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Multimodality imaging: prostate cancer diagnosis and follow up by TOF-PET &
MRI/MRSF. Garibaldi – INFN Roma and ISS Why do we need a dedicated multimodality system dedicated to prostate
imaging?
Potential design concept for prostate-specific PET Imaging
Background issue: the role of TOF-PET
PET – TOF design concept
The role of MRI and MRS
Multimodality challenge(s)
Silicon Photomultipliers (SiPm)
Summary and outlook
F. Garibaldi1, E. Cisbani, S. Colilli, F. Cusanno, R. Fratoni, F. Giuliani, M. Gricia, M. Lucentini, M.L. Magliozzi, F. Santavenere, S. Torrioli
Italian National Institute of Health and INFN Rome, ItalyItalian National Institute of Health – Rome
R. De Leo, E. NappiUniversity of Bari and INFN Bari
F. Giove, B. Maraviglia, F. Meddi,
Physics Department, University la Sapienza, Rome
S. Majewski, J ProffitJefferson Lab, Newport News, USA
Advanced molecular imaging techniques in the detection, diagnosis, therapy, and follow-up of prostate cancer
Rome - December 2005
Advanced molecular imaging techniques in the detection, diagnosis, therapy, and follow-up of prostate cancer
F. Garibaldi, Italian National Insitute of Health and INFN Rome1, gr. Sanita’
Workshop on Compton Camera Applications to Bio-medical
Imaging
Mattinata 5-7 September 2002
Frontiers in Imaging science: high performance detectors for vascular disease (brain and heart) imaging based on the latest developments in scintillators, photodetectors, and solid state materials
Rome - ISS - 12,13,14 November 2006
55/100,000 55/100,000 per year in Europe per year in Europe
90009000 new cases/year in Italynew cases/year in Italy
Prostate cancer is the Prostate cancer is the most common cancermost common cancer and andthe the second leading causesecond leading cause of cancer death in of cancer death in
Italian menItalian men
INCIDENCEProstate Cancer Diagnosis: Prostate Cancer Diagnosis: MRIMRI
PSA levelSensitivit
ySpecificit
y
1,1 ng/ml 83,4 38,9
1.6 ng/ml 67 58,7
2.1 ng/ml 52,6 72,5
2.6 ng/ml 40,5 81,1
3.1 ng/ml 32,2 86,7
4.1 ng/ml 20,5 93.8
6.1 ng/ml 4,6 98,5
8.1 ng/ml 1,7 99,4
10.1 ng/ml
0,9 99,7
Any Cancer (n.: 1225) VSAny Cancer (n.: 1225) VSNo Cancer (n: 4362 pts)No Cancer (n: 4362 pts)
Thompson IM, JAMA 2005
PSA: Sensitivity and Specificity
0
50
100
150
200
<4 4 e 10 10 e 20 >20
Distribuzione casi per range di PSA
No K
K
PSA remains an important prognostic markers of the biological potential of newly diagnosed prostatic cancer and the best marker to evaluate treatment outcome.
It will be a challenge to the medical community to change the long- held notion that there is a “normal” PSA value at which to recommended biopsy.
PSA proxy as Age, PSA Density, PSA velocity, Free PSA, ACT-PSA, BPSA can help the physician in the decision making process.
Future markers or tools for the early detection of clinically significant prostate cancer and to avoid unnecessary biopsy are strongly needed.
Cutoff?
Recent INDICATIONS for BIOPSY
• Abnormal PSA level
• DRE + false negative
false positive
BIOPSY
• TRUS (hypoechoic lesion)
• normal DRE and PSA
Not necessarily
BIOPSY
PROSTATE CANCER
PSA
DRE TRUS
CONCLUSION
I level
II level
BIOPSY
MRI and Spectroscopy
State of Art
*Catalona WJ, Smith DS ,Ornstein DK et al. JAMA 277: 1452-1455, 2004**Langer JE et al. Semin Roentgenol 34: 284-294,,2004
DRE
PSASensibility
PSA level ≤ 4.0 ng/ml 67.5 - 80% PSA level > 4.0 ng/ml 60 - 70%
TRUS
Normal DRE and PSA
< 4.0 ng/ml
Do not exclude prostate cancer*
DIAGNOSTIC PITFALLS• 30% palpable lesions at DRE
False Positive high rate• 20% hypoechoic lesions
are truly malignant**
EARLY DIAGNOSIS PITFALLS EARLY DIAGNOSIS PITFALLS
Prostate Cancer Diagnosis: MRI
Prostate Cancer
MRS: the role of CHOl
CHOl PET can differentiate aggressiveness (G<7 vs G>7)
Single Photon:111In-ProstaScint
Prostate
Rectum
Collimator
GammaImager
Source
Image Plane
1st Detector
2nd DetectorScatteredγ - Rays
N. Clinthorne. MichiganSingle photon Compton camera
Radinuclides Single photon
Internal PET prostate probe proposed by Levin and presented also by Moses that works in coincidence with an external PET detector. This figure is from presentation by Moses.
Device proposed by Clinthorne. and Majewski. Full ring external PET detector provides more complete sampling and can be used with more conventional PET protocols
Radionuclide imaging (PET)
potential of a multimodality dedicated device - Screening ?
- Reducing rate of false negative?
- Reducing rate of false positives?
- Staging?
- Detecting recurrence?
- Monitoring therapy?
requirements for radionuclide imaging
- radiotracer (high specificity)- high sensitivity- practical consideration, cost
high SNR
-
drawback of the standard PET
- detectors far away from prostate- poor spatial resolution (6 – 12 mm)- poor photon detection efficiency (<1%)- activity ouside the organ -> poor contrast resolution- relative high cost per study
design concept: a small rectal prostate probe (+ external panel detectors) compatible with MRI scanners
- close proximity imaging- improved spatial resolution and photon detection imaging- mobile- lower cost device - > lower cost study
TOF - PET
W. Moses NSS-MIC 2008
TOF issues
W. Moses NSS-MIC 2008
Proposed Side-Coupled Design
Proposed Geometry(Side-Coupled Crystal)
ScintillatorCrystal
PMT
PMT
Shorter Optical Path Length & Fewer ReflectionsShorter Optical Path Length & Fewer Reflections
Conventional Geometry(End-Coupled Crystal)
384 ps(543 ps coinc.)
218 ps
W. Moses NSS-MIC 2008
W. Moses NSS-MIC 2008
convTOF SNRx
DSNR
c
tx
2
Time Resolution
(ns)
x
(cm)
SNRimprovement(20 cm object)
SNRimprovement(40 cm object)
0.1 1.5 3.7 5.2
0.3 4.5 2.1 3.0
0.5 7.5 1.6 2.3
1.2 18.0 1.1 1.5
Time-of-Flight and SNR
DOI mandatory
25
30
35
40
45
50
0.95 1 1.05 1.1 1.15 1.2 1.25 1.3
Decay Time (ns)
Relative Light Output
Optimization: LSO CompositionOptimization: LSO Composition
Ca-Doping Gives High Light Output & Short Ca-Doping Gives High Light Output & Short
Normal LSO High Light Out
Short The Good Stuff!
= Ca-doped
0.1%0.2%0.4%
0.3%
• Ca-Doping Gives Good Timing Resolution• ~15% Improvement Over Normal LSO
• Ca-Doping Gives Good Timing Resolution• ~15% Improvement Over Normal LSO
150
160
170
180
190
200
210
220
230
80 100 120 140 160 180 200Time Resolution (ps fwhm)Initial Intensity (I
0)
Normal LSO
Scaled by1/sqrt(I0)
Measured Results: LSO Composition
Measured Results: LSO Composition
= Ca-doped
0.1%
0.2%
0.4%0.3%
W. Moses NSS-MIC 2008
• Intrinsic Timing Resolution is 63 ps fwhm• With Detectors, Same Timing as NIM Electronics
• Intrinsic Timing Resolution is 63 ps fwhm• With Detectors, Same Timing as NIM Electronics
Shaper
Shaper
4 ADCs
4 ADCsCFD
Sum
Sum
CFD
CERNTDC
FPGA
Out…
Based on Siemens “Cardinal” electronics.
CFD triggers if any of 4 adjacent modules fire.
CERN HPTDC digitizes arrival time w/ 24 ps LSB.
Pulse height from all 8 modules read out on every trigger.
FPGA uses pulse heights to identify interaction crystal.
FPGA also does calibration, event formatting, etc.
Electronics (W. Moses (IEEE 2008))
Our approach
- Using Silicon Photo ultipliers (compatibility with MRI/MRS)
- develop fast dedicated ASIC timing reolution ~ 100 ps
- using different faster scintillator (LaBr3)
-Starting with:- few channel lab. Electronics -> proving TOF capability- building a prostate probe with SiPm (dedicated readout (Jlab)) phatom tests on MRI scanner
J. Va’Vra IEEE 2008
Test card (48 channels using SPIROC ASIC)
It wil be used to test arrays of SiPm coupled to scintillators (continuous and pixellated (LSO, LYSO, LaBr3)
S. Majewski
Summary and outlook
- prostate cancer detection, diagnosis and staging very difficult
- standard PET systems are not sufficiently sensitive and “precise”
- Compact high resolution high sensititivity PET system is needed (prostate probe + external detector)
- 3D postioning capability- ~ 1 mm spatial resolution, high coincidence detection effciency- ~m12% energy resolution- to get rid of background TOF capability 150-250 ps timing resolution
- better radiotracers + multimodality (TOF – PET & MRI (and MRS) can be the solution
- Modern sensor technology allows to build a PET prostate probe insensitive to magntic fields PET MRI possible
- research program started in Rome (coll. with Majewski) for TOF-PET prototype to be tested in clinical scanner starting with phantoms
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