Evaluation of the MRI compatibility of PET detectors modules for organ-specific inserts in a 3T and 7T MRI scanner.

BACKGROUND: Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners and inserts are valuable tools for accurate diagnosis, treatment planning, and monitoring due to their complementary information. However, the integration of a PET system into an MRI scanner presents technical challenges for a distortion-free operation. PURPOSE: We aim to develop a PET insert dedicated to breast imaging in combination with the 3T PET/MRI scanner Biograph mMR (Siemens Healthineers) as well as a brain PET insert for the 7T MRI scanner MAGNETOM Terra (Siemens Healthineers). For this development, we selected as a basis the C13500 series PET modules (Hamamatsu Photonics K.K.) as they offer an all-in-one solution with a scalable, modular design for compact integration with state-of-the-art performance. The original PET modules were not designed to be operated with an MRI scanner, therefore we implemented several modifications such as signal transmission via plastic optical fiber, radio frequency (RF) shielding of the front-end electronics, and filter for the power supply lines. In this work, we evaluated the mutual MRI compatibility between the modified PET modules and the 3T and 7T MRI scanner. METHODS: We used a proof-of-concept setup with two detectors to comprehensively evaluate a potential distortion of the performance of the modified PET modules whilst exposing them to a variety of MR sequences up to the peak operation conditions of the Biograph mMR. A method using the periodicity of the sequences to identify distortions of the PET events in the phase of RF pulse transmission was introduced. Vice versa, the potential distortion of the Biograph mMR was evaluated by vendor proprietary MRI compatibility test sequences. Afterwards, these studies were extended to the MAGNETOM Terra. RESULTS: No distortions were introduced by gradient field switching (field strength up to 20 mT/m at a slew rate of 66.0 T/ms-1 ). However, RF pulse transmission induced a reduction of the single event rate from 33.0 kcounts/s to 32.0 kcounts/s and a degradation of the coincidence resolution time from 251 to 299 ps. Further, the proposed method revealed artifacts in the energy and timing histograms. Finally, by using the front-end filters it was possible to prevent any RF pulse induced distortion of event rate, energy, or time stamps even for a 700° flip angle (45.5 µT) sequence. The evaluations to assess potential distortions of the MRI scanner showed that carefully designed RF shielding boxes for the PET modules were required to prevent distortion of the RF spectra. The increase in B0 field inhomogeneity of 0.254 ppm and local changes of the B1 field of 12.5% introduced by the PET modules did not qualitatively affect the MR imaging with a spin echo and MPRAGE sequence for the Biograph mMR and the MAGNETOM Terra, respectively. CONCLUSION: Our study demonstrates the feasibility of using a modified version of the PET modules in combination with 3T and 7T MRI scanners. Building upon the encouraging MRI compatibility results from our proof-of-concept detectors, we will proceed to develop PET inserts for breast and brain imaging using these modules.

Author Correction: Hybrid PET/MRI enables high-spatial resolution, quantitative imaging of amyloid plaques in an Alzheimer's disease mouse model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Hybrid PET/MRI enables high-spatial resolution, quantitative imaging of amyloid plaques in an Alzheimer's disease mouse model.

The emergence of PET probes for amyloid plaques and neurofibrillary tangles, hallmarks of Alzheimer disease (AD), enables monitoring of pathology in AD mouse models. However, small-animal PET imaging is limited by coarse spatial resolution. We have installed a custom-fabricated PET insert into our small-animal MRI instrument and used PET/MRI hybrid imaging to define regions of amyloid vulnerability in 5xFAD mice. We compared fluorine-18 [18F]-Florbetapir uptake in the 5xFAD brain by dedicated small-animal PET/MRI and PET/CT to validate the quantitative measurement of PET/MRI. Next, we used PET/MRI to define uptake in six brain regions. As expected, uptake was comparable to wild-type in the cerebellum and elevated in the cortex and hippocampus, regions implicated in AD. Interestingly, uptake was highest in the thalamus, a region often overlooked in AD studies. Development of small-animal PET/MRI enables tracking of brain region-specific pathology in mouse models, which may prove invaluable to understanding AD progression and therapeutic development.

