F. Garibaldi1,, for TOPEM collaboration

1
TOPEM a PET TOF probe, compatible with MRI and
MRS for diagnosis and follow up of prostate cancer
F. Garibaldi1,, for TOPEM collaboration
TOPEM Collaboration A. Gabrielli, F. M. Giorgi -
INFN, University of Bologna - F. Garibaldi, F.
Cusanno, F. Meddi, INFN Roma1 and gruppo
collegato ISS, B. Maraviglia F. Giove, T. Gigli,
University of Roma - R. De Leo, M. Foresta, A.
Ranieri, G. De Robertis, F. Loddo - INFN,
University of Bari - R. Fonte - INFN, Catania -
P. Musico, C. Calvini, P. Ottonello INFN,
University of Genova - L. G. Cosentino, A. D.
Pappalardo, P. Finocchiaro INFN, University of
Catania, LNS N. Clinthorne, S. Huhss -
University of Michigan, S. Majewsky University
of West Virginia
Prostate cancer (PC) is the most common disease
in western countries and a leading cause of
cancer death. The current standard for diagnosing
PC is transrectal ultrasound (TRUS) guided
sextant biopsy. It is the only case of blind
biopsy. Powerfull techniques and instruments such
as CT, MRI, PET/SPECT suffer for limited spatial
resolution, sensitivity and/or specificity.
Dedicated detectors and techniques are needed.
Multimodality imaging can play a significant
role, merging anatomical and functional details
coming from simultaneous PET and MRI (and MRS)
scans. A new research project started with the
goal of designing, building and testing an
endorectal PET-TOF probe compatible with MRI.
SiPM
Dimension, compatibility with magnetic field, and
timing dictate the choice of the photodetector
Silicon Photo Multipliers (SiPM). We started
studying the performances of SiPM for different
companies of different characteristics (microcell
dimension, pixel size etc). Fig show, as
expected, gain reduction with temperature is due
to the variation of breakdown voltage. This put
constraints in the layout with need of cooling,
monitoring the temperature and feedback on the
Voltage. Preminary calculations show that by
water cooling this is possible. Fi show possible
laout of the system.
Drawback of the standard PET

• -- detectors far away from prostate
• - poor spatial resolution (6 12 mm)
• poor photon detection efficiency (lt1)
• activity ouside the organ
• -gt poor contrast resolution

A dedicated external PET detector (W.Moses) will
improve the performances but it is still
limited(y attenuation etc.)
Electronics
Due to geometrical and technical constraints we
will have a detector unit (with ASIC) and a
control unit.The detector will have dual layer of
scintillators and SiPM (for Depth Of Interaction
(DOI) precision measurement). ASIC minimal
implementation will have preamp-discriminators.
In this scenario very high density cabling will
be necessary for off-detector signal processing.
Our goal is to design a final ASIC with all
funcionalities (ADC TDC) with minimal wiring
(serial communication).
Concept of a dedicated prostate imager
An endorectal probe and a PET panel imaging module

