 20 ms cT2* < 10 ms
Pat
ien
ts (
%)
cT2* = cardiac T2*.
1Thomas AS, et al. Blood. 2010;116:[abstract 1011]. 2Modell B, et al. Lancet. 2000;355:2051-2.
Importance of analysing cardiac iron (cont.)
● In 2010, the overall mortality rate of β-thalassaemia major patients in the UK was substantially lower than a decade ago (1.65 vs 4.3 per 1,000 patient years)1,2
– due to improved monitoring and management of iron overload over the last decade, 77% of patients have normal cardiac T2*1
– cardiac iron overload is no longer the leading cause of death in this population1
60
1723
7
0
10
20
30
40
50
60
70
7G-EXJ-1030713May 2012
Cardiac T2*: Overview of correlations with other measurements
1Wood JC, et al. Blood. 2004;103:1934-6. 2Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 3Tanner MA, et al. J Cardiovasc Magn Reson. 2006;8:543-7. 4Kirk P, et al. Circulation. 2009;120:1961-8.5Westwood MA, et al. J Magn Reson Imaging. 2005;22:229-33.
†For thalassaemia, but not sickle cell.APFR = atrial peak filling rate; EPFR = early peak filling rate; LIC = liver iron concentration; SF = serum ferritin.
Weak or no correlation
Transfusion duration† ↑1
Ventricular dysfunction ↑1-3
Arrhythmia and heart failure ↑4
APFR↓ EPFR:APFR↑5
Need for cardiac medication↑1-2
T2*↓
SF and LIC1-3
8G-EXJ-1030713May 2012
LVE
F (
%)
0
50
70
40
30
20
10
60
80
90
0 20 40 60 9080 10010 30 50 70Cardiac T2* (ms)
Cardiac T2* value of 37 ms in a normal heart
Cardiac T2* value of 4 ms in a significantly iron-overloaded heart
LVEF = left-ventricular ejection fraction. Anderson LJ, et al. Eur Heart J. 2001;22:2171-9.
Normal T2* range
Normal LVEF range
Cardiac T2*: Relationship with LVEF
Myocardial T2* values < 20 ms are associated with a progressive and significant decline in LVEF
9G-EXJ-1030713May 2012
0.1
Cardiac T2*: Relationship with cardiac failure and arrhythmia
Kirk P, et al. Circulation. 2009;120:1961-8.
T2* < 10 ms: relative risk 159 (p < 0.001)T2* < 6 ms: relative risk 268 (p < 0.001)
Cardiac failure
Pro
po
rtio
n o
f p
atie
nts
d
evel
op
ing
car
dia
c fa
ilu
re
Follow-up time (days)
600 120 180 240 300 360
0.3
0.2
0
0.4
0.5
0.6< 6 ms
6–8 ms
8–10 ms
> 10 ms
Arrhythmia
600 120 180 240 300 360
0.15
0.10
0.05
0
0.20
0.25
0.30
< 10 ms
10–20 ms
> 20 ms
T2* < 20 ms: relative risk 4.6 (p < 0.001)T2* < 6 ms: relative risk 8.65 (p < 0.001)
Follow-up time (days)P
rop
ort
ion
of
pat
ien
ts w
ith
arr
hyt
hm
ia
Low myocardial T2* predicts a high risk of developing cardiac failure and arrhythmia
G-EXJ-1030713May 2012
Assessing cardiac iron overload
11G-EXJ-1030713May 2012
Assessing cardiac iron loading: Agenda
● Echocardiography
● Cardiac MRI
– advantages and disadvantages of cardiac MRI
– MRI: a non-invasive diagnostic tool
– T2* is the standard method for analysing cardiac iron
G-EXJ-1030713May 2012
Echocardiography
13G-EXJ-1030713May 2012
Assessing cardiac iron loading: Echocardiography
EF = ejection fraction.1Leonardi B, et al. JACC Cardiovasc Imaging. 2008;1:572-8. 2Hoffbrand AV. Eur Heart J. 2001;22:2140-1.
