Transcript ISS-NIH-f-1 - INFN Gruppo Collegato Sanit&#224

Novel High resolution SPECT Instrumentation and
Techniques for Molecular Imaging of Small Animals
F. Garibaldi - ISS-NIH, Rome, 4-6 June 06
Molecular imaging with radionuclides :the in vivo characterization and
measurement of biologic processes at the cellular and molecular level
It sets forth to probe the molecular
abnormalities that are the basis of
disease rather than to image the end
effects of these molecular alterations
The rat and mouse host a large
number of human diseases. Therefore
one can study disease progression and
therapeutic response under controlled
conditions
PET (microPET) cannot attain the
needed performances !
MRI doesn’t have the needed
sensitivity
Collaboration between ISS, JHU(B. Tsui),
Jefferson Lab (S. Majewski)
specific task
-detecting vulnerable plaques in mice
what you need
-high resolution high sensitivity detectors
key parameters:
- SNR
- FOV
- Sensitivity
- Spatial Resolution
- simulations, prel. measurements
Summary and outlook
Molecular Imaging Modalities
Ultrasound
CT
Optical
A
F
(Bioluminescence, fluorescence)
Structure
0.1 mm
Doppler
Unique !!
A
M
Topography
µm to mm
~103 cells
 quantitative
A Tissue Density, Z
20-50 µm
MRI
PET/SPECT
F
A
F
M
H Concentration
0.1 mm
BOLD, DCE
-galactocidase
0.1 µmole H / µmole 31P
M
Radiotracer
~1-2 mm
<10-12 mole
= quantitative
γ Imaging: Single Photon Detector Module
1.Collimator
Only gammas that are
perpendicular to imaging
plane reach the detector
Patient injected with
radioactive drug.
Drug localizes according
to its metabolic
properties.
Gamma rays, emitted by
radioactive decay, that
exit the patient are
imaged.
2.Scintillator
Convert gammas to
visible light
3.Photomultiplier
Convert light to
electrical signal
4.Readout Electronics
Amplify
electrical
signal and interface to
computer
5.Computer decoding
procedure
Elaborate signal and
gives image output
High Resolution High Sensitivity Detectors
key parameters
SNR (and contrast)
FOV
SNR 
(spatial resolution)
S  BKG
S
IC 
S = counts in ROI,
Max = max. counts
in tumor ROI
BKG = background
they are correlated


Max  BKG
Max
N channel
X
Gamma Emission X position
c X
i
i 1
N channel
i
c i  ith channel signal
X i  ith X channel position
 ci
i 1
X 
 Xi
N p.e.

FWHMX i
 R i  FWHMX 
N p.e.
Light Spread Function (LSF)
DRF n(r,z) 


