New techniques for early detection of diseases: imaging of small
biological structures with amplifying PET/SPECT probes using SiPm
photodetectors An important component of molecular medicine is
molecular imaging, where the molecular identification of cellular
components, receptors and ligands may allow the detection of early
or hidden lesions allowing a new approach to diagnoses and cure of
diseases. Strong integration is needed between preclinical and
clinical studies. In this framework a key role is played by
techniques employing radionuclides that allow imaging of biological
processes in vivo with very high sensitivity (picomolar level)
providing that a suitable detection system is available. Spin-off
from new progress in technologies developed for and by the nuclear
physics and high energy physics communities (developments in new
scintillators, photodetectors, solid state materials, fast
electronics, fast data acquisition systems, fast computer
algorithms, etc,) play a special, important role in transferring
and implementing the potentially successful instrumentation
technologies to this field. The design of imaging systems
(especially for small animals) is very challenging due to the
concurrent requirements of high spatial resolution and sensitivity.
We discuss the characteristics and performances needed for human
studies and the role of different radionuclide techniques. Few
examples will be given of issues related to human disease diagnosis
(breast and prostate) The emphasis will be on the challenge to
integrate different imaging modalities. M. Baiocchi 1), E. Cisbani
1), N. Clinthorne 13),L. Cosentino 7), E. Cossu 9), F. Cusanno 2),
R. De Leo 4), G. De Vincentis 3), P. Finocchiaro 7), R.Fonte 6) 10)
A. Gabrielli, F. Garibaldi 2), M.L. Magliozzi 1), S. Majewski 10),
G. Marano 1), B. Maraviglia 3), F.Meddi 2), P.Musico 5), M.Musumeci
1),O. Schillaci 9), G. Simonetti 9), M. Moszynski 12), 12),S.
Torrioli 1), B. Tsui 13), L. Vitelli 1) M. Baiocchi 1), E. Cisbani
1), N. Clinthorne 13),L. Cosentino 7), E. Cossu 9), F. Cusanno 2),
R. De Leo 4), G. De Vincentis 3), P. Finocchiaro 7), R.Fonte 6) 10)
A. Gabrielli, F. Garibaldi 2), M.L. Magliozzi 1), S. Majewski 10),
G. Marano 1), B. Maraviglia 3), F.Meddi 2), P.Musico 5), M.Musumeci
1),O. Schillaci 9), G. Simonetti 9), M. Moszynski 12), T.
Szczesniak 12), S. Torrioli 1), B. Tsui 13), L. Vitelli 1) 1) 1))
I.S.S. ROMA (I); 2) INFN ROMA1, Roma(I), 3) University La Sapienza
ROMA 4) INFN Bari, 5) INFN Ge, 6) INFN CT, 7) INFN LNS, 8) INFN Bo;
9) University of Tor Vergata, Roma, 10) West Virginia University;
11) Johns Hopkins University, 12) Szoltan Institute, Varsavia, 13)
Michigan State University Slide 2 Molecular Imaging Modalities CT
Tissue Density, Z A 20-50 m -galactocidase 0.1 mole H / mole 31 P
MRIA H Concentration MF BOLD, DCE 0.1 mm UltrasoundStructure A F
Doppler Optical (Bioluminescence, fluorescence) A Topography M ~10
3 cells quantitative m to mm PET/SPECTRadiotracer M ~1-2 mm PSA
SENSITIVITY 83% SPECIFICITY 17% CT Selective indication : PSA >
10 ng/ml cT3 Gleas on score > 7 diagnosis is made from tissue
obtained on a blind biopsy Need to consider fundamental changes in
the approach to diagnosing prostate cancer In the future,
multimodality imaging approach tailored to each patient PSA DRE
TRUS biopsy Prostate cancer is the most common cancer and the
second leading cause of cancer death. No diagnostic techniques
available. Only PSA, qualitative Slide 12 Limited space for the PET
detector PET detector must not use magnetic materials Could distort
MR image PET detector must not emit in MR frequency Could produce
MR image artifacts MR-compatible PET shielding materials Could
distort MR image MR gradient field-eddy currents Could produce
noise in detector Could heat detector MR RF transmit Could produce
false PET events MR materials Will produce more gamma attenuation
PET/MR Design Challenges -CITRATE that is present in the normal
prostate -CREATINA that may increase in the phlogosis and all the
proliferative processes -COLINE more specific for a neoplastic
transformation PET MRI & MRS Slide 13 Requirements for
radionuclide imaging - radiotracer (high specificity) - high
sensitivity - practical consideration, cost Dedicated high
resolution high sensitivity PET probe for prostate imaging Detector
goals - 3D photon position capability - spatial resolution ~ 1mm -
high coincidence photon efficiency - energy resolution ~ 12% or
better - TOF ~ 300 ps or better drawback of the standard PET -
detectors far away from prostate - poor spatial resolution (6 12
mm) - poor photon detection efficiency ( poor contrast resolution -
relative high cost per study Slide 14 Dedicated PET detector ring
(Moses) Better than standard scannner but still limited. Endorectal
probe: PET coupled to a dedicated detector or to a standard PET
scanner. Spatial resolution and sensitivity dominated by the small
detector close to the prostate huge background from the bladder !!