1. Imaging (zoom) probe 1.5 mm LYSO arrays
   coupled to a MPPC array

2) Panel PET imager 150 x 200 mm2 LYSO array
cuupled to 4x3 H8500 Hamamatsu for testing
pourposes. Array of SiPM possibly coupled to LYSO
(or Lso array doped with Ca).
TOF measurement
or
We performed preliminary measurement of timing
resolution with a finger LYSO scintillator
obtaining 350 ps FWHM. Substantial improvement
are possible showing that the design goal ( 300
ps) is reachble
Using an external standard PET detector and 1 or
2 panel detectors. High resolution possible if
internal detector has high resolution Attenuation
of activity emitted from prostate lower. (N.
Clinthorne et al.). External high resolution
detectors can augment imaging of superficial
lymph nodes.
Measurements with test detector(s)
Geant4 simulations using Zubal antropomorphic
phantom
-Model 80cm x 15cm x 2cm BGO external
ring -Internal LSO probe, 2 layers of 1mm x 1mm x
3mm crystals in a 9 x 35 array -source in
prostate 20mm from probe face
z
The panel detector an array of 4x3 Hamamatsu
flat panel H8500 PMTs was coupled to the Saint
Gobain array of 2x2x15mm LYSO scintillator
pixels, to form the active FOV imaging surface of
about 15cm x 20cm.
.
x
Probe (1 x 1 x 10 mm2) Lyso. One side readout
with Hamamatsu SiPM
Laminography thirteen planes spaced at 2.5mm in
the z-directionand covering z region between
-15mm to 15mm.Plus direction is away from the
panel imager and towards the probe. All
reconstruction angles, limited only by the
detector sizes and source geometry, were
accepted. Each of the three point sources is best
seen in focus in one of the planes (marked with
red arrows), as expected from the 6 mm vertical
(z) spacing of the sources. The planar spacing
(seen here in the vertical image coordinate) is
5mm.
1.3 mm
0.8 mm
1.2 mm
0.9 mm
Spatial resolution and efficiency increase
dominated by probe resolution and dimension.
Adding one or two panel detectors close to the
patients body would increase the efficiency
helping also detecting the linphonodes
1.1 mm
1.0 mm
Three Na22 point sources spaced vertically at
6mm, and side shifted by 5mm, 45 deg acceptance
angle.
Advantages of TOF
The spatial resolution of the system in the
magnified geometry, similar to the one expected
in imaging of the prostate, is approaching 1.5mm
FWHM (with 1mm LYSO array) in plane when using
simple laminography back projection algorithm.The
vertical (z) resolution is on the order of 5-10mm
FWHM depending on the imaging geometry

• - TOF provides huge performance increase!
• Can localize the source along line of flight.
• In non TOF case the voxels are coupled, the
  statistical noise is increased. TOF information
  reduces the coupling, so the statistical noise.
• If the distance between 2 voxelsgt DXcDT/2 they
  are uncoupled.
• ? increase SNR(NECR)
• - Fast convergence (reduced scan time)

Radiotracers good radiotracers is an issue.
Recently PET-Choline and other tracers gave
better results than FGD. Moreover much better
tracers will be available soon.
With 300 ps FWHM, 4.5 cm (just the dimension of
the prostate). This is challenging but possible
Summary and Outlook A project started, with the
goal of designing, building, testing on phantoms
and possibly on animals (and humans) an
endorectal PET-TOF MRI probe to be used in
coincidence with an external dedicated detector
and/or a standard PET. New, very promising
radiotracers will be tested on animals. Using
SiPM will allow both good TOF resolution (and
consequently great improvement in NECR) and fully
compatibility with MRIMRS. Multimodality and
improvements in spatial resolution and efficiency
will be a crucial step forward in the diagnosis
and follow up of the prostate cancer. TOF
resolution, MRI compatibility, electronics
(mainly the ASIC), miniaturization, algoritmics
and software for full integration of the probe
with panel detector(s) and a standard PET
scanner, are the major challenges. Preliminary
evaluations, simulation and measurements show
that we can build a system fully matching the
design performances.
Multimodality
The advantages of combining PET (functional) with
MRI (morphological and even functional). MRS
offers an adjunct advantage(inversion of
citrate-choline in tumor). This is schallenging
but it has been showed possible (see B. Pichler
et al. Nat. Med.Vol 14, N 4, April 2008)
Reference s1.G. Kellof et al. Challenges in
Clincal Prostate Cancer Role of Imagin. AJR192,
June 2009, pg. 1455. M. Pomper et al. New Agents
and Techniques for Imaging Prostate Cancer. Focus
on molecular Imaging. To be published in JNM. 2.
S.S Huh, N. Clinthorne, W.L. Rogers.
Investigation of an internal PET probe for
prostate cancer Imaging, NIMA 579 (2007 339-343
3. Tay YC et al. Initial study of an asymmetric
PET System dedicated to breast cancer imaging.
IEEE TNS 53 121-126 4. N. Clinthorne et al.
Multi-resolution image reconstruction for high
resolution small anima PET device. IEEE 2003,
Nucl Symp. Conf. Rec. 3 1997-2001 5. J.sS Karp
et al. Benefit of Time of-Flight in PET
Experimental and Clinical Resukts, JNM, February
20, 2008/ nume.107.044834 6. W.W. Moses. Time of
flight revisited, IEEE TNS Vol 50, N. 5 October
2003, 1325 7. M. Conti et al. Comparison of fast
scintillators with TOF PET potential. IEEE TNS
Vol 56., N. 3, June 2009 8.Szcze?sniak et
alTiming Resolution and Decay Time of LSO
Crystals Co-doped with Calcium, TNS