Pros Cons
• Readily available1
• Relatively inexpensive1
• Does not detect early damage2
• Echocardiographic diastolic function parameters correlate poorly with LVEF and T2*1
• Cannot directly or indirectly quantify cardiac iron levels
G-EXJ-1030713May 2012
Cardiac MRI
15G-EXJ-1030713May 2012
MRI: A non-invasive diagnostic tool
● Indirectly measures levels of iron in the heart
● MRI measures longitudinal (T1) and transverse (T2) relaxation times of the protons
– iron deposition disrupts the homogeneous magnetic field and shortens T1 and T2 times in a concentration-dependent manner
RF = radio-frequency.1Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96. 2Wood JC, et al. Circulation. 2005;112:535-43. 3Wang ZJ, et al. Radiology. 2005;234:749-55. 4Ghugre NR, et al. Magn Reson Med. 2006;56:681-6.
Protons
Magnetic field
RF/spin echo/gradient echo
Echo signal → T1, T2
Signal processing
Iron
16G-EXJ-1030713May 2012
MRI: A non-invasive diagnostic tool (cont.)
● If a spin-echo sequence is used, the relaxation time is T2
● If a gradient-echo sequence is used, it is T2*
● Cardiac MRI methods
– gradient-echo T2* MRI: most used in clinical practice
– spin-echo T2 MRI: less useful (motion artefacts common due to characteristics of the heart)
TE = echo time.Adapted from Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96.
Protons
Magnetic field
Most used in clinical practice:
Gradient echo
Image acquired at different TEs
Excel or software
T2* [ms}
R2* [Hz]=1,000/T2*
Spin echo
Image acquired at different TEs
Excel or software
T2* [ms}
R2* [Hz]=1,000/T2*
17G-EXJ-1030713May 2012
Assessing cardiac iron loading: Cardiac MRI
Advantages of MRI Disadvantages of MRI
• Non- invasive• Rapidly assesses iron content in the
septum of the heart• Relative iron burden can be
reproducibly estimated • Functional parameters can be
examined concurrently (e.g. LVEF)• Iron status of liver and heart can be
assessed in parallel• Allows longitudinal follow-up• Good correlation with morbidity
and mortality outcomes
• Indirect measurement of cardiac iron
• Requires MRI imager with dedicated imaging method
• Relatively expensive and varied availability
18G-EXJ-1030713May 2012
What are sequences?
Sequences are a set of radio-frequency and gradient pulses (slight tilts in the magnetization curves of the scanner) generated repeatedly during the scan, which produce echoes with varied amplitudes and shapes that will define the MR image
What is gradient echo?
A gradient-echo sequence is obtained after 2 gradient impulses are applied to the body, resulting in a signal echo that is read by the coils. In these sequences, the spins are not refocused and, therefore, are subject to local inhomogeneities, with a more rapid decay curve. For gradient-echo pulse sequences, the T2* relaxation times (which reflect these inhomogeneities) on the signal are more significant
1Image from Ridgway JP. J Cardiovasc Magn Reson. 2010;12:71.
FAQ: Cardiac MRI
19G-EXJ-1030713May 2012
Gradient relaxometry (T2*, R2*) is the method for analysing cardiac iron levels
1Guo H, et al. J Magn Reson Imaging. 2009;30:394-400. 2Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 3Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202:173-9.4Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96. 5Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9.6Hoffbrand AV. Eur Heart J. 2001;22:2140-1. 7He T, et al. Magn Reson Med. 2008;60:1082-9.
T2* (gradient echo) T2 (spin echo)
Pros • Greater sensitivity to iron deposition2
• Shorter acquisition time1
• Less affected by motion artefacts3
• More readily available3
• Easier to perform4
• Good reproducibility5
• Less affected by susceptibility artefacts1, due to metal implants, air–tissue interfaces, proximity to cardiac veins
Cons • More sensitive to static magnetic field inhomogeneity1
• Noise, motion, and blood artefacts can complicate analysis (particularly in heavily iron-loaded hearts)7
• Lack of sensitivity6
• Motion artefacts6
• Poor signal-to-background noise ratios at longer TEs6
• Longer acquisition time1
20G-EXJ-1030713May 2012
HIC = hepatic iron concentrationCarpenter JP, et al. J Cardiovasc Magn Reson. 2009;11 Suppl 1:P224.Hankins et al Blood. 2009;113:4853-4855.