Could we reduce or eliminate it? Slide 15 Signals from Different
Voxels are Coupled Statistical Noise Does Not Obey Counting
Statistics Signals from Different Voxels are Coupled Statistical
Noise Does Not Obey Counting Statistics If there are N counts in
the image, SNR = TOF provides a huge Performance Increase! SiPm are
needed for TOF ! Slide 16 Timing resolution depends on
-scintillator (kind (n.of photons, decay time, geometry (light
path)) -photodetector (time jitter, capacitance, PDE etc) -coupling
(light collection efficiency) -electronics (in our case has to be
very compact ASIC) - front end - readout architecture Slide 17
Surti, Karp et al. LaBr3 + PMT A big advantage of SiPMs in a fast
timing is a low time jitter, below 100 ps. However, a fast timing
is limited by rather low photon detection efficiency (PDE), not
exceeding 10 20%, depending on the number of pixels. This is of
particular importance in timing with slow scintillators, like LSO,
with the decay time constant of about 40 ns. Thus the expected time
resolution is a direct function of sqr(n.p.e.) (PDE of SiPM). Thus,
the application of SiPMs to TOF PET detectors requires a number of
optimizations related to the size of the device, its PDE, number of
pixels and finally its capacitance. Moszynski Some results with PMT
and SiPm SiPm vs PMT- role of the capacitance Slide 18 Array SiPm
Endorectal (SPECT and) PET [(2.5 x 5 (6) mm2] probe in
multimodality with MRI DOI Majewski -1.2 mm Layout has to be
optimized to avoid undersampling and to optimize DOI (sandwitch)
Slide 19 Detection of vulnerable atherosclrotic plaques in genetic
modified mice Monitoring effects of stem cell therapy SPECT Spatial
resolution 300-800 (tradeoff with efficiency ( ~35 cps/MBq)) Next
measurements: efficiency ~30 times. It can be improved adding
detectors Small animal imaging of cardiovascular diseases To be
integrated in a multimodality platform (optical and MRI). This is
impossible with anger canera based detectors, that have also
limitations in intrinsic spatial resolution It would be impossible
to inject the tracer through the tail vein in infarction mice
models for months. A new deliverey route of delivery(intraperito
neal injection) has been proposed. It works !. 8 detectors can be
installed around the animal: half of them with large FOV imaging
the whole animal to be able to see the homing and fate of the stemm
cells, the other fosucing the hearth to imager the perfusion, in
order to extract information (ejection fractio) on the possible
effects of the therapy Slide 20 Probe close to artery high spatial
resolution & high efficiency transaxial view high 2D resolution
(~2mm) compact PET imaging modules ~1mm 3D resolution compact PET
Probe artery with plaque modules and probe can be moved around the
neck on a gantry Two components: High 3D resolution (~1mm) compact
PET probe with 2x2 FOV High 2D resolution ( = 5x15cm) 1) Imaging
(zoom) probe: double-sided SiPM modules with 1x1x15mm LYSO arrays
2) Modular imager: three or more SiPM based modules with 5cm x 5cm
x 15-20mm thick LYSO crystal plates or arrays Slide 21 T. Zeniya et
al Conceptual design of high resolution SPECT system for Imaging a
selected small ROI of huma brain magnifying probe for brain Slide
22 Summary and conclusions - Molecular imaging is a powerfull tool
for diagnosis and follow up of diseases (multidisciplinarity) -
Radioncuclide technique have an important specific role - Focusing
on small object and imaging at the same time the whole organ
-Multimodality is mandatory in most cases (practical problems, cost
etc) -Dedicated devices are frequently needed (room for research
groups/small companies -Important role of nuclear and high energy
physics concepts and technique -The biological/medical problem has
to be well understood first!! Slide 23 Italian National Health
Institute and INFN Roma1 TESA: E. Cisbani, S. ColilliF. CusannoR.
Fratoni, F. Garibaldi M. Gricia, M. Lucentini, M.L. Magliozzi F.
Santavenere, S. Torrioli Farmaco: G. Marao, M. Musumeci Oncologia:
M. Baiocchi, L. Vitelli Johns Hopkins University, B.Tui, Y Wang
Jefferson Lab;S. Majewski, D. Weisemberger, B. Kross, J. Proffit
Department of Radiology-University of Rome La Sapienza G. De
Vincentis Collaboration University of La Sapienza Roma B.
Maraviglia, F. Giove Michigan State University: N. Clinthorne
Soltan Institute for Nuclear Studies: M. Moszinsky University of
Tor Vergata- Roma: E. Cossu, O Schillaci, G. Simonetti INFN Genova:
P. Musico INFN Bari: R. De Leo, A Ranieri INFN Catania: L.
Cosentino, P. Finoccchiaro INFN LNS:R. Fonte INFN Bologna:A.
Gabrielli INFN Roma1: F. Meddi Slide 24 TOF in PET: Why? 2009 Pisa
Meeting on Instrumentation La Biodola, Italy May 24 - 30, 2009
Thomas C. Meyer/CERN-PH24 From HEP we know: Event patterns
congested by background; Space points help to remove confusion and
improve reconstruction efficiency; Charge division, Stereo view,
delay lines, cathode readout are known methods; In PET similar
problems arise: Count rate contaminated with scattered and random
photons; TOF reduces randoms and increases sensitivity. Data
courtesy of J. S. Karp, IEEE, Trans. Med. Imag. Vol. 10 (D denotes
patient diameter) D = 27cm D = 35cm Lesion Detectability APD SiPM
Scatter Random True