A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by 18F-positron emitting tomography and fluorescence.

PURPOSE: Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS). METHODS: We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [18F]-IR783-AMBF3. [18F]-IR783-AMBF3 was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes. RESULTS: IR783-AMBF3 was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF3 (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF3 was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF3 was safe under the tested dosage both in vitro and in vivo. CONCLUSION: The superior imaging properties of IR783-AMBF3 could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS.

Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER.

The world's first 194-cm-long total-body PET/CT scanner (uEXPLORER) has been built by the EXPLORER Consortium to offer a transformative platform for human molecular imaging in clinical research and health care. Its total-body coverage and ultra-high sensitivity provide opportunities for more accurate tracer kinetic analysis in studies of physiology, biochemistry, and pharmacology. The objective of this study was to demonstrate the capability of total-body parametric imaging and to quantify the improvement in image quality and kinetic parameter estimation by direct and kernel reconstruction of the uEXPLORER data. Methods: We developed quantitative parametric image reconstruction methods for kinetic analysis and used them to analyze the first human dynamic total-body PET study. A healthy female subject was recruited, and a 1-h dynamic scan was acquired during and after an intravenous injection of 256 MBq of 18F-FDG. Dynamic data were reconstructed using a 3-dimensional time-of-flight list-mode ordered-subsets expectation maximization (OSEM) algorithm and a kernel-based algorithm with all quantitative corrections implemented in the forward model. The Patlak graphical model was used to analyze the 18F-FDG kinetics in the whole body. The input function was extracted from a region over the descending aorta. For comparison, indirect Patlak analysis from reconstructed frames and direct reconstruction of parametric images from the list-mode data were obtained for the last 30 min of data. Results: Images reconstructed by OSEM showed good quality with low noise, even for the 1-s frames. The image quality was further improved using the kernel method. Total-body Patlak parametric images were obtained using either indirect estimation or direct reconstruction. The direct reconstruction method improved the parametric image quality, having a better contrast-versus-noise tradeoff than the indirect method, with a 2- to 3-fold variance reduction. The kernel-based indirect Patlak method offered image quality similar to the direct Patlak method, with less computation time and faster convergence. Conclusion: This study demonstrated the capability of total-body parametric imaging using the uEXPLORER. Furthermore, the results showed the benefits of kernel-regularized reconstruction and direct parametric reconstruction. Both can achieve superior image quality for tracer kinetic studies compared with the conventional indirect OSEM for total-body imaging.

Compton PET: a layered structure PET detector with high performance.

In most high-resolution PET detector designs, there is an inherent trade-off between spatial resolution and detector efficiency. We have developed and tested a new geometry for the detector module which avoids this trade-off. The module uses a layered structure, in which four crystal slabs are stacked in the depth direction and optically separated by enhanced specular reflector (ESR) film. The scintillation light within each layer is measured by 16 SiPMs located on the four sides of the crystal. Analog signals from all SiPMs (4 × 16) on the four sides of the crystal are digitized individually using a 64-channel TOFPET-2 module. The four-sided readout method reduces the problem of light trapping resulting from total internal reflection when reading out the end(s) of traditional scintillation crystal arrays, thus increasing the light collection efficiency. In this work, we demonstrate the readout of a complete layered detector with 4 layers. The high light collection efficiency results in a FWHM energy resolution of 10.3%, and a FWHM timing resolution of 348 ps. The distribution of scintillation light detected by the SiPMs was used to decode the interaction position of each gamma ray using a trained neural network. A FWHM spatial resolution of 1.1 ± 0.1 mm was achieved. This design allows the detection efficiency of the module to be increased by adding additional crystal slabs along the depth direction. Since the position, energy, and timing are measured for each layer independently, increasing the system sensitivity by adding more layers will not affect the spatial/energy/timing resolution. Furthermore, the layered structure allows partial recovery of position information for events that undergo Compton scatter within the detector.