(x,y)PSF (x  r)2  y2 ,z


 dxdyP
1/ 2
FWHM = 7.4
mm
FWHM = 5.4
mm
energy resolution plays only a secondary additional role in imaging breast under compression
Diffusive Wall
Absorbing
Wall
Important parameters for detectability/visibility
efficiency
- SNR
detector and collimation
time (and modality)
uptake (radiopharmacy)
scintillator
- Contrast
detector intrinsic properties
pixel dim/n.of pixels
modality (compression)
electronics, DAQ
spatial
resolution
. Uniformity of p.h.response
(affecs the overall en res.
and the energy window sel.)
l)
CsI(T
Bialkali PMT
Bialkali PMT
fotofraction
Importance of pixel identification
STD[Xrec-Xreal] v s Anode Size for CsI(Tl) scintillator
1.4
pitch
pitch
pitch
pitch
STD[Xrec-Xreal] (mm)
1.2
1.0
0.8
0.6
0.4
mm
mm
mm
mm
1
0.8
0.6
0.4
0.2
0
0
1
2
3
4
5
6
7
8
Anode Size (mm)
good pixel identification is fundamental for correct digitization affecting spatial resolution and contrast
C8 strips
M16 (4 x 4) mm2
M64 (2 x 2) mm2
QuickTime™ and a
T IFF (Uncompressed) decompr essor
ar e needed to see this pictur e.
Projective coordinate
electronics
1024 ch, 2 KHz
Under study
4096 Ch. -> 8192 Ch. (10-20 kHz)
tumors: (5, 6, 7, 8,9,10,12)
uptake 1:10; breast 6 cm
measurements
NaI(Tl) 1.5 pitch;
H8500 (6x6 mm2)
6 mm
SNR vs tumor dimension(10:1-breast 6cm-NaI 1.0-H8500(6x6mm2)
8 mm
20
18
QuickTime™ and a
TIFF (U ncompressed) decompressor
are needed to see this picture.
16
7 mm
14
SNR
12
10
H
X (H9500)
8
6
4
2
0
4
5
6
7
8
9
10
t(mm)
11
12
6 mm tumors
13
visible
measurements confirm simulation
smaller scintillator pixel, higher SNR
NaI(Tl) 1.3 pitch;
H8500(6x6 mm2)
NaI(Tl) 1.2 pitch
H9500 (3x3 mm2)
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
but
anode pixel has to be small
tum 8 mm
Performances not good enough for imaging biological process in vivo in
small animals (mice)
man
rat
Man
Rat
Mouse
Body weight
~70 kg
~200 g
~20 g
Brain
~105 mm
~10 mm
~6 mm
Heart
~300 g
~1 g
~0.1 g
Aorthic cannula
~ 30 mm
1.5 – 2.2 mm
0.9-1.3 mm
(0.5 mm)
Trying to Image apoptosis by proper tracer (e.g.99mTcINIC-Annexin-V)
Geant 4 simulation
detector area: 100 x 100 mm2
aorta: ~ 2 mm diameter
plaque size: 0.5 x 1 x 4 mm3
spatial resolution: ~ 500 m
system sensitivity: ~ 10 cps/Ci
1000 counts/view/resol.elem.
1 plaque = 10 mCi,10resol.elem.
- pixellated CsI(Tl) (0.8 - 0.4 mm pitch)
- LaBr3 continuous (3 mm thick, different
surface(s) treatment(diffusive vs absorptive)
- 6 x 6 mm2, 3 x 3 mm2, 1.5 x 1.5 mm2
(PMT anode pixel size)
Summary of CsI(Tl), pixellated
0.6 mm pitch H9500
0.6 mm pitch Burle
What about CsI(Na) ??
LaBr3 to be carefully evaluated
Scaling down (100 mm, 0.8 mm --> 50 mm, 0.4 mm)
1/4 of detector area,
1/4 number of channels
but
0.4 mm is very small !!
mouse doesn’t scale !
simulation summary
snr calculation
sensitivity too small

but
multiply by ~ 4 (multipinhole) x 4(8) ( n. of modules)
snr = 30 ( 60 ) ===> plaque “visible”
sensitivity
smaller than
required
There are decoding patterns G allowing:
A  G = dthen
A  G = Ô, in fact
Coded apertures
Ô = R  G = ( O × A )  G = O * (A  G) = O * PSF
Submillimeter spatial resolution
(FWHM=0.93 mm) AND
recostruction possible in a deepth of
focus as large as large as 4 cm !!
High sensitivity (~850cps/MBq)
30 time pinhole already obtained
QuickTi me™ and a
QuickTi me™
and a
TIFF (U ncompressed)
decompressor
TIFFneeded
(U ncompressed)
are
to see thisdecompressor
picture.
are needed to see this picture.
[1] F. Garibaldi et al, Small Animal Imaging by Si ngle Photon
Emission Using Pinhole and Coded Aperture Collimation,
IEEE Trans Nucl Sci, 52 (3), (2005), 573-579.
QuickTi me™ and a
TIFF (U ncompressed) decompressor
are needed to see this picture.
F. Cusanno et al. NIM A
Both spatial resolution and
sensitivity still to be improved
Smaller scintillator pixels (0.8 --> 0.6 mm) ==> smaller photodetector anode pixels
Measurements
60Co
source, 122 keV
NaI(Tl) 1.25 pitch
H8500 (6 x 6 mm2)
CsI(Tl) 1.0 pitch
CsI(Tl) 1.25 pitch
H9500 (6 x 6mm2)
H9500 (3 x 3mm2)
measurements confirm simulations: small anode pixel is needed for small scintillator
pixel (0.8 --> 0.6 mm --> high number of channels 1024 for 1 module! )
LaBr3 continuous 1.5 mm thick + H9500 (3 x 3 mm2 anode); 3 mm thick + H8500(6 x 6 mm2)
1.5mm thick LaBr3 attached to a H9500 PSPMT
Image of a 0.25mm slit. Chipped edge
seen at left. Non-uniformities to correct.
Measured energy resolution
~ 8% FWHM @122 keV
Projection of the image of the slit.
FWHM = 0.65mm
Mcarlo FWHM = 0.615
3 mm mm thick LaBr3 attached to a H8500 PSPMT
Active area
0.75 mm FWHM
Dead area
1.4 mm FWHM
Mcarlo FWHM = 0.8
Preliminary pinhole SPECT reconstruction results from the CsI detector
Images are displayed as MIP (maximum-intensity-re-projections) animations
Please use slide show mode to see the animation
2 point sources
Flood image
APOE mouse (kidneys shown)
Sample
projection
image
Conclusions
A solution for this challenging problem exists:
- good results with CsI(Tl) 1 mm pitch + H9500 100 pixels, spatial resolution
0.53 mm - 0.46 mm, FOV=33-25,

