High-Temporal-Resolution Lung Kinetic Modeling Using Total-Body Dynamic PET with Time-Delay and Dispersion Corrections.

Tracer kinetic modeling in dynamic PET has the potential to improve the diagnosis, prognosis, and research of lung diseases. The advent of total-body PET systems with much greater detection sensitivity enables high-temporal-resolution (HTR) dynamic PET imaging of the lungs. However, existing models may become insufficient for modeling the HTR data. In this paper, we investigate the necessity of additional corrections to the input function for HTR lung kinetic modeling. Methods: Dynamic scans with HTR frames of as short as 1 s were performed on 13 healthy subjects with a bolus injection of about [Formula: see text] of 18F-FDG using the uEXPLORER total-body PET/CT system. Three kinetic models with and without time-delay and dispersion corrections were compared for the quality of lung time-activity curve fitting using the Akaike information criterion. The impact on quantification of 18F-FDG delivery rate [Formula: see text], net influx rate [Formula: see text] and fractional blood volume [Formula: see text] was assessed. Parameter identifiability analysis was also performed to evaluate the reliability of kinetic quantification with respect to noise. Correlation of kinetic parameters with age was investigated. Results: HTR dynamic imaging clearly revealed the rapid change in tracer concentration in the lungs and blood supply (i.e., the right ventricle). The uncorrected input function led to poor time-activity curve fitting and biased quantification in HTR kinetic modeling. The fitting was improved by time-delay and dispersion corrections. The proposed model resulted in an approximately 85% decrease in [Formula: see text], an approximately 75% increase in [Formula: see text], and a more reasonable [Formula: see text] (∼0.14) than the uncorrected model (∼0.04). The identifiability analysis showed that the proposed models had good quantification stability for [Formula: see text], [Formula: see text], and [Formula: see text] The [Formula: see text] estimated by the proposed model with simultaneous time-delay and dispersion corrections correlated inversely with age, as would be expected. Conclusion: Corrections to the input function are important for accurate lung kinetic analysis of HTR dynamic PET data. The modeling of both delay and dispersion can improve model fitting and significantly impact quantification of [Formula: see text], [Formula: see text], and [Formula: see text].

Efficient Delay Correction for Total-Body PET Kinetic Modeling Using Pulse Timing Methods.

Quantitative kinetic modeling requires an input function. A noninvasive image-derived input function (IDIF) can be obtained from dynamic PET images. However, a robust IDIF location (e.g., aorta) may be far from a tissue of interest, particularly in total-body PET, introducing a time delay between the IDIF and the tissue. The standard practice of joint estimation (JE) of delay, along with model fitting, is computationally expensive. To improve the efficiency of delay correction for total-body PET parametric imaging, this study investigated the use of pulse timing methods to estimate and correct for delay. Methods: Simulation studies were performed with a range of delay values, frame lengths, and noise levels to test the tolerance of 2 pulse timing methods-leading edge (LE) and constant fraction discrimination and their thresholds. The methods were then applied to data from 21 subjects (14 healthy volunteers, 7 cancer patients) who underwent a 60-min dynamic total-body 18F-FDG PET acquisition. Region-of-interest kinetic analysis was performed and parametric images were generated to compare LE and JE methods of delay correction, as well as no delay correction. Results: Simulations demonstrated that a 10% LE threshold resulted in biases and SDs at tolerable levels for all noise levels tested, with 2-s frames. Pooled region-of-interest-based results (n = 154) showed strong agreement between LE (10% threshold) and JE methods in estimating delay (Pearson r = 0.96, P < 0.001) and the kinetic parameters vb (r = 0.96, P < 0.001), Ki (r = 1.00, P < 0.001), and K1 (r = 0.97, P < 0.001). When tissues with minimal delay were excluded from pooled analyses, there were reductions in vb (69.4%) and K1 (4.8%) when delay correction was not performed. Similar results were obtained for parametric images; additionally, lesion Ki contrast was improved overall with LE and JE delay correction compared with no delay correction and Patlak analysis. Conclusion: This study demonstrated the importance of delay correction in total-body PET. LE delay correction can be an efficient surrogate for JE, requiring a fraction of the computational time and allowing for rapid delay correction across more than 106 voxels in total-body PET datasets.

Quantitative accuracy in total-body imaging using the uEXPLORER PET/CT scanner.

