Because positron emission tomography (PET) provides biochemical information in vivo with the sensitivity at the sub-pico-molar level, pre-clinical research using PET plays an important role in biological and pharmaceutical sciences. However, small animal imaging by PET has been challenging with respect to spatial resolution and sensitivity due to the small volume of the imaging objects. A DOI-encoding technique allows for pre-clinical PET to simultaneously achieve high spatial resolution and high sensitivity. Thus many DOI-encoding methods have been proposed. In this paper we describe why DOI measurements are important, what is required in DOI-encoding designs, and how to extract DOI information in scintillator-based DOI detectors. Recently, there has been a growing interest in DOI measurements for TOF PET detectors to correct time walk as a function of DOI position. Thus, the DOI-encoding method with a high time performance suitable for TOF detectors is now required. The requirements to improve the time resolution in DOI detectors are discussed as well.Keywords Positron emission tomography (PET), Depth of interaction (DOI), Multi-layer detector, Dual-ended readout, Single-ended readout THE IMPORTANCE OF DOI MEASUREMENT Simultaneous improvement in spatial resolution and sensitivityThe PET is an important pre-clinical imaging technique because PET provides biochemical information down to the sub-pico-molar level in vivo [1]. Thus, the development of pre-clinical PET scanners has been actively promoted. The major focus of the development is to obtain a similar quality in small animal images as human images, while the size of the imaging subject decreases and the amount of radiopharmaceutical injected into the small animals is limitedTo obtain a similar level of detail and SNR in mouse images as human images, spatial resolution and sensitivity should be increased. That is why many PET instrument researchers have been attempting for the pre-clinical PET to simultaneously achieve high spatial resolution and high sensitivity. The pre-clinical PET systems therefore have been designed by using very long and narrow crystals with small diameter ring geometry. However, such system structures cause the parallax error to become lager when providing no depth-of-interaction (DOI) information within crystals (general PETs can measure no DOI information), and bring the degradation of the radial resolution in the peripheral field of view (FOV). That is because the reconstruction algorithm, when drawing a line of response (LOR) without DOI information, usually assigns the interaction positions over all depths within a crystal to a single position (i.e. the center position on the front of the interacted crystals).

The most investigated semiconductor photosensor for MRIcompatible PET detectors is the avalanche photodiode (APD). However, the silicon photomultiplier (SiPM), also called the Geiger-mode APD, is gaining attention in the development of the next generation of PET/MRI systems because the SiPM has much better performance than the APD. We have developed an MRI-compatible PET system based on multichannel SiPM arrays to allow simultaneous PET/MRI. Methods: The SiPM PET scanner consists of 12 detector modules with a ring diameter of 13.6 cm and an axial extent of 3.2 cm. In each detector module, 4 multichannel SiPM arrays (with 4 · 4 channels arranged in a 2 · 2 array to yield 8 · 8 channels) were coupled with 20 · 18 Lu 1.9 Gd 0.1 SiO 5 :Ce crystals (each crystal is 1.5 · 1.5 · 7 mm) and mounted on a charge division network for multiplexing 64 signals into 4 position signals. Each detector module was enclosed in a shielding box to reduce interference between the PET and MRI scanners, and the temperature inside the box was monitored for correction of the temperature-dependent gain variation of the SiPM. The PET detector signal was routed to the outside of the MRI room and processed with a field programmable gate array-based data acquisition system. MRI compatibility tests and simultaneous PET/MRI acquisitions were performed inside a 3-T clinical MRI system with 4-cm loop receiver coils that were built into the SiPM PET scanner. Interference between the imaging systems was investigated, and phantom and mouse experiments were performed. Results: No radiofrequency interference on the PET signal or degradation in the energy spectrum and flood map was shown during simultaneous PET/MRI. The quality of the MRI scans acquired with and without the operating PET showed only slight degradation. The results of phantom and mouse experiments confirmed the feasibility of this system for simultaneous PET/MRI. Conclusion: Simultaneous PET/MRI was possible with a multichannel SiPM-based PET scanner, with no radiofrequency interference on PET signals or images and only slight degradation of the MRI scans. A hybrid PET/MRI scanner has many potential advantages, including a reduced radiation dose, better soft-tissue contrast on MRI than CT, an almost unlimited combination of functional and molecular information, and possible motion correction of the PET image using MRI data (1-4). However, simultaneous PET/MRI with a conventional photomultiplier tube (PMT)-based PET camera is technically challenging, because the PMT is highly sensitive to the magnetic field. Almost every property of the PMT PET signal is distorted within the magnetic field. For example, the energy spectrum of the PET detector is quite diminished because of the loss of PMT signal output, and the peak position of the scintillation crystal cannot be distinguished in the flood maps of block detectors (1). Therefore, if relatively long optical fiber bundles are not used, the PMT PET camera should be placed a distance from the MRI machine (5). Consequently, a longer scan time is...