Mini EXPLORER II: a prototype high-sensitivity PET/CT scanner for companion animal whole body and human brain scanning.

As part of the EXPLORER total-body positron emission tomography (PET) project, we have designed and built a high-resolution, high-sensitivity PET/CT scanner, which is expected to have excellent performance for companion animal whole body and human brain imaging. The PET component has a ring diameter of 52 cm and an axial field of view of 48.3 cm. The detector modules are composed of arrays of lutetium (yttrium) oxyorthosilicate (LYSO) crystals of dimensions 2.76 × 2.76 × 18.1 mm3 coupled to silicon photomultipliers (SiPMs) for read-out. The CT component is a 24 detector row CT scanner with a 50 kW x-ray tube. PET system time-of-flight resolution was measured to be 409 ± 39 ps and average system energy resolution was 11.7% ± 1.5% at 511 keV. The NEMA NU2-2012 system sensitivity was found to be 52-54 kcps MBq-1. Spatial resolution was 2.6 mm at 10 mm from the center of the FOV and 2.0 mm rods were clearly resolved on a mini-Derenzo phantom. Peak noise-equivalent count (NEC) rate, using the NEMA NU 2-2012 phantom, was measured to be 314 kcps at 9.2 kBq cc-1. The CT scanner passed the technical components of the American College of Radiology (ACR) accreditation tests. We have also performed scans of a Hoffman brain phantom and we show images from the first canine patient imaged on this device.

Compton PET: A Simulation Study for a PET Module with Novel Geometry and Machine Learning for Position Decoding.

This paper describes a simulation study of a positron emission tomography (PET) detector module that can reconstruct the kinematics of Compton scattering within the scintillator. We used a layer structure, with which we could recover the positions and energies for the multiple interactions of a gamma ray in the different layers. Using the Compton scattering formalism, the sequence of interactions can be estimated. The true first interaction position extracted in the Compton scattering will help minimize the degradation of the reconstructed image resolution caused by intercrystal scatter events. Because of the layer structure, this module also has readily available user-defined resolution for the depth of interaction. The semi-monolithic crystals enable high light collection efficiency and an energy resolution of ~10% has been achieved in the simulation. We used machine learning to decode the gamma ray interaction locations, achieving an average spatial resolution of 0.40 mm. Our proposed detector design provides a pathway to increase the sensitivity of a system without affecting other key performance features.

Optimization of a depth of interaction encoding PET block detector for a PET/MRI insert.

Preclinical positron emission tomography, combined with magnetic resonance imaging (PET/MRI), is increasingly used as a tool to simultaneously characterize functional processes in vivo. Many emerging preclinical applications, however, are limited by PET detection sensitivity, especially when generating short imaging frames for quantitative studies. One such application is dynamic multifunctional imaging, which probes multiple aspects of a biological process, using relationships between the datasets to quantify interactions. These studies have limited accuracy due to the relatively low sensitivity of modern preclinical PET/MRI systems. The goal of this project is to develop a preclinical PET/MRI insert with detection sensitivity above 15% (250-750 keV) to improve quantitation in dynamic PET imaging. To achieve this sensitivity, we have developed a detector module incorporating a 2 cm thick crystal block, which will be arranged into a system with 8 cm axial FOV, targeting mice and rats. To maintain homogenous spatial resolution, the detector will incorporate dual-ended depth-of-interaction (DOI) encoding with silicon photomultiplier (SiPM) based photodetector arrays. The specific aim of this work is to identify a detector configuration with adequate performance for the proposed system. We have optimized the SiPM array geometry and tested two crystal array materials with pitch ranging from 0.8 to 1.2 mm and various surface treatments and reflectors. From these configurations, we have identified the best balance between crystal separation, energy resolution, and DOI resolution. The final detector module uses two rectangular SiPM arrays with 5 × 6 and 5 × 4 elements. The photodetector arrays are coupled to a 19 × 19 array of 1 mm pitch LYSO crystals with polished surfaces and a diffuse reflector. The prototype design has 14.3% ± 2.9% energy resolution, 3.57 ± 0.88 mm DOI resolution, and resolves all elements in the crystal array, giving it sufficient performance to serve as the basis for the proposed high sensitivity PET/MRI insert.