(22-39) cps/MBq
improvements needed?
scaling down (50 x 50 mm2, 0.4 mm pitch, Burle photodetector (3x3 mm2)
->more compact, much less expensive
- 100 x 100 mm2 CsI(Tl) 0.8 (0.6) mm pitch with individual readout
- careful evaluation of LaBr3 option (the advantage is better energy resolution
(very important if multilabeling shows to be possible and useful)
- Fov, surface treatment, thickness, availability, cost
- decision to be taken on the base of SNR obtained with measurements (phantoms)
Measurements for CsI(Na) 0.4 - 0.6 mm pitch, LaBr3 3 mm thick
10 x 10 cm2 vs 5 x5 cm2 (scaling down) (tomographic reconstruction will be decisive)
Final layout on two steps next two years
(if funding allows)
Invited talks
Invited talks a Congressi Internazionali
1.F. Cusanno. “High Resolution, High Sensitivity detectors for Molecular imaging with Radionuclides: the Coded
Aperture option”. Milos (Grecia). Imaging technologies in Biomedical Sciences. September 2005
2. F. Garibaldi. “High Resolution, High Sensitivity Detectors”, Advanced Molecular Imaging Techniques in the
Detection, Diagnosis, Therapy, and Follow-Up of Prostate Cancer, Rome, 6-7 December
3. Magliozzi ML et al “High Resolution, High Sensitivity Detectors for Molecular Imaging of Small Animals and
Tumor Detection”. International Conference of Advanced Detectors. Como (Italy), October17-21, 2005
4. F. Garibaldi, “Molecular imaging: high resolution detectors for early diagnosis and therapy of breast cancer”.
Milos (Grecia). Imaging technologies in Biomedical Sciences. September 2005
5. "Molecular Breast Imaging: first results from Italian National Health Institute clinical trials", to be presented
at the International Conference "Fist European Conference on Molecular Imaging Technology (EUROMEDIM2006)”
Marseille, France, 9 - 12 May 2006
6. E. Cisbani, “Imaging with radionuclides: a powerful means for studying biological processes in vivo", Fist
European Conference on Molecular Imaging Technology (EUROMEDIM2006)", Marseille, France, 9 - 12 May 2006
- Cuba ?
Publications
1.
F. Garibaldi et al. “A PET scanner employing CsI films as photocathode”, Nucl. Instr. Meth., 2004, A525, 263267.
2.
F. Garibaldi et al. “Novel design of a parallax free Compton enhanced PET scanner”, Nucl. Instr. Meth.,
2004, A525, 268-274.
3.
R. Pani, M.N. Cinti, F. Cusanno, F. Garibaldi et al“Imaging detector designs based on Flat panel PMT”, Nucl.
Instr. Meth., 2004, A527, 54-57.
4.
F. Cusanno et al. “Molecular imaging by single-photon emission”, Nucl. Instr. Meth., 2004, A527, 140-144.
5.
F. Cusanno et al. “Preliminary Evaluation of Compact Detectors for Hand-Held Gamma Cameras”, Physica
Medica, 2004, XX (2), 65
6.
Pani R. Cinti, M.N., Cisbani, E.; Colilli, S.; Cusanno, F.; De Vincentis 6.
Preliminary study of metabolic
radiotherapy with 188-Re via small animal imaging, A. Antoccia, G. Baldazzi, M. Bello, D. Bernardini, P.
Boccaccio, D. Bollini, F. de Notaristefani, F. Garibaldi, G. Hull, U. Mazzi, G. Moschini, A. Muciaccio, F.-L.
Navarria, V. Orsolini Cencelli, G. Pancaldi, R. Pani, A. Perrotta, M. Riondato, A. Rosato, A. Sgura, C.
Tanzarella, N. Uzunov, M. Zuffa Nuclear Physics B, Volume 150, January 2006, Pages 411-416
7.
Small animal imaging by single photon emission using pinhole and coded aperture collimation, Garibaldi, F.;
Accorsi, G.; Fortuna, A.; Fratoni, R.; Girolami, B.; Ghio, F.; Giuliani, F.; Gricia, M.; Lanza, R.; Loizzo, A.;
Loizzo, S.; Lucentini, M.; Majewski, S.; Santavenere, F.; Pani, R.; Pellegrini, R.; Signore, A.; Scopinaro, F.;
Veneroni, P.; IEEE Transaction on Nuclear Science, Volume 52, Issue 3, Part 1, June 2005 Page(s):573 – 579
8.
New Devices for Imaging in Nuclear Medicine, Cancer Biotherapy & Radiopharmaceuticals, 19(1), 121-128,
2004
9.
A PET scanner employing CsI films as photocathode, Nucl Instr Meth A525, 2004, 263-267
10.
Novel design of a parallax free Compton enhanced PET scanner Nucl Instr Meth A525, 2004, 268-274
11. A study of intrinsic Crystal-pixel light-output spread for discrete scintigraphic imagers modeling, Scafe, R.; Pellegrini, R.;
Soluri, A.; Montani, L.; Tati, A.; Cinti, M.N.; Cusanno, F.; Trotta, G,Pan Pani, R.;Garibaldi,F.,IEEE Transaction on Nuclear
Science, Volume 51, Issue 1, Part 1, Feb. 2004 Page(s):80 - 84
12. Custom breast phantom for an accurate tumor SNR analysis, Cinti, M.N.; Pani, R.; Garibaldi, F.; Pellegrini, R.; Betti, M.;
Lanconelli, N.; Riccardi, A.; Campanini, R.; Zavattini, G.; Di Domenico, G.; Del Guerra, A.; Belcari, N.; Bencivelli, W.; Motta,
A.; Vaiano, A.; Weinberg, I.N.; IEEE Transaction on Nuclear Science, Volume 51, Issue 1, Part 1, Feb. 2004 Page(s):198 - 204
Publications
- Molecular imaging by single-photon emission”, Nucl. Instr. Meth., 2004, A527, 140-144.
- Preliminary Evaluation of Compact Detectors for Hand-Held Gamma Cameras”, Physica Medica, 2004, XX (2),
65-70
- Small Animal Imaging by Single Photon Emission Using Pinhole and Coded Aperture Collimation”, IEEE Tran Nucl
Sci, 2005, 52(3), 573-579.
- Tumor SNR Analysis in Scintimammography by Dedicated High Contrast Imager”, IEEE Trans Nucl Sci, 2003,
50(5), 1618-1623
-Custom breast phantom for an accurate SNR analysis, IEEE Trans. N.S., Vol 51, N.1 Feb. 2004
- Molecular imaging: high resolution detectors for early diagnosis and therapy monitoring of breast cancer,
To be published on NIM, Milos
-High Resolution, High Sensitivity Detectors for Molecular Imaging with Radionuclides: the Coded Aperture Option,
to be published on NIM
- Euromedim Francesco
- Euromedim Evaristo
- Euromedim Carrato
-A. Dragone
1.
“A PET scanner employing CsI films as photocathode”, Nucl. Instr. Meth., 2004, A525, 263-267.
2.
“Novel design of a parallax free Compton enhanced PET scanner”, Nucl. Instr. Meth., 2004, A525, 268274.
3.
“Imaging detector designs based on Flat panel PMT”, Nucl. Instr. Meth., 2004, A527, 54-57.
4.
“Molecular imaging by single-photon emission”, Nucl. Instr. Meth., 2004, A527, 140-144.
5.
“Preliminary Evaluation of Compact Detectors for Hand-Held Gamma Cameras”, Physica Medica,
2004, XX (2), 65-70.
6.
“Small Animal Imaging by Single Photon Emission Using Pinhole and Coded Aperture Collimation”,
IEEE Tran Nucl Sci, 2005, 52(3), 573-579.
7.
Milos code apertures
8.
Milos breast?
9.
Prostate Rome, in preparation
10.
Invited talks at Euromedim (titoli anche se non so se mettere il breast)
11.
Deleo et al (la PET del CERN sottomesso a NIM)
12.
altri lavori (recenti) di PET CERN)
13.
lavori dei nostri amici del pin diodes (IEEE CD?? )
14.
altra roba recente di Pani in cui ha messo solo me?
15.
Como M.Lucia
Invited talsk (presentazione a congressi):
1.
2.
3.
4.
5.
6.
7.
Milos 2005
Milos 2005
Prostate Conference
Euromedim a Maggio
What else? (dal 2004)?
Como MLuci
Cuba?
Positron
Emission
Tomography
microPET
•
Source
•
Image Plane
511
511

E 0 E 0  E re
Photon direction is determined
within conical ambiguity
cos  1
•
1st Detector
Detection
coincident
events
between two detectors
Compton scatter equation relates
scatter angle and Eo and Ere
Imaging
Distance

2nd Detector
10 cm
Scattered
 - Rays
Compton Probe
High-Sensitivity Coll.
High-Resolution Coll.
Internal Compton Probe
Efficiency
1.8e-3
1.11e-4
4.00e-5
Resolution
2.47mm
15.9mm
10.5mm