For animal PET systems to achieve high sensitivity without adversely affecting spatial resolution, they must have the ability to measure depth-of-interaction (DOI). In this paper, we propose a novel four-layer PET system, and present the performances of modules built to verify the concept of the system. Each layer in the four-layer PET system has a relative offset of half a crystal pitch from other layers. Performances of the four-layer detector were estimated using a GATE Monte Carlo simulation code. The proposed system consists of six H9500 PMTs, each of which contains 3193 crystals. A sensitivity of 11.8% was obtained at the FOV center position of the proposed system. To verify the concept, we tested a PET module constructed using a H9500 flat panel PMT and LYSO crystals of cross-sectional area 1.5 1.5 mm 2 . The PET module was irradiated with a 1.8 MBq 22 Na radiation source from the front or side of the crystals to obtain flood images of each crystal. Collimation for side irradiation was achieved using a pair of lead blocks of dimension 50 100 200 mm 3 . All crystals in the four layers were clearly identified in flood images, thus verifying the DOI capability of the proposed four-layer PET system. We also investigated the optimal combination of crystal lengths in the four-layer PET system using the GATE Monte Carlo simulation code to generate events from simulated radiation sources, and using the ML-EM algorithm to reconstruct simulated radiation sources. The combination of short crystal lengths near radiation sources and long crystal lengths near the PMT provides better spatial resolution than combinations of same crystal lengths in the four-layer PET system.Index Terms-Depth of interaction (DOI)), four-layer animal PET, GATE Monte Carlo simulation, H9500 photomultiplier tube (PMT).

We propose a depth-of-interaction (DOI)-encoding method to extract continuous DOI information using a single-layer scintillation crystal array with single-ended readout for cost-effective high-resolution positron emission tomography (PET). DOI information is estimated by different light dispersions along the x- and y-directions tailored by the geometric shape of reflectors around the crystals. The detector module comprised a 22 × 22 array of unpolished LGSO crystals (2.0 × 2.0 × 20 mm(3)). A multi-anode photomultiplier tube with 64 anodes measured light dispersion in the crystal array. Gain non-uniformity of each anode was corrected by an analogue gain compensation circuit. DOI information was determined from peaks in the x and y anode-signal distributions normalized by the total energy of the distribution. Average DOI resolution (full width at half maximum, FWHM) over all crystals and depths was estimated to be 4.2 mm. Average energy resolution from the 2 to 18 mm DOI positions was 11.3% ± 0.79%, with 13% difference in photo-peak positions. Average time resolutions (FWHM) were 320-356 ps. Energy, time and DOI resolutions were uniform over all crystal positions except at the array's edge. This DOI-PET detector shows promise for applications that require high resolution and sensitivity at low cost.

Silicon photomultiplier (SiPM; also called a Geiger-mode avalanche photodiode) is a promising semiconductor photosensor in PET and PET/MRI because it is intrinsically MRI-compatible and has internal gain and timing properties comparable to those of a photomultiplier tube. In this study, we have developed a smallanimal PET system using SiPMs and lutetium gadolinium oxyorthosilicate (LGSO) crystals and performed physical evaluation and animal imaging studies to show the feasibility of this system. Methods: The SiPM PET system consists of 8 detectors, each of which comprises 2 · 6 SiPMs and 4 · 13 LGSO crystals. Each crystal has dimensions of 1.5 · 1.5 · 7 mm. The crystal face-toface diameter and axial field of view are 6.0 cm and 6.5 mm, respectively. Bias voltage is applied to each SiPM using a finely controlled voltage supply because the gain of the SiPM strongly depends on the supply voltage. The physical characteristics were studied by measuring energy resolution, sensitivity, and spatial resolution. Various mouse and rat images were obtained to study the feasibility of the SiPM PET system in in vivo animal studies. Reconstructed PET images using a maximum-likelihood expectation maximization algorithm were coregistered with animal CT images. Results: All individual LGSO crystals within the detectors were clearly distinguishable in flood images obtained by irradiating the detector using a 22 Na point source. The energy resolution for individual crystals was 25.8% 6 2.6% on average for 511-keV photopeaks. The spatial resolution measured with the 22 Na point source in a warm background was 1.0 mm (2 mm off-center) and 1.4 mm (16 mm off-center) when the maximum-likelihood expectation maximization algorithm was applied. A myocardial 18 F-FDG study in mice and a skeletal 18 F study in rats demonstrated the fine spatial resolution of the scanner. The feasibility of the SiPM PET system was also confirmed in the tumor images of mice using 18 F-FDG and 68 Ga-RGD and in the brain images of rats using 18 F-FDG. Conclusion: These results indicate that it is possible to develop a PET system using a promising semiconductor photosensor, which yielded reasonable PET performance in phantom and animal studies.