Performance assessment of a software-based coincidence processor for the EXPLORER total-body PET scanner.

Coincidence processing in positron emission tomography (PET) is typically done during acquisition of the data. However, on the EXPLORER total-body PET scanner we plan, in addition, to store unpaired single events (i.e. singles) for post-acquisition coincidence processing. A software-based coincidence processor was developed for EXPLORER and its performance was assessed. Our results showed that the performance of the coincidence processor could be significantly impacted by the type of data storage (Peripheral Component Interconnect Express (PCIe)-attached solid state drive (SSD) versus RAID 6 hard disk drives (HDDs)) especially when multiple data files were processed in parallel. We showed that a 48-thread computer node with dual Intel Xeon E5-2650 v4 central processing units (CPUs) and a PCIe SSD was sufficient to process approximately 120 M singles s-1 at an incoming singles rate of approximately 150 Mcps. With two computer nodes, near real-time coincidence processing became possible at this incoming singles rate.

Development and Evaluation of mini-EXPLORER: A Long Axial Field-of-View PET Scanner for Nonhuman Primate Imaging.

We describe a long axial field-of-view (FOV) PET scanner for high-sensitivity and total-body imaging of nonhuman primates and present the physical performance and first phantom and animal imaging results. Methods: The mini-EXPLORER PET scanner was built using the components of a clinical scanner reconfigured with a detector ring diameter of 43.5 cm and an axial length of 45.7 cm. National Electrical Manufacturers Association (NEMA) NU-2 and NU-4 phantoms were used to measure sensitivity and count rate performance. Reconstructed spatial resolution was investigated by imaging a radially stepped point source and a Derenzo phantom. The effect of the wide acceptance angle was investigated by comparing performance with maximum acceptance angles of 14°-46°. Lastly, an initial assessment of the in vivo performance of the mini-EXPLORER was undertaken with a dynamic 18F-FDG nonhuman primate (rhesus monkey) imaging study. Results: The NU-2 total sensitivity was 5.0%, and the peak noise-equivalent count rate measured with the NU-4 monkey scatter phantom was 1,741 kcps, both obtained using the maximum acceptance angle (46°). The NU-4 scatter fraction was 16.5%, less than 1% higher than with a 14° acceptance angle. The reconstructed spatial resolution was approximately 3.0 mm at the center of the FOV, with a minor loss in axial spatial resolution (0.5 mm) when the acceptance angle increased from 14° to 46°. The rhesus monkey 18F-FDG study demonstrated the benefit of the high sensitivity of the mini-EXPLORER, including fast imaging (1-s early frames), excellent image quality (30-s and 5-min frames), and late-time-point imaging (18 h after injection), all obtained at a single bed position that captured the major organs of the rhesus monkey. Conclusion: This study demonstrated the physical performance and imaging capabilities of a long axial FOV PET scanner designed for high-sensitivity imaging of nonhuman primates. Further, the results of this study suggest that a wide acceptance angle can be used with a long axial FOV scanner to maximize sensitivity while introducing only minor trade-offs such as a small increase in scatter fraction and slightly degraded axial spatial resolution.

Development of an Ultra High Resolution PET Scanner for Imaging Rodent Paws: PawPET.

A positron emission tomography (PET) scanner with submillimeter spatial resolution, capable of in vivo imaging of murine extremities was built based on two dual ended readout, hybrid depth of interaction (DOI) PET detectors. Each was composed of a 36 × 36 array of 0.43 mm × 0.43 mm × 8 mm unpolished lutetium oxyorthosilicate crystals separated by a 50 µm white diffuse reflector. The array was coupled to a position-sensing photomultiplier tube at one end and to an avalanche photodiode at the other end. The detector characterization included crystal identification accuracy, DOI, energy, and timing resolution measurements. The scanner was characterized in terms of its spatial resolution and its sensitivity and mouse images were acquired of a mouse paw injected with 18-F-NaF. Out of the 36 × 36 crystals only 33 × 33 crystals were identified. The coincidence timing, DOI, and energy resolution of the scanner was measured to be 2.8 ns, 1.4 mm, and 27%, respectively. The scanner's spatial resolution was measured with a line source and determined from an ordered subsets expectation maximization reconstruction to be 0.56 mm. The sensitivity of the scanner was measured to be 0.6% at the center of the field of view.