30
25
20
15
10
5
0
0 200 400 600 800 1000
Liver R2* (Hz)H
IC (
mg
Fe/
g o
f d
ry w
eig
ht
live
r)
Hankins, et al.
Wood, et al.
Anderson, et al.
[Fe]
(m
g/g
dry
wt)
Cardiac R2* (Hz)
0
2
4
6
8
10
12
14
0 100 200 300 400
R2 = 0.82540
Liver MRICardiac MRI
Gradient relaxometry (T2*, R2*) can conveniently measure cardiac and liver iron
Cardiac and liver iron can be assessed together conveniently by gradient echo during the a single MRI measurement.
21G-EXJ-1030713May 2012
Cardiac T2* MRI is usually measured in the septum of the heart
Heart with normal iron levels
Heart with severe iron overload
Images courtesy of Dr J. de Lara Fernandes.
T2* = 22.8 ms or R2* = 43.9 Hz
T2* = 5.2 ms or R2* = 192 Hz
22G-EXJ-1030713May 2012
Conversion from T2* to R2* is a simple mathematical calculation: R2* = 1,000/T2*
Level of cardiac iron overload T2*, ms R2*, Hz
Normal 201 < 50
Mild, moderate 10–201 50–100
Severe < 102 > 100
1Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 2Kirk P, et al. Circulation. 2009;120:1961-8.
These values are only applicable to 1.5 T scanners1
What is R2*?
23G-EXJ-1030713May 2012
Why should the data be presented as R2* and not T2*?
● Seven whole hearts from patients with transfusion-dependent anaemias were assessed by histology and cardiac MRI
[Fe]
(m
g/g
dry
wt)
Cardiac T2* (ms)
[Fe]
(m
g/g
dry
wt)
0
2
4
6
8
10
12
14
0 10 20 30 40 50 60 70
R2 = 0.949
Cardiac R2* (Hz)
0
2
4
6
8
10
12
14
0 100 200 300 400
R2 = 0.82540
Carpenter JP, et al. J Cardiovasc Magn Reson. 2009;11 Suppl 1:P224.
R2* has a linear relationship with tissue iron concentration, which simplifies the interpretation of data
and allows comparison of changes over time
24G-EXJ-1030713May 2012 Anderson LJ, et al. Eur Heart J. 2001;22:2171-9.
Hockey stick effect? Or a more gradual relationship?
The relationship between cardiac T2*/R2* and LVEF
Heart T2* (ms)
LVE
F (
%)
R2* (s–1)LV
EF
(%
)
90
80
70
60
50
40
30
20
10
0
10 20 30 40 50 60 70 80 90 1000
100
80
60
40
20
0
0 50 100 150 200 250
Why should the data be presented as R2* and not T2*? (cont.)
R2* allows demonstration of cardiac risk in a more gradual way
25G-EXJ-1030713May 2012
Transform to R2*
Standard errors on a single measurement are approximately constant with R2*, but are non-uniform with T2*
Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9.
60
50
40
30
20
10
00 10 20 30 40 50 60
T2* second measurement (ms)
T2*
fir
st m
easu
rem
ent
(ms)
120
100
80
60
40
20
00 20 40 60 80 100 120
R2* second measurement (s–1)
R2*
fir
st m
easu
rem
ent
(s–
1)
Why should the data be presented as R2* and not T2*? (cont.)
R2* has a constant standard error that makes assessment of the significance of changes easier
G-EXJ-1030713May 2012
Cardiac T2* MRI in practice
27G-EXJ-1030713May 2012
MRI scanners
● Manufacturers– Siemens Healthcare (Erlangen, Germany; www.siemensmedical.com)– GE Healthcare (Milwaukee, WI, USA; www.gemedicalsystems.com)– Philips Healthcare (Best, the Netherlands; www.medical.philips.com)
● Magnetic field– T2* varies with magnetic field strength1
– need 1.5 T for cutoff levels of 20 ms (iron overload) and 10 ms (severe iron overload)1,2
● Cardiac package– needs to be acquired separately from the manufacturers. The cost is
about USD 40,000. However, in most centres, this is available since MRI is frequently used in non-iron-related cardiovascular imaging
– includes all necessary for acquisition of the image – sequences are included in Siemens and Philips Healthcare cardiac
packages, but for GE Healthcare they need to be acquired separately (note: variations may exist between countries)
1Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 2Kirk P, et al. Circulation. 2009;120:1961-8.