Absolute quantification of regional tissue concentration of radioactivity in positron emission tomography (PET) is a critical parameter-of-interest across various clinical and research applications and is affected by a complex interplay of factors including scanner calibration, data corrections, and image reconstruction. The emergence of long axial field-of-view (FOV) PET systems widens the dynamic range accessible to PET and creates new opportunities in reducing scan time and radiation dose, delayed or low radioactivity imaging, as well as kinetic modeling of the entire human. However, these imaging regimes impose challenging conditions for accurate quantification due to constraints from image reconstruction, low count conditions, as well as large and rapidly changing radioactivity distribution across a large axial FOV. We comprehensively evaluated the quantitative accuracy of the uEXPLORER total-body scanner in conditions that encompass existing and potential imaging applications (such as dynamic imaging and ultralow-dose imaging) using a set of total-body specific phantom and human measurements. Through these evaluations we demonstrated a relative count rate accuracy of ±3%-4% using the NEMA NU 2-2018 protocol, an axial uniformity spread of ±3% across the central 90% axial FOV, and a 3% activity bias spread from 17 to 474 MBq18F-FDG in a 210 cm long cylindrical phantom. Region-of-interest quantification spread of 1% was found by simultaneously scanning three NEMA NU 2 image quality phantoms, as well as relatively stable volume-of-interest quantification across 0.2%-100% of total counts through re-sampled datasets. In addition, an activity bias spread of -2% to +1% post-bolus injections in human subjects was found. Larger bias changes during the bolus injection phase in humans indicated the difficulty in providing accurate PET data corrections for complex activity distributions across a large dynamic range. Our results overall indicated that the quantitative performance achieved with the uEXPLORER scanner was uniform across the axial FOV and provided the accuracy necessary to support a wide range of imaging applications.

Automatic rat brain image segmentation using triple cascaded convolutional neural networks in a clinical PET/MR.

The purpose of this work was to develop and evaluate a deep learning approach for automatic rat brain image segmentation of magnetic resonance imaging (MRI) images in a clinical PET/MR, providing a useful tool for analyzing studies of the pathology and progression of neurological disease and to validate new radiotracers and therapeutic agents. Rat brain PET/MR images (N = 56) were collected from a clinical PET/MR system using a dedicated small-animal imaging phased array coil. A segmentation method based on a triple cascaded convolutional neural network (CNN) was developed, where, for a rectangular region of interest covering the whole brain, the entire brain volume was outlined using a CNN, then the outlined brain was fed into the cascaded network to segment both the cerebellum and cerebrum, and finally the sub-cortical structures within the cerebrum including hippocampus, thalamus, striatum, lateral ventricles and prefrontal cortex were segmented out using the last cascaded CNN. The dice score coefficient (DSC) between manually drawn labels and predicted labels were used to quantitatively evaluate the segmentation accuracy. The proposed method achieved a mean DSC of 0.965, 0.927, 0.858, 0.594, 0.847, 0.674 and 0.838 for whole brain, cerebellum, hippocampus, lateral ventricles, striatum, prefrontal cortex and thalamus, respectively. Compared with the segmentation results reported in previous publications using atlas-based methods, the proposed method demonstrated improved performance in the whole brain and cerebellum segmentation. In conclusion, the proposed method achieved high accuracy for rat brain segmentation in MRI images from a clinical PET/MR and enabled the possibility of automatic rat brain image processing for small animal neurological research.

Investigating Low-Dose Image Quality in Whole-Body Pediatric 18F-FDG Scans Using Time-of-Flight PET/MRI.

