F. Garibaldi1,, F. Cusanno1), S. Majewski3), N. Clinthorne, P. Musico4),………………………….

TOPEM: a PET TOF probe, compatible with MRI and MRS for diagnosis and follow up of prostate

cancer

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. 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 form 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.

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An endorectal probe and a PET panel imaging moduleAn endorectal probe and a PET panel imaging module

1) Imaging (“zoom”) probe: 1.5 mm LYSO arrays coupled to a MPPC array

PET Ring

Prostate

Internal Detector

PET Ring

Prostate

Internal Detector

PET Ring

Prostate

Internal Detector

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.

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

A dedicated external PET detector (W.Moses) will improve the performances but it is still limited(y attenuation etc.)

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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

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BGO+LSO Probe 1

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BGO+LSO Probe 2

BGO Only Probe 2

Spatial resolution and efficiency increase dominated by probe resolution and dimension. Adding one or two panel detectorscolse to the patoent’s body would increase the efficiency helping also detecting the linphonodes

1) I.NFN ROMA (I); 3) West Virginia University; 4) I.N.F.N. Genova – via Dodecaneso, 33 – 16146 – GENOVA (I); 5) Johns Hopkins University,………………………………

Concept of a dedicated prostate imager

Advantages of TOF

SiPM

Electronics

- 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. TOFTOF information reduces the couplingreduces the coupling, so the statistical noisestatistical noise. - If the distance between 2 voxels> DX=cDT/2 they are uncoupled.

increase SNR(NECRincrease SNR(NECR))- Fast convergence (reduced scan time)

With 300 ps FWHM, 4.5 cm (just the dimension of the

prostate). This is challenging but

possible

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. Thisput constraints in the layout with need of cooling, moniitoring the temperature and feedback on the Voltage. Preminary calculations show that by water cooling this is possible. Fig…b show possible laout of the system.

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 will be to design a final ASIC with all funcionalities (ADC + TDC) with minimal wiring (serial communication).

TOF measurement

We performed preliminary measurement of timing resolution with a finger LYSO scintillator obtaining ~ 300 ps FWHM. Substantial improvement are possible showing that the design goal (≤ 300 ps) is reachble

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).

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Multimodality

The advantages of combining PET (functional) with MRI (morphological and even functional). MRS offers an adjunct advantage(inversion of citrate-choline in tumor)Thi is schallenging but it has been showed possible (see B. Pichler et al. “Simultaneous PET-MRI, a new approach “ Nature Medicine Vol 14, N 4, April 2008)

Measurements with test detectir(s)

Probe: (1 x 1 x 10 mm2) Lyso. One side readout with Hamamatsu SiPM

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.

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Three Na22 point sources spaced vertically at 6mm, and side shifted by 5mm, 45 deg acceptance angle.

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.

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