28G-EXJ-1030713May 2012
Cardiac T2* MRI in practice: The process
LIVER
TE ROI1.3 134
2.46 1143.62 994.78 815.94 70
7.1 598.26 499.42 40
10.58 3511.74 28
E 0.14925T2* 2.1 msR2* 476.1905 HzLIC 12.88801 mg/gLIC calculation according to: Hankins JS, et al. Blood. 2009;113:4853-5.
Normal >11.4 Light 3.8 - 11.4 Moderate 1.8-3.8 Severe <1.8 T2*Normal <88 Light 88-263 Moderate 263-555 Severe >555 R2*Normal <2 Light 2-7 Moderate 7-15 Severe >15 mg/g
y = 166.48552e-0.14925x
R² = 0.99845
0
20
40
60
80
100
120
140
160
0 2 4 6 8 10 12 14
Please insert the values of TE and ROI from an individual patient.
Please insert the value from the graph, encircled green.
T2*, R2*
*Time to manually calculate T2*/R2* values in an Excel spreadsheet depends on the experience of the physician.
1. Patientpreparation
(5 min)
2. Acquisition of the MRI image
(approx. 5-20 min)
3. Analysis ofMRI data
(time depends on experience*)
29G-EXJ-1030713May 2012
Cardiac T2* MRI in practice: The process (cont.)
● Preparation of the patient
● Acquisition of the image
● Analysis of the data (post-processing)
• Excel spreadsheet
• ThalassaemiaTools, CMRtools
• cmr42
• FerriScan
• MRmap
• MATLAB
G-EXJ-1030713May 2012
Preparation of the patient
31G-EXJ-1030713May 2012
Preparation of the patient
● Standard precautions need to be taken
● There is no need for peripheral vein access since no contrast agent is required
● Special care
– remove all infusion/medication pumps (e.g. with insulin, pain-relieving drugs)
– stop continuous i.v. application of ICT during the measurement
– ECG signal should be positioned according to scanner specifications
ECG = electrocardiography.
32G-EXJ-1030713May 2012
Cardiac T2* MRI in practice: The process (cont.)
● Preparation of the patient
● Acquisition of the image
● Analysis of the data (post-processing)
• Excel spreadsheet
• ThalassaemiaTools, CMRtools
• cmr42
• FerriScan
• MRmap
• MATLAB
G-EXJ-1030713May 2012
Acquisition of the image
34G-EXJ-1030713May 2012
Acquisition of the image: MRI pulse sequences
● Pulse sequences
– are a preselected set of defined radio-frequency and gradient pulses
– are computer programs that control all hardware aspects of the scan
– determine the order, spacing, and type of radio-frequency pulses that produce magnetic resonance images according to changes in the gradients of the magnetic field
● Several different pulse sequences exist1
– a gradient-echo sequence generates T2*
1Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96.
35G-EXJ-1030713May 2012
1Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 2Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9. 3He T, et al. J Magn Reson Imaging. 2007;25:1205-9. 4He T, et al. Magn Reson Med. 2008;60:1082-9. 5Pepe A, et al. J Magn Reson Imaging. 2006;23:662-8.
Sequence GroupNumber of echoes per breath-hold
Heart regions
Pre-puls
e
RR intervals
TR
Bright blood(Anderson et al.)1
London(Pennell)
1 (but multiple breath-holds)
1 (septum) No 1 Variable
Novel bright blood(Westwood et al)2
London(Pennell)
Multiple 1 (septum) No 1 Fixed
Black blood(He et al)3-4
London(Pennell)
Multiple 1 (septum) Yes 2 Fixed
Multi-slice(Pepe et al)5
Pisa(Pepe)
MultipleMulti-region
No 1 Fixed
The most common commercially available T2* acquisition techniques
The various techniques give clinically comparable results.2-3, 5
36G-EXJ-1030713May 2012
Acquisition of the image: TEs
● Images are taken at a minimum of 5 different TEs, normally 8‒121
● The choice of minimum TE determines the smallest measurable T21
• ideally, min TE 2 ms, max TE 17‒20 ms
● Different T2* acquisition techniques according to TE
• multiple breath-hold: acquire an image for each TE in separate breath-holds2
• single breath-hold multi-echo acquisition: acquire images for all TE during 1 breath-hold3
Mean R2* compared with true value in the case of synthetic images for different minimum TEs,
but same echo duration (18 ms)4
1Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202:173-9. 2Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 3Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9. 4Ghugre NR, et al. J Magn Reson Imaging. 2006;23:9-16.