PET detectors with depth-of-interaction (DOI) encoding capability allow high spatial resolution and high sensitivity to be achieved simultaneously. To obtain DOI information from a mono-layer array of scintillation crystals using a single-ended readout, the authors devised a method based on light spreading within a crystal array and performed Monte Carlo simulations with individual scintillation photon tracking to prove the concept. A scintillation crystal array model was constructed using a grid method. Conventional grids are constructed using comb-shaped reflector strips with rectangular teeth to isolate scintillation crystals optically. However, the authors propose the use of triangularly shaped teeth, such that scintillation photons spread only in the x-direction in the upper halves of crystals and in the y-direction in lower halves. DOI positions can be estimated by considering the extent of two-dimensional light dispersion, which can be determined from the multiple anode outputs of a position-sensitive PMT placed under the crystal array. In the main simulation, a crystal block consisting of a 29x29 array of 1.5 mmx1.5 mmx20 mm crystals and a multi-anode PMT with 16x16 pixels were used. The effects of crystal size and non-uniform PMT output gain were also explored by simulation. The DOI resolution estimated for 1.5x1.5x20 mm3 crystals was 2.16 mm on average. Although the flood map was depth dependent, each crystal was well identified at all depths when a corner of the crystal array was irradiated with 511 keV gamma rays (peak-to-valley ratio approximately 9:1). DOI resolution was better than 3 mm up to a crystal length of 28 mm with a 1.5x1.5 mm2 or 2.0x2.0 mm2 crystal surface area. The devised light-sharing method allowed excellent DOI resolutions to be obtained without the use of dual-ended readout or multiple crystal arrays.

Photon detecting Geiger-mode solid-state devices are being actively researched and developed because, unlike photomultiplier tubes (PMT), they can be used in high-magnetic-field and radio-frequency environments, such as in magnetic resonance imaging (MRI) scanners. In addition, some Geiger-mode solid-state devices have higher photon detection efficiencies than PMTs and higher gains than avalanche photo-diodes (APD). We tested Geiger-mode solid-state photomultipliers (SSPM) inside a 3 T MRI to study the possibility of using them in combined PET/MRI scanners. Approximately 16% energy resolutions and 1.3 ns coincidence time resolutions with 22 Na and lutetium yttrium oxyorthosilicate (LYSO) were obtained for full-width at half maximum (FWHM) for T1, T2, and gradient echo T2 MRI pulse sequences with little MR image degradation. The study shows that SSPMs have excellent potential for use in combined PET/MRI scanners.Index Terms-MRI, multimodal imaging, PET, PET/MRI.

Improved spatial resolution without sacrificing sensitivity is one of the most challenging developmental goals for small animal PET scanners. The 3-layer configuration that we propose here utilizes relative offsets of half a crystal pitch in xand y-directions, and pulse shape discrimination to obtain depth of interaction (DOI). Three layers of crystals with a dimension 1.5 1.5 7.0 mm 3 were composed of a L 0 2 GSO (Lu 0 4 Gd 1 6 SiO 4 : Ce) crystal layer and a L 0 9 GSO (Lu 1 8 Gd 0 2 SiO 4 : Ce) crystal layer aligned with each other, and a L 0 9 GSO crystal layer offset at half a crystal pitch in x-and y-directions. The L 0 9 GSO crystal layer was attached to a Hamamatsu H9500 flat-panel PMT. The devised small animal PET scanner has a diameter of 84 mm with one detector ring, and can be upgraded to two detector rings. GEANT4 Monte-Carlo simulation was used to estimate sensitivities of 12% and 20%, respectively, at the center of one and two PMT ring system with an energy window of 350 750 keV. We present flood images with peak-to-valley ratios of about 5-6 obtained using 22 Na and layer identification capability of 99% with pulse shape analysis, and verified the basic concepts of multi-layer small animal PET.Index Terms-Animal PET, depth of interaction (DOI), lutetium gadolinium oxyorthosilicate (LGSO), three-layer crystal.