In this study, we investigated the diagnostic performance of whole-body 18F-FDG imaging using a PET/MRI scanner with time-of-flight capability for low-dose clinical imaging of pediatric patients. In addition to clinically acquired image data using a dosing regimen of 3.7 MBq/kg, images from simulated low-dose regimens (1.9-0.41 MBq/kg) were evaluated using several metrics: SUV quantitation, qualitative image quality, and lesion detectability. Methods: Low-dose images were generated by truncating the list-mode PET data to reduce the count statistics. Changes in PET quantitation for low-dose images were assessed using volume-of-interest analysis of healthy tissue and suspected lesions. Three pediatric radiologists reviewed the image volumes without knowing the dose level. Qualitative image quality was assessed on the basis of Likert scoring. Radiologists were also asked to identify suspected lesions within the liver for PET-only and PET/MR images. Lesion detectability was measured using a receiver-operating-characteristic study and quantified using a free-response receiving-operating-characteristic (FROC) methodology to assess changes in performance for low-dose images. Results: Our analysis of volume-of-interest quantitation showed that SUVs remain stable down to ⅓ dose (1.2 MBq/kg). Likert scoring of PET/MR images showed no noticeable trend with dose level; however, scores of PET-only images were lower for low-dose scans, with a 12% reduction for ⅓-dose images compared with full-dose images. There was minimal change in total lesion count for different dose levels; however, all 3 readers had an increase in false-negatives for ⅓-dose images compared with full-dose images. Using the FROC methodology to quantify lesion-detection performance for human observers, no significant differences were observed for the 3 dosing levels when using the averaged reader data (all P values > 0.103). For all readers, the FROC performance was higher for PET/MRI than for PET alone. Conclusion: Reductions to the lowest recommended pediatric dosing regimens are possible when using PET/MRI. The data suggest that the administered dose can be decreased to 2.46 MBq/kg, a 33% reduction in PET activity, with no degradation in image quality, leading to a corresponding reduction in absorbed dose.

Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View.

The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging.

Potential Roles of Total-Body PET/Computed Tomography in Pediatric Imaging.

In the current diagnostic paradigm, the substantial physical sensitivity gain is the main advantage of total-body (TB) PET/computed tomography (CT). Therefore, it is up to the imaging community to tailor protocols that take advantage of this unique innovation as it relates to the needs of the pediatric population. However, the paradigm-shifting promise of TB-PET/CT lies in its capability to perform dynamic, delayed, and low-dose imaging, which have the potential to vastly increase the range of diseases and disorders that can be investigated or managed using molecular imaging.

PennPET Explorer: Design and Preliminary Performance of a Whole-Body Imager.

We report on the development of the PennPET Explorer whole-body imager. Methods: The PennPET Explorer is a multiring system designed with a long axial field of view. The imager is scalable and comprises multiple 22.9-cm-long ring segments, each with 18 detector modules based on a commercial digital silicon photomultiplier. A prototype 3-segment imager has been completed and tested with an active 64-cm axial field of view. Results: The instrument design is described, and its physical performance measurements are presented. These include sensitivity of 55 kcps/MBq, spatial resolution of 4.0 mm, energy resolution of 12%, timing resolution of 256 ps, and a noise-equivalent count rate above 1,000 kcps beyond 30 kBq/mL. After an evaluation of lesion torso phantoms to characterize quantitative accuracy, human studies were performed on healthy volunteers. Conclusion: The physical performance measurements validated the system design and led to high-quality human studies.

The Potential Role of Total Body PET Imaging in Assessment of Atherosclerosis.

Recent advances in molecular imaging and PET instrumentation will be of great value in assessing atherosclerosis plaques and other cardiovascular disorders. Atherosclerosis is systemic and involves critical arteries. Total body PET imaging will allow assessment of disease throughout the body as well as therapeutic monitoring. Because of the high sensitivity of total body PET, delayed imaging can be performed hours after administering tracer compounds, resulting in higher contrast at the disease site. Global assessment of the plaque burden throughout the body will substantially improve our ability to quantify plaque activity in the course of the disease.

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.

Performance Comparison of Different Readouts for Position-Sensitive Solid-State Photomultiplier Arrays.

A thorough comparison of five different readouts for reading out a 2 × 2 array of 5 mm × 5 mm position-sensitive solid-state photomultipliers (PS-SSPM) was undertaken. The five readouts include reading out the 20 signals (16 position and 4 timing) individually, two signal multiplexing readouts, and two position decoding readouts. Flood histogram quality, signal-to-noise ratio (SNR) and energy resolution were compared at different bias voltage (27.0 V to 32.0 V, at 0.5 V intervals) and at a fixed temperature of 0 °C by coupling a 6 × 6 array of 1.3 mm × 1.3 mm × 20 mm polished LSO crystals to the center of the PS-SSPM array. The timing resolution was measured at a bias voltage of 31.0 V (optimal bias voltage in terms of flood histogram quality). The best flood histogram quality value and signal-to-noise were 7.3 ± 1.6 and 33.5 ± 3.1, respectively, and were obtained by shaping and digitizing the 16 position signals individually. The capacitive charge-division readout is the simplest readout among the five evaluated but still resulted in good performance with a flood histogram quality value of 3.3 ± 0.4 and a SNR of 18.3 ± 1.3. The average energy resolution and the average timing resolution were 15.2 ± 1.2 % and 8.4 ± 1.6 ns for individual signal readout and 15.9 ± 1.2 % and 8.8 ± 1.3 ns by using the capacitive charge-division readout method. These studies show that for an ultra-high spatial resolution applications using the 2 × 2 PS-SSPM array, reading out the 20 signals individually is necessary; whilst the capacitive charge-division readout is a cost-effective readout for less demanding applications.