500
450
400
350
300
250
200
150
100
50
00 100 200 300 400 500
True R2* (Hz)M
ea
n R
2*:
ra
mp
, d
ua
lto
ne
, &
u
nif
orm
(H
z)
Shortest TE = 2 msShortest TE = 1 msShortest TE = 4 msShortest TE = 5.5 msTrue
37G-EXJ-1030713May 2012
How does the MRI data output looks like?
Data visualizationMRI data output
1Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96.
During a single breath hold the pulse sequence run several times at increasing echo time (TE), generating data points
corresponding to decreased signal intensity1
Frame TE (ms) Mean ST
0 1.9 89.5
1 3.6 83.6
2 5.3 76.8
3 7.0 70.6
4 8.7 64.5
5 10.4 59.2
6 12.2 54.9
7 13.9 50.2
8 15.6 45.8
9 17.3 42.4
38G-EXJ-1030713May 2012
Which is recommended: single or multiple breath-hold technique?
Comparison of the 2 methods, single and multiple breath-hold, showed no significant skewing between T2* values in all patients with -thalassaemia major, regardless of their T2* value (see Bland-Altman plots)1
However, in cardiac MRI the most recommended technique is single breath-hold, because it allows quick acquisition of the information. This is especially important to avoid movement artefacts (heart beating, breathing) and assure the good quality of the MRI image
1Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9.
Patients with T2* < 20 ms1 Patients with T2* 20 ms 1
FAQ: Acquisition technique
39G-EXJ-1030713May 2012
Acquisition of the image
● Single breath-hold multi-echo acquisition
– take a short-axis slice of the ventricle (halfway between the base and the apex): orange line
– image acquisition should occur immediately after the R wave
– do not alter any settings that could alter TE (e.g. FOV)
Image courtesy of Dr J. de Lara Fernandes.
40G-EXJ-1030713May 2012
Cardiac T2* MRI in practice: The process (cont.)
● Preparation of the patient
● Acquisition of the image
● Analysis of the data (post-processing)
• Excel spreadsheet
• ThalassaemiaTools, CMRtools
• cmr42
• FerriScan
• MRmap
• MATLAB
G-EXJ-1030713May 2012
Analysis of the data (post-processing)
42G-EXJ-1030713May 2012
How T2* is calculated from the MRI output?
Data visualization
1Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96.
Curve Fitting
T2*
Noise level
T2* calculation is fitting a curve on the data points and calculating at what echo time no signal is left from iron (only noise)1
43G-EXJ-1030713May 2012
Analysis of the data
● The data can be analysed manually or using post-processing software
Manually Post-processing software
•Excel spreadsheet •ThalassaemiaTools (CMRtools)•cmr42
•FerriScan•MRmap•MATLAB
44G-EXJ-1030713May 2012
Analysis of the data (cont.)
Method Pros Cons
Excel spreadsheet • Low cost • Time-consuming• Tedious
ThalassaemiaTools (CMRtools)1
• Fast (1 min)2
• Easy to use• FDA approved
• GBP 3,000 per year
cmr42(3) • Easy to use• FDA approved3
• Can generate T2*/R2* and T2/R2 maps with same software
• Allows different forms of analysis• Generates pixel-wise fitting with
colour maps
• 40,000 USD first year costs• 12,000 USD per year after
FDA = Food and Drug Administration.1www.cmrtools.com/cmrweb/ThalassaemiaToolsIntroduction.htm. Accessed Dec 2010. 2Pennell DJ. JACC Cardiovasc Imaging. 2008;1:579-81.3www.circlecvi.com. Accessed Dec 2010.
45G-EXJ-1030713May 2012
Method Pros Cons
FerriScan1 • Centralized analysis of locally acquired data (206 active sites across 25 countries)
• Easy set-up on most MRI machines• EU approved• Validated on GE, Philips, and Siemens scanners
• USD 100 per scan • Patients data are sent to
reference centre
MRmap2 • Uses IDL runtime, which is a commercial software (less expensive than cmr42/CMRtools)
• Can quantify T1 and T2 map with the same software
• Purely a research tool• Not intended for diagnostic or
clinical use
MATLAB3 • Low cost • Available only locally • Physicists or engineers need to
write a MATLAB program for display and T2* measurement
1www.resonancehealth.com/resonance/ferriscan. Accessed Dec 2010. 2www.cmr-berlin.org/forschung/ mrmapengl/index.html. Accessed Dec 2010. 3Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202:173-9.
Analysis of the data (cont.)
46G-EXJ-1030713May 2012
What are the most common mistakes in analysing the data that could lead to a wrong interpretation of the T2* value?
Interpreting the data from cardiac MRI is usually quite straightforward; problems may arise when analysing data from patients with severe cardiac iron overload. In this case, the signal from heavily iron-loaded muscle will decay quickly and a single exponential decay curve does not fit the data well.1
Models exist that can help to solve this issue (see next slide):1. the offset model (Prof Wood and colleagues) 2. truncation of the data (Prof Pennell and colleagues)
Both models should give comparable results; the differences should not be clinically relevant
1Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202:173-9. 2Ghugre NR, et al. J Magn Reson Imaging. 2006;23:9-16.
Signal decay curve from a patient with T2* ≈ 5 ms, showing that the data do not fit well2
FAQ: Mistakes in analysing the data
47G-EXJ-1030713May 2012
What is truncation?
After the selection of the ROI, the signal decay can be fitted using different models. In the truncation model, the late points in the curve that form a plateau are subjectively discarded; the objective is to have a curve with an R2 > 0.995. A new single exponential curve is made by fitting the remaining signals.1 Generally, a truncation model should be used with the bright-blood technique to obtain more reproducible and more accurate T2* measurements1
What is an offset model?
The offset model consists of a single exponential with a constant offset. Using only the exponential model can underestimate the real T2* values (at quick signal loss at short TE, there is a plateau), while inclusion of the offset model into the fitting equation can improve this.2
Generally, the offset model is recommended to be used with the black-blood technique
1He T, et al. Magn Reson Med. 2008;60:1082-9. 2Ghugre NR, et al. J Magn Reson Imaging. 2006;23:9-16.
FAQ: Mistakes in analysing the data (cont.)
48G-EXJ-1030713May 2012
How to start measuring cardiac iron loading in a hospital? What steps need to be taken?
To start assessing cardiac iron loading by MRI, these steps can be followed:1. Check MRI machine requirements
• 1.5 T• calibrated
2. Buy cardiac package from the manufacturer. It must include all that is necessary for acquisition of the data (the sequences are included with Siemens and Philips Healthcare cardiac packages, but for GE Healthcare they need to be acquired separately)
3. Optional: buy software for analysing the data (if not, Excel spreadsheet can be used)
4. Highly recommended: training of personnel for acquisition of cardiac MR images (e.g. functional analyses)
5. Highly recommended: training of personnel on how to analyse the data with the chosen software
FAQ: How to start measuring cardiac iron loading?
49G-EXJ-1030713May 2012
Implementation of liver and cardiac MRI
1.5T MRI Scanner
Experienced radiologistExperienced radiologist
Cardiac acquisition package
Routine cardiac MR examsRoutine cardiac MR exams
Post-processing analysis
US$1.000.000
US$50.000US$40.000 or US$4.000/yor in-house or outsource
Yes
No
½ day training
1 day training
Yes
No
1-2 day training
4 day training
LiverAnalysis
LiverAnalysis
HeartAnalysis
HeartAnalysis
Slide presented at Global Iron Summit 2011 - With the permission of Juliano de Lara Fernandes
G-EXJ-1030713May 2012
Summary
51G-EXJ-1030713May 2012
Summary
● Iron overload is common in patients who require intermittent or regular blood transfusions to treat anaemia and associated conditions
● Analysing cardiac iron levels is important
– in β-thalassaemia major, cardiac failure and arrhythmia are risk factors for mortality
– in MDS, cardiac iron overload can have serious clinical consequences
– due to improved monitoring and management of iron overload over the last decade, 77% of patients have normal cardiac T2*1
● MRI: the method to rapidly and effectively assess cardiac iron loading
– T2* allows specific assessment of cardiac iron levels. The use of this convenient, non-invasive procedure has had a significant impact on outcomes in patients with cardiac iron overload1
– R2* is a simple calculation from T2* and has a linear relationship with cardiac iron concentration
1Thomas AS, et al. Blood. 2010;116:[abstract 1011]. 2Modell B, et al. J Cardiovasc Magn Reson. 2008;10:42-9.
G-EXJ-1030713May 2012
GLOSSARY OF TERMS
53G-EXJ-1030713May 2012
GLOSSARY
● AML = acute myeloid leukemia
● APFR = Atrialp peak filling rate
● BA = basilar artery
● ß-TM = Beta Thalassemia Major
● ß-TI = Beta Thalassemia Intermedia
● BM = bone marrow
● BTM = bone marrow transplantation
● BW = bandwidth
● CFU = colony-forming unit
● CMML = chronic myelomonocytic leukemia
● CT2 = cardiac T2*.
● DAPI = 4',6-diamidino-2-phenylindole
54G-EXJ-1030713May 2012
GLOSSARY
● DFS = = disease-free survival.
● DysE = dyserythropoiesis
● ECG = electrocardiography
● EDV = end-diastolic velocity
● EF = ejection fraction
● EPFR = early peak filling rate
● FatSat = fat saturation
● FAQ = frequently asked questions
● FDA = Food and Drug Administration
● FISH = fluorescence in situ hybridization.
● FOV = field of view
● GBP = Currency, pound sterling (£)
55G-EXJ-1030713May 2012
GLOSSARY
● Hb = hemoglobin
● HbE = hemoglobin E
● HbF = fetal hemoglobin
● HbS = sickle cell hemoglobin.
● HbSS = sickle cell anemia.
● HIC = hepatic iron concentration
● HU = hydroxyurea
● ICA = internal carotid artery.
● ICT = iron chelation therapy
● IDL = interface description language
● IPSS = International Prognostic Scoring System
● iso = isochromosome
56G-EXJ-1030713May 2012
GLOSSARY
● LIC = liver iron concentration
● LVEF = left-ventricular ejection fraction
● MCA = middle cerebral artery
● MDS = Myelodysplastic syndromes
● MDS-U = myelodysplastic syndrome, unclassified
● MRA = magnetic resonance angiography
● MRI = magnetic resonance imaging
● MV = mean velocity.
● N = neutropenia
● NEX = number of excitations
● NIH = National Institute of Health
● OS = overall survival
57G-EXJ-1030713May 2012
GLOSSARY
● pB = peripheral blood
● PI = pulsatility index
● PSV = peak systolic Velocity
● RA =refractory anemia
● RAEB = refractory anemia with excess blasts
● RAEB -T = refractory anemia with excess blasts in transformation
● RARS = refractory anemia with ringed sideroblasts
● RBC = red blood cells
● RF = radio-frequency
● RCMD = refractory cytopenia with multilineage dysplasia
● RCMD-RS = refractory cytopenia with multilineage dysplasia with ringed sideroblasts
● RCUD = refractory cytopenia with unilineage dysplasia
58G-EXJ-1030713May 2012
GLOSSARY
● RN = refractory neutropenia
● ROI = region of interest
● RT = refractory thrombocytopenia
● SCD = sickle cell disease
● SD = standard deviation
● SI = signal intensity
● SIR = signal intensity ratio
● SF = serum ferritin
● SNP-a = single-nucleotide polymorphism
● SQUID = superconducting quantum interface device.
● STOP = = Stroke Prevention Trial in Sickle Cell Anemia
● STOP II = Optimizing Primary Stroke Prevention in Sickle Cell Anemia
59G-EXJ-1030713May 2012
GLOSSARY
● T = thrombocytopenia
● TAMMV = time-averaged mean of the maximum velocity.
● TCCS = transcranial colour-coded sonography
● TCD = transcranial doppler ultrasonography
● TCDI = duplex (imaging TCD)
● TE = echo time
● TR = repetition time
● WHO = World Health Organization
● WPSS = WHO classification-based Prognostic Scoring System