A Time-Walk Correction Method for PET Detectors Based on Leading Edge Discriminators.

The leading edge timing pick-off technique is the simplest timing extraction method for PET detectors. Due to the inherent time-walk of the leading edge technique, corrections should be made to improve timing resolution, especially for time-of-flight PET. Time-walk correction can be done by utilizing the relationship between the threshold crossing time and the event energy on an event by event basis. In this paper, a time-walk correction method is proposed and evaluated using timing information from two identical detectors both using leading edge discriminators. This differs from other techniques that use an external dedicated reference detector, such as a fast PMT-based detector using constant fraction techniques to pick-off timing information. In our proposed method, one detector was used as reference detector to correct the time-walk of the other detector. Time-walk in the reference detector was minimized by using events within a small energy window (508.5 - 513.5 keV). To validate this method, a coincidence detector pair was assembled using two SensL MicroFB SiPMs and two 2.5 mm × 2.5 mm × 20 mm polished LYSO crystals. Coincidence timing resolutions using different time pick-off techniques were obtained at a bias voltage of 27.5 V and a fixed temperature of 20 °C. The coincidence timing resolution without time-walk correction were 389.0 ± 12.0 ps (425 -650 keV energy window) and 670.2 ± 16.2 ps (250-750 keV energy window). The timing resolution with time-walk correction improved to 367.3 ± 0.5 ps (425 - 650 keV) and 413.7 ± 0.9 ps (250 - 750 keV). For comparison, timing resolutions were 442.8 ± 12.8 ps (425 - 650 keV) and 476.0 ± 13.0 ps (250 - 750 keV) using constant fraction techniques, and 367.3 ± 0.4 ps (425 - 650 keV) and 413.4 ± 0.9 ps (250 - 750 keV) using a reference detector based on the constant fraction technique. These results show that the proposed leading edge based time-walk correction method works well. Timing resolution obtained using this method was equivalent to that obtained using a reference detector and was better than that obtained using constant fraction discriminators.

Sinogram Blurring Matrix Estimation From Point Sources Measurements With Rank-One Approximation for Fully 3-D PET.

An accurate system matrix is essential in positron emission tomography (PET) for reconstructing high quality images. To reduce storage size and image reconstruction time, we factor the system matrix into a product of a geometry projection matrix and a sinogram blurring matrix. The geometric projection matrix is computed analytically and the sinogram blurring matrix is estimated from point source measurements. Previously, we have estimated a 2-D blurring matrix for a preclinical PET scanner. The 2-D blurring matrix only considers blurring effects within a transaxial sinogram and does not compensate for inter-sinogram blurring effects. For PET scanners with a long axial field of view, inter-sinogram blurring can be a major problem influencing the image quality in the axial direction. Hence, the estimation of a 4-D blurring matrix is desirable to further improve the image quality. The 4-D blurring matrix estimation is an ill-conditioned problem due to the large number of unknowns. Here, we propose a rank-one approximation for each blurring kernel image formed by a row vector of the sinogram blurring matrix to improve the stability of the 4-D blurring matrix estimation. The proposed method is applied to the simulated data as well as the real data obtained from an Inveon microPET scanner. The results show that the newly estimated 4-D blurring matrix can improve the image quality over those obtained with a 2-D blurring matrix and requires less point source scans to achieve similar image quality compared with an unconstrained 4-D blurring matrix estimation.

Open-field mouse brain PET: design optimisation and detector characterisation.