Parallax error in long-axial field-of-view PET scanners-a simulation study.

There is a growing interest in the design and construction of a PET scanner with a very long axial extent. One critical design challenge is the impact of the long axial extent on the scanner spatial resolution properties. In this work, we characterize the effect of parallax error in PET system designs having an axial field-of-view (FOV) of 198 cm (total-body PET scanner) using fully-3D Monte Carlo simulations. Two different scintillation materials were studied: LSO and LaBr3. The crystal size in both cases was 4 × 4 × 20 mm3. Several different depth-of-interaction (DOI) encoding techniques were investigated to characterize the improvement in spatial resolution when using a DOI capable detector. To measure spatial resolution we simulated point sources in a warm background in the center of the imaging FOV, where the effects of axial parallax are largest, and at several positions radially offset from the center. Using a line-of-response based ordered-subset expectation maximization reconstruction algorithm we found that the axial resolution in an LSO scanner degrades from 4.8 mm to 5.7 mm (full width at half max) at the center of the imaging FOV when extending the axial acceptance angle (α) from ±12° (corresponding to an axial FOV of 18 cm) to the maximum of ±67°-a similar result was obtained with LaBr3, in which the axial resolution degraded from 5.3 mm to 6.1 mm. For comparison we also measured the degradation due to radial parallax error in the transverse imaging FOV; the transverse resolution, averaging radial and tangential directions, of an LSO scanner was degraded from 4.9 mm to 7.7 mm, for a measurement at the center of the scanner compared to a measurement with a radial offset of 23 cm. Simulations of a DOI detector design improved the spatial resolution in all dimensions. The axial resolution in the LSO-based scanner, with α = ± 67°, was improved from 5.7 mm to 5.0 mm by incorporating a two-layer DOI detector. These results characterize the maximum axial blurring for a fully open 2 m long PET scanner and demonstrate that large sensitivity gains are possible with a modest reduction in resolution when using current clinical detector technology with no DOI capability.

Characterization of stacked-crystal PET detector designs for measurement of both TOF and DOI.

A PET detector with good timing resolution and two-level depth-of-interaction (DOI) discrimination can be constructed using a single-ended readout of scintillator stacks of Lanthanum Bromide (LaBr3), with various Cerium dopant concentrations, including pure Cerium Bromide (CeBr3). The stacked crystal geometry creates a unique signal shape for interactions occurring in each layer, which can be used to identify the DOI, while retaining the inherently good timing properties of LaBr3 and CeBr3. In this work, single pixel elements are used to optimize the choice of scintillator, coupling of layers, and type of photodetector, evaluating the performance using a fast, single-channel photomultiplier tube (PMT) and a single 4 × 4 mm(2) silicon photomultiplier (SiPM). We also introduce a method to quantify and evaluate the DOI discrimination accuracy. From signal shape measurements using fast waveform sampling, we found that in addition to differences in signal rise times, between crystal layers, there were also differences in the signal fall times. A DOI accuracy of 98% was achieved using our classification method for a stacked crystal pair, consisting of a 15 mm long LaBr3(Ce:20%) crystal on top of a 15 mm long CeBr3 crystal, readout using a PMT. A DOI accuracy of 95% was measured with a stack of two, identical, 12 mm long, CeBr3 crystals. The DOI accuracy of this crystal pair was reduced to 91% when using a SiPM for readout. For the stack of two, 12 mm long, CeBr3 crystals, a coincidence timing resolution (average of timing results from the top and bottom layer) of 199 ps was measured using a PMT, and this was improved to 153 ps when using a SiPM. These results show that with stacked LaBr3/CeBr3 scintillators and fast waveform sampling nearly perfect DOI accuracy can be achieved with excellent timing resolution-timing resolution that is only minimally degraded compared to results from a single CeBr3 crystal of comparable length to the stacked crystals. The interface in the stacked crystal geometry itself plays a major role in creating the differences in signal shape and this can be used to construct stacked DOI detectors using the same scintillator type, thereby simplifying and broadening the application of this technique.

