palais du pharo, marseille, france, may 10, 2006 functional imaging and instrumentation group –...

Palais du Pharo, Marseille, France, May 10, 2006

Functional imaging and Instrumentation Group – Univ. Pisa

Department of Physics “E.Fermi”

University of Pisa

Institute of Clinical Physiology - CNR Pisa

Evaluation of the performance of the YAP-(S)PET scanner and its application in neuroscience

Nicola Belcari

Department of PhysicsUniversity of Pisa

http://www.df.unipi.it/~fiig/

Center of ExcellenceAmbiSEN - Univ. Pisa

YAP-(S)PET small animal scanner

Scanner configuration

Configuration: Four rotating heads

Scintillator: YAlO3:Ce (YAP:Ce)

Crystal size: 20 x 20 (2.0 x 2.0 x 25 mm3 each)

Photodetector: Position Sensitive PMT

Readout method: Resistive chain (4 channels)

FoV size: 4 cm axial 4 cm Ø

Collimators: (SPECT) Lead (parallel holes)

Head-to-head distance: 15 cm

Design

Latest configuration

Hardware

Performance

SensitivitySpatial resolution

Count rateImage quality

Scanner installed at the “Institute of clinical Physiology (IFC-CNR)” within the framework of the Center of Excellence AmbiSEN of the University of Pisa, Italy

Design


Hardware

Performance



YAP-(S)PET designUniversity of Pisa unit

The four heads are mounted on a rotating gantry and the detector spacing can be varied in the 10 cm – 25 cm range (only in our unit).

YAP:Ce matrix (4 4 cm2)400 finger crystals2.0 mm 2.0 mm 25 mm

HamamatsuR2486 (3” Ø)

Parallel hole lead collimator 2 cm thick.Holes: 600 m , 150 m septa

The detector head are equipped with the laser pointer.

The acquisition boards and the four HV units are mounted on the back of the gantry

Each acquisition board controls a pair of detectors. It performs the discrimination of the last dynode signals (and the timing coincidence when used in PET mode) using CFD. The four position signals from each tube are sampled and sent to a local PC for the acquisition. The boards now includes a pile-up rejection technique and faster ADC’s.

Animal Imaging

Performance: Sensitivity


Hardware

Performance



Design Measured sensitivity

PET:

High sensitivity energy window: ~23 cps/kBq @ CFOV (50-850 keV) (2.3%)

High resolution energy window:

~10 cps/kBq @ CFOV (50-420 keV) (1.0%)

SPECT:

Measured with 99mTc:

37 cps/MBq (140-250 keV)

Absolute sensitivity curve along the scanner axis in PET mode. The sensitivity is measured after energy cuts. The results are plotted against the actual position of the source along the axis. Two different curves are produced for different energy windows: 50-850 keV (high sensitivity) and 50-420 keV (high resolution).

Animal Imaging

Absolute sensitivity curve along as a function of the radial position of the source.

The PET system sensitivity is measured with a linear source placed inside a metal tubes. The measure is repeated five times with increasing wall thickness. The system sensitivity, averaged over the whole axial FOV, extrapolated from the accumulated sleeve measurements, is 1.1%.

Performance: PET spatial resolution


Hardware

Performance



Design Comparison of the radial, tangential, and axial FWHM of the reconstructed images, obtained with the FBP-2D (top left) and EM (bottom right) algorithms, using 3D-MS and SSRB (max dlim = 12) sinograms (50-850 keV energy window).

The spatial resolution is plotted against the radial offset.

FBP

EMUsing the high resolution energy window (50-420 keV) the spatial resolution is about 5% better.

We have used a 22Na point source of about 100 kBq.

Animal Imaging

Performance: PET volume resolution

The volume resolution is nearly constant using the SSRB(12) sinograms. Using EM it is well below 8 mm3 along the whole Field-of-View


Hardware

Performance



Design

Animal Imaging

Performance: Spatial resolutionDerenzo Phantom (PET)

2.5 mm

3.0 mm

1.5 mm

2.0

mm

EM 3D-MS50-850 keV

FBP 3D-MS50-850 keV

FBP 3D-MS50-450 keV

1.5

mm

2.0

mm

The rods of the Derenzo phantom were filled with 300Ci of a 18F solution and scanned for 75 min. Both EM and FBP (ramp filter) reconstructions were used on a 0.50.52 mm3 voxel space. Sinograms were build using to high sensitivity energy window (50-850 keV).


Hardware

Performance



Design

Animal Imaging

Performance: SPECT spatial resolution


Hardware

Performance



DesignImage of a glass capillar filled with about 1 mCi of a 99mTc solution and scanned for 30 min.

Transaxial

Axial

FBPEM 9 it.

(Automatic termination*)

“A.MOTTA, C.DAMIANI, DEL GUERRA A., G.DI DOMENICO, G.ZAVATTINI. (2002). Use of a fast deconvolution EM algorithm for 3-D Image Reconstruction with the YAP-PET tomograph. COMPUTERIZED MEDICAL IMAGING AND GRAPHICS. vol. 26, pp. 293-302

Transaxial resolution

(FWHM)

3.8 mm 2.75 mm

The resolution is constant over the whole FOV

Animal Imaging

Performance: Spatial resolutionDerenzo Phantom (SPECT)

The rods of the Derenzo phantom were filled with 5mCi of a 99mTc solution and scanned for 60 min. Both EM and FBP (ramp filter) reconstructions were used on a 0.50.52 mm3 voxel space. Sinograms were build using 140-250 keV energy window.

3 mm

2.5 mm 2 mm

1.5 mm

1.2 mm

3 mm

2.5 mm 2 mm

1.5 mm

1.2 mm

FBP EM 50 it.


Hardware

Performance



Design

Animal Imaging

Performance: PET count ratemethod

The count rate performance in PET mode was estimated in terms of noise-equivalent counting rate (NEC) for a mouse sized phantom. The phantom was filled with a solution containing 18F and scanned over 5 half-lives. The true (Rtrue) and scattered (Rscatt) counting rates were calculated from the measured prompt (RTOT) and random (Rrand) counting rates.


Hardware

Performance



Design

SF25 mm

10 mm

70 mm

Picture and size of the mouse sized phantom used for scatter fraction and count rate evaluation.

Aligned and summed projections of sinograms from a 1 cm off-center line source in a “mouse sized” scatter medium (7 cm long, 2.5 cm Ø). The scatter events (yellow) are estimated by fitting the projection tails up to ±7 mm from the center.

The measured scatter fraction is 21.7% with a 50-850 keV energy window

Scatter fraction

true

scatter

Animal Imaging

Performance: PET count rateOld vs. FAB


Hardware

Performance



Design

where the Rrand has been measured using delayed coincidence window technique.

SF)(1)R-(RR randTOTtrue

)() SF randTOTscatt R-(R R

randscatttrue

2true

NEC RRR

R R

The NEC counting rates was then

calculated using the equation:

For this phantom, a wide open energy window of 50 to 850 keV combined with a 14 ns timing window provides a “maximum” peak NEC of 50 kcps at an activity of about 900 Ci (33 MBq) corresponding to a coincidence count rate of about 135 kcps

Animal Imaging

The maximum count rate is about 180 kcps corresponding to an activity in the phantom of about 2 mCi

Performance: PET count ratePile-up rejection effect


Hardware

Performance



Design

For this phantom, a wide open energy window of 50 to 850 keV combined with a 14 ns timing window and the pile-up rejection, provides an “effective” peak NEC of 30 kcps at an activity of about 600 Ci (22 MBq) corresponding to a coincidence count rate of about 100 kcps.

Pile-up rejection

Activity RNEC RTOT Dead time loss Pile-up loss

600 Ci 30 kcps 66 kcps 13 % 40%

300 Ci 26 kcps 50 kcps 9 % 23 %

Animal Imaging

Performance: Image qualityNEMA I.Q. Phantom

8 mm

1 mm

2 mm

4 mm

3 mm

5 mm

30 mm


Hardware

Performance



Design

Drawing and picture of the NEMA Image Quality phantom for small animal PET scanners. The interior is has been filled with:PET mode: 600Ci of a 18F solution and scanned for 30 min. SPECT mode: 5 mCi of a 99mTc solution and scanned for 60 min. Both EM and FBP (ramp filter) reconstructions were used on a 0.50.52 mm3 voxel space.