'Open-field' PET, in which an animal is free to move within an enclosed space during imaging, is a very promising advance for neuroscientific research. It provides a key advantage over conventional imaging under anesthesia by enabling functional changes in the brain to be correlated with an animal's behavioural response to environmental or pharmacologic stimuli. Previously we have demonstrated the feasibility of open-field imaging of rats using motion compensation techniques applied to a commercially available PET scanner. However, this approach of 'retro-fitting' motion compensation techniques to an existing system is limited by the inherent geometric and performance constraints of the system. The goal of this project is to develop a purpose-built PET scanner with geometry, motion tracking and imaging performance tailored and optimised for open-field imaging of the mouse brain. The design concept is a rail-based sliding tomograph which moves according to the animal's motion. Our specific aim in this work was to evaluate candidate scanner designs and characterise the performance of a depth-of-interaction detector module for the open-field system. We performed Monte Carlo simulations to estimate and compare the sensitivity and spatial resolution performance of four scanner geometries: a ring, parallel plate, and two box variants. Each system was based on a detector block consisting of a 23 × 23 array of 0.785 × 0.785 × 20 mm3 LSO crystals (overall dim. 19.6 × 19.6 × 20 mm). We found that a DoI resolution capability of 3 mm was necessary to achieve approximately uniform sub-millimetre spatial resolution throughout the FoV for all scanners except the parallel-plate geometry. With this DoI performance, the sensitivity advantage afforded by the box geometry with overlapping panels (16% peak absolute sensitivity, a 36% improvement over the ring design) suggests this unconventional design is best suited for imaging the mouse brain. We also built and characterised the block detector modelled in the simulations, including a dual-ended readout based on 6 × 6 arrays of through-silicon-via silicon photomultipliers (active area 84%) for DoI estimation. Identification of individual crystals in the flood map was excellent, energy resolution varied from 12.4% ± 0.6% near the centre to 24.4% ± 3.4% at the ends of the crystal, and the average DoI resolution was 2.8 mm ± 0.35 mm near the central depth (10 mm) and 3.5 mm ± 1.0 mm near the ends. Timing resolution was 1.4 ± 0.14 ns. Therefore, the DoI detector module meets the target specifications for the application and will be used as the basis for a prototype open-field mouse PET scanner.

Characterization of Large-Area SiPM Array for PET Applications.

The performance of an 8 × 8 array of 6.0 × 6.0 mm2 (active area) SiPMs was evaluated for PET applications using crystal arrays with different pitch sizes (3.4 mm, 1.5 mm, 1.35 mm and 1.2 mm) and custom designed five-channel front-end readout electronics (four channels for position information and one channel for timing information). The total area of this SiPM array is 57.4 × 57.4 mm2, and the pitch size is 7.2 mm. It was fabricated using enhanced blue sensitivity SiPMs (MicroFB-60035-SMT) with peak spectral sensitivity at 420 nm. The performance of the SiPM array was characterized by measuring flood histogram decoding quality, energy resolution, timing resolution and saturation at several bias voltages (from 25.0 V to 30.0 V in 0.5 V intervals) and two different temperatures (5 °C and 20 °C). Results show that the best flood histogram was obtained at a bias voltage of 28.0 V and 5 °C and an array of polished LSO crystals with a pitch as small as 1.2 mm can be resolved. No saturation was observed up to a bias voltage of 29.5 V during the experiments, due to adequate light sharing between SiPMs. Energy resolution and timing resolution at 5 °C ranged from 12.7 ± 0.8% to 14.6 ± 1.4 % and 1.58 ± 0.13 ns to 2.50 ± 0.44 ns, for crystal array pitch sizes of 3.4 mm and 1.2 mm respectively. Superior flood histogram quality, energy resolution and timing resolution were obtained with larger crystal array pitch sizes and at lower temperature. Based on our findings, we conclude that this large-area SiPM array can serve as a suitable photodetector for high-resolution small-animal PET or dedicated human brain PET scanners.

A Prototype High-Resolution Small-Animal PET Scanner Dedicated to Mouse Brain Imaging.

UNLABELLED: We developed a prototype small-animal PET scanner based on depth-encoding detectors using dual-ended readout of small scintillator elements to produce high and uniform spatial resolution suitable for imaging the mouse brain. METHODS: The scanner consists of 16 tapered dual-ended-readout detectors arranged in a 61-mm-diameter ring. The axial field of view (FOV) is 7 mm, and the transaxial FOV is 30 mm. The scintillator arrays consist of 14 × 14 lutetium oxyorthosilicate elements, with a crystal size of 0.43 × 0.43 mm at the front end and 0.80 × 0.43 mm at the back end, and the crystal elements are 13 mm long. The arrays are read out by 8 × 8 mm and 13 × 8 mm position-sensitive avalanche photodiodes (PSAPDs) placed at opposite ends of the array. Standard nuclear-instrumentation-module electronics and a custom-designed multiplexer are used for signal processing. RESULTS: The detector performance was measured, and all but the crystals at the very edge could be clearly resolved. The average intrinsic spatial resolution in the axial direction was 0.61 mm. A depth-of-interaction resolution of 1.7 mm was achieved. The sensitivity of the scanner at the center of the FOV was 1.02% for a lower energy threshold of 150 keV and 0.68% for a lower energy threshold of 250 keV. The spatial resolution within a FOV that can accommodate the entire mouse brain was approximately 0.6 mm using a 3-dimensional maximum-likelihood expectation maximization reconstruction. Images of a hot-rod microphantom showed that rods with a diameter of as low as 0.5 mm could be resolved. The first in vivo studies were performed using (18)F-fluoride and confirmed that a 0.6-mm resolution can be achieved in the mouse head in vivo. Brain imaging studies with (18)F-FDG were also performed. CONCLUSION: We developed a prototype PET scanner that can achieve a spatial resolution approaching the physical limits of a small-bore PET scanner set by positron range and detector interaction. We plan to add more detector rings to extend the axial FOV of the scanner and increase sensitivity.

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia.

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-ᴅ-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

Un-collimated single-photon imaging system for high-sensitivity small animal and plant imaging.

In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. However, such high-resolution systems have relatively poor sensitivity (typically 0.01-0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatial resolution, linearity, detection limits, and uniformity. With (99m)Tc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system's linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using (99m)Tc MAG-3 and a thyroid scan with (123)I) and one plant study (a (99m)TcO4(-) xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.

A Study of Position-Sensitive Solid-State Photomultiplier Signal Properties.

We present an analysis of the signal properties of a position-sensitive solid-state photomultiplier (PS-SSPM) that has an integrated resistive network for position sensing. Attractive features of PS-SSPMs are their large area and ability to resolve small scintillator crystals. However, the large area leads to a high detector capacitance, and in order to achieve high spatial resolution a large network resistor value is required. These inevitably create a low-pass filter that drastically slows what would be a fast micro-cell discharge pulse. Significant changes in the signal shape of the PS-SSPM cathode output as a function of position are observed, which result in a position-dependent time delay when using traditional time pick-off methods such as leading edge discrimination and constant fraction discrimination. The timing resolution and time delay, as a function of position, were characterized for two different PS-SSPM designs, a continuous 10 mm × 10 mm PS-SSPM and a tiled 2 × 2 array of 5 mm × 5 mm PS-SSPMs. After time delay correction, the block timing resolution, measured with a 6 × 6 array of 1.3 × 1.3 × 20 mm3 LSO crystals, was 8.6 ns and 8.5 ns, with the 10 mm PS-SSPM and 5 mm PS-SSPM respectively. The effect of crystal size on timing resolution was also studied, and contrary to expectation, a small improvement was measured when reducing the crystal size from 1.3 mm to 0.5 mm. Digital timing methods were studied and showed great promise for allowing accurate timing by implementation of a leading edge time pick-off. Position-dependent changes in signal shape on the anode side also are present, which complicates peak height data acquisition methods used for positioning. We studied the effect of trigger position on signal amplitude, flood histogram quality, and depth-of-interaction resolution in a dual-ended readout detector configuration. We conclude that detector timing and positioning can be significantly improved by implementation of digital timing methods and by accounting for changes in the shape of the signals from PS-SSPMs.