Evaluation of Matrix9 silicon photomultiplier array for small-animal PET.

PURPOSE: The MatrixSL-9-30035-OEM (Matrix9) from SensL is a large-area silicon photomultiplier (SiPM) photodetector module consisting of a 3 × 3 array of 4 × 4 element SiPM arrays (total of 144 SiPM pixels) and incorporates SensL's front-end electronics board and coincidence board. Each SiPM pixel measures 3.16 × 3.16 mm(2) and the total size of the detector head is 47.8 × 46.3 mm(2). Using 8 × 8 polished LSO/LYSO arrays (pitch 1.5 mm) the performance of this detector system (SiPM array and readout electronics) was evaluated with a view for its eventual use in small-animal positron emission tomography (PET). METHODS: Measurements of noise, signal, signal-to-noise ratio, energy resolution, flood histogram quality, timing resolution, and array trigger error were obtained at different bias voltages (28.0-32.5 V in 0.5 V intervals) and at different temperatures (5 °C-25 °C in 5 °C degree steps) to find the optimal operating conditions. RESULTS: The best measured signal-to-noise ratio and flood histogram quality for 511 keV gamma photons were obtained at a bias voltage of 30.0 V and a temperature of 5 °C. The energy resolution and timing resolution under these conditions were 14.2% ± 0.1% and 4.2 ± 0.1 ns, respectively. The flood histograms show that all the crystals in the 1.5 mm pitch LSO array can be clearly identified and that smaller crystal pitches can also be resolved. Flood histogram quality was also calculated using different center of gravity based positioning algorithms. Improved and more robust results were achieved using the local 9 pixels for positioning along with an energy offset calibration. To evaluate the front-end detector readout, and multiplexing efficiency, an array trigger error metric is introduced and measured at different lower energy thresholds. Using a lower energy threshold greater than 150 keV effectively eliminates any mispositioning between SiPM arrays. CONCLUSIONS: In summary, the Matrix9 detector system can resolve high-resolution scintillator arrays common in small-animal PET with adequate energy resolution and timing resolution over a large detector area. The modular design of the Matrix9 detector allows it to be used as a building block for simple, low channel-count, yet high performance, small animal PET or PET/MRI systems.

Timing and Energy Resolution of new near-UV SiPMs coupled to LaBr3:Ce for TOF-PET.

The high light output and fast decay time of LaBr3:Ce scintillation detectors leads to excellent timing performance. To realize the potential of timing resolution with LaBr3:Ce we have investigated the performance with SiPMs, which enable 1-to-1 coupling to individual crystals, and which have been optimized for the near-ultraviolet (NUV) scintillation light emission of LaBr3:Ce. Coincidence timing resolution (CTR) of 100 ps was measured for a 4×4×5 mm3 LaBr3:30%Ce crystal directly coupled to a large-area 4×4 mm2 NUV-SiPM. Results show very little dependence on temperature, in the range of -20° to 20°C, and bias voltage, from 2 V to 5 V over breakdown. Optimal performance was achieved at an over-voltage (OV) range of 3 V - 5 V, at which high gain and high photon detection efficiency are achieved. Though saturation was evident at 511 keV, an energy resolution of 6.8% was measured after correcting for non-linearity. We also measured a CTR of 110 ps for a 4×4×5mm3 LaBr3:5%Ce crystal and 245 ps for a 4×4×30 mm3 LaBr3:5%Ce crystal using the NUV-SIPM. The poorer timing measurement for the 30-mm long crystal is due mainly to a systematic shift in the time pick-off as a function of the depth-of-interaction. The excellent temperature stability, fast rise time, high gain, and low noise of the NUV-SiPM make it a practical and highly appealing photodetector for the readout of a LaBr3:Ce TOF-PET detector.

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.

Timing properties of phosphor-coated polished LSO crystals.