Animal Imaging

Performance: Image qualityNEMA I.Q. Phantom images (PET)


Hardware

Performance



Design

FBP Post normalized

EM (50 it) Post normalized

FBP Post-normalizedEM (50 it.) Post normalized (E.W. 50-850 keV)

Animal Imaging

Performance: Image qualityNEMA I.Q. Phantom images (SPECT)

FBP

FBP

(E.W. 140-250 keV)Latest

configuration

Hardware

Performance



Design

Animal Imaging

EM coll. (50 it.)

EM coll. (50 it.)

Harderian glands

Cerebral cortex

Neostriatum

Thalamus

Olfactory bulbs

Salivary glands

Inferior colliculus

Cerebellum

Eye ball

Transaxial sections (0.25 mm x 0.25 mm x 2.0 mm)

Animal imaging: Brain metabolism in rat with 18F-FDG (PET)


Hardware

Performance



Design

Animal Imaging

Rat threated with receptor blockingNormal Rat

Transaxial section

Horizontal section

Transaxial section

Horizontal section

Animal imaging: dopamine receptors in rats with 18F-Fallypride (PET)

Rat pre-treated with intraperitoneal injection of 50 mg/(kg body weight) amisulpride in order to block the binding of the 18F Fallypride

All the animals were anesthetized with chloralhydrate 7%, injected via a lateral tail vein with 37 MBq of 18F-Fallypride and immediately scanned. EM reconstruction: 40 iterations.

Normal rats were compared with rats with receptor blocking by monitoring the activity in the striatum, using a high-affinity dopamine D2 receptor ligand 18F-Fallypride


Hardware

Performance



Design

Animal Imaging

In collaboration with University of Mainz, Germany

Animal imaging: rat model of Huntington’s disease with 11C-Raclopride (PET)

Surgery

Male Wistar rats weighting 300 g were injected icv in the left

striatum with 210 nmol of QA solution and in the right striatum

with PBS 0.1 mol/L. Stereotaxic coordinates: AP=+ 1.5, L=+

2.6, V=-7.0 mm from the Bregma, according to the atlas of

Paxinos and Watson.

Coronal Axial

Coronal

Coronal

Axial

Axial

L

Autoradiography

Eight and thirty days after the surgery respectively, two rats

were injected with 130 Ci of [11C]Raclopride and sacrificed

after 30 minutes. The brain was rapidly removed and coronal

section of 2 mm-thickness were performed on unfrozen tissue

using a brain matrix. Acquisition for 100 minutes with Cyclone

Storage Phosphor System .

Evolution of a monolateral lesion QA induced

L

L


Hardware

Performance



Design

Animal Imaging

In collaboration with ospedale S. Raffaele, Milan, Italy

Animal imaging: mouse model of Parkinson disease with 123I-DATScan

(SPECT)

Pre-treatment with potassium perclorate (thyroid block).Tail-vein injection of about 100 Ci of 123I-FP-CIT.Anesthesia: i.p. injection of a mix of ketamine and xylazine or phentobarbital alone.SPECT images starting 3 hrs after the radiopharmaceutical injection.

EM reconstruction (20 iteractions)

after background correction with dual energy windowing


Hardware

Performance



Design

Animal Imaging

SPECT images of asymptomatic EnHT mouse (20 g)

Harderian glands

Striatum

Energy windowing subtraction

Pre-correction Corrected

123I SPECT data are contaminated by an high background due to high energy (>500 keV) gamma rays that penetrates the collimator.

Sinogram data are corrected by backgroud subtraction using a dual

energy windowing technique Example: Derenzo Phantom

Summary

• Some improvements have been done at both hardware and software level.

• The count rate capability (NEC) and image quality have been improved

– The maximum count rate is 180 kcps– The peak NEC is 50 kcps (without pile-up rejection) corresponding

to an acquisition rate of 100 kcps

• In PET mode the scanner shows a volume resolution 8 mm3 over the whole FOV using EM and SSRB(12) sinograms and an absolute sensitivity of 2.3% at the center of the FOV (50-850 keV energy window).

• In SPECT mode the scanner shows a spatial resolution ~2.7 mm (using EM) and an absolute sensitivity of 37 cps/MBq (140 keV-250 keV) over the whole FOV.

• The performance of the YAP-(S)PET are adequate for both PET and SPECT molecular imaging application in neuroscience on small animals.

http://www.df.unipi.it/~fiig/

Questions?Th

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ou

!

Addendum

HardwareFAB

A novel acquisition board has been developed

• This new board called FAB (Fast Acquisition Board) includes:

– Faster ADC’s (to improve count rate)

– A novel electronic pile-up rejection circuitry (to improve image quality)

– More on-line counters (to better display what’s going on)

• Additional refinements have been made on the pre-Amp boards


HardwareSoftware

Performance



Image of the novel FAB

Design

Animal Imaging

Hardware Old acquisition board vs. FAB


Hardware

Performance



Left: plot of the Acquisition count rate vs. the real number of detected coincidences for the old and the new FAB acquisition boards

Bottom: plot of the Acquisition count rate vs. the Activity in the NEMA mouse like phantom for count rate performance evaluation.

• 7.5% dead time loss vs 20% @ 20 kcps

• 10% dead time loss vs 35% @ 40 kcps

• 12.5% dead time loss vs 50% @ 80 kcps

• 14% dead time loss vs 60% @ 120 kcps

Design

Animal Imaging

Count rate

Software / 1Sinogram Normalization

The sinogram should be normalized

(i.e. equalize the LOR relative efficiency)

• The normalization starts from a planar aquisition of a uniform planar source.• The acquisition has two views, each LOR is filled with the same activity.

• Two kinds of normalization are now possible: – Pre-normalization (LOR by LOR)– Post-normalization (PVI sinogram)


HardwareSoftware

Performance



Design

• A big syringe (15 mm ) has been filled with a 18F solution. Approximately 700 Ci, were present in the FOV.

• The sinograms were built using 3D-MS with and without the Post-normalization.

• The Post-normalization improves the uniformity the center of the transaxial FOV.

FBP 3D-MSNo normalization

FBP 3D-MSPost-normalization

Software / 1Sinogram Normalization

FBP 3D-MSNo normalization

FBP 3D-MSPost-normalization

EM 3D-MSPost-normalization


Hardware Software

Performance



Design

• Two small syringes (4 mm ) have been filled with a 18F solution diluted by a factor of two one respect the other. Approximately 300 Ci, and 150 Ci were present in the two syringes respectively.

• The sinograms were built using 3D-MS with and without Post-normalization.

• Pre-normalization gives similar results.

• The Post-normalization improves the axial uniformity especially at the borders of the FOV

No- and Post-normalization comparison of the measured axial intensity (FBP reconstruction)

Software / 2SSRB Sinograms

• The SSRB (Single Slice Re-Binning) is a rebinning technique where the skewed LOR’s (i.e. having a non zero component along the scanner axis) are re-binned on 2D sinograms by simply straightening the LOR’s on the mid-span plane.


Hardware Software

Performance



Design

The 2D sinograms can now be built by also applying a constraint on the maximum inclination of the LOR (expressed as max dlim) to be used or not.

The 3D-MS sinogram is actually a SSRB sinogram with no limitation while the 2D sinogram is a special case of the SSRB where max dlim = 0

dlim

= 1

3

• Applying a limitation on max dlim helps in reducing the axial resolution blurring at the borders of the transaxial FOV.

• A limitation of the SSRB is a reduction of the sensitivity at CFOV. For example using SSRB(12) the absolute sensitivity at CFOV is reduced by 35% but the system sensitivity is reduced by 12% only.

Other applications

Rat with induced Ipotyroidism

Normal Rat

Normal rats (Wistar) were compared with rats with induced Ipotyroidism in terms of brain glucose consumption (FDG). The effect of the threatment with T3 has been also studied. The rats with induced Ipotyroidism shows a strongly reduced uptake in the harderian glands

Other applications

Rat with brain glioma

Normal Rat

Normal rats (Wistar) were compared with rats with a brain glioma in terms of brain glucose consumption (FDG). The technique is able to identify the size and the position of the tumor in the brain.

EM (50 it.)

EM (50 it.)

palais du pharo, marseille, france, may 10, 2006 functional imaging and instrumentation group –...

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