This study investigates a time-of-flight (TOF)-depth-of-interaction (DOI) detector design for positron emission tomography (PET), based on phosphor-coated lutetium oxyorthosilicate (LSO) scintillator crystals coupled to fast single channel photomultiplier tubes. Interaction of the scintillation light with the phosphor coating changes the pulse shape in a depth-dependent manner. 3 × 3 × 10 mm(3) LSO scintillation crystals with polished surfaces were characterized, with and without phosphor coating, to assess DOI capability and timing properties. Two different phosphor coating geometries were studied: coating of the top surface of the crystal, and the top plus half of the crystal sides. There was negligible depth dependency in the decay time when coating only the top surface, however there was a ∼10 ns difference in end-to-end decay time when coating the top plus half of the crystal sides, sufficient to support the use of three DOI bins (3.3 mm DOI bin width). The rise time of the half-coated phosphor crystal was slightly faster at all depths, compared to uncoated crystals, however the signal amplitude was lower. Phosphor coating resulted in depth-dependent photopeak positions with an energy resolution of 13.7%, at a depth of 1 mm, and 15.3%, at a depth of 9 mm, for the half-coated crystal. Uncoated LSO crystals showed no change in photopeak position as a function of depth, with an energy resolution of 10.4%. The head-on coincidence timing resolution (CTR) of two uncoated LSO crystals was 287 ps using constant fraction discrimination for time pick-off. With phosphor coating, the CTR of the top-coated crystal was 314 ps, compared to 384 ps for the half-coated crystal. We demonstrate that the trade-off between timing resolution and DOI resolution can be controlled by the phosphor coating geometry. Here we present preliminary results demonstrating that good DOI resolution can be achieved with only a modest 26% degradation in CTR.

Predicting the timing properties of phosphor-coated scintillators using Monte Carlo light transport simulation.

Current developments in positron emission tomography focus on improving timing performance for scanners with time-of-flight (TOF) capability, and incorporating depth-of-interaction (DOI) information. Recent studies have shown that incorporating DOI correction in TOF detectors can improve timing resolution, and that DOI also becomes more important in long axial field-of-view scanners. We have previously reported the development of DOI-encoding detectors using phosphor-coated scintillation crystals; here we study the timing properties of those crystals to assess the feasibility of providing some level of DOI information without significantly degrading the timing performance. We used Monte Carlo simulations to provide a detailed understanding of light transport in phosphor-coated crystals which cannot be fully characterized experimentally. Our simulations used a custom reflectance model based on 3D crystal surface measurements. Lutetium oxyorthosilicate crystals were simulated with a phosphor coating in contact with the scintillator surfaces and an external diffuse reflector (teflon). Light output, energy resolution, and pulse shape showed excellent agreement with experimental data obtained on 3 × 3 × 10 mm³ crystals coupled to a photomultiplier tube. Scintillator intrinsic timing resolution was simulated with head-on and side-on configurations, confirming the trends observed experimentally. These results indicate that the model may be used to predict timing properties in phosphor-coated crystals and guide the coating for optimal DOI resolution/timing performance trade-off for a given crystal geometry. Simulation data suggested that a time stamp generated from early photoelectrons minimizes degradation of the timing resolution, thus making this method potentially more useful for TOF-DOI detectors than our initial experiments suggested. Finally, this approach could easily be extended to the study of timing properties in other scintillation crystals, with a range of treatments and materials attached to the surface.

A Simple Capacitive Charge-Division Readout for Position-Sensitive Solid-State Photomultiplier Arrays.

A capacitive charge-division readout method for reading out a 2 × 2 array of 5 mm × 5 mm position-sensitive solid-state photomultipliers (PS-SSPM) was designed and evaluated. Using this analog multiplexing method, the 20 signals (16 position, 4 timing) from the PS-SSPM array are reduced to 5 signals (4 position, 1 timing), allowing the PS-SSPM array to be treated as an individual large-area PS-SSPM module. A global positioning approach can now be used, instead of individual positioning for each PS-SSPM in the array, ensuring that the entire light signal is utilized. The signal-to-noise ratio (SNR) and flood histogram quality at different bias voltages (27.5 V to 32.0 V at 0.5 V intervals) and a fixed temperature of 0 °C were evaluated by coupling a 6 × 6 array of 1.3 mm × 1.3 mm × 20 mm polished LSO crystals to the center of the PS-SSPM array. The timing resolution was measured at a fixed bias voltage of 31.0 V and a fixed temperature of 0 °C. All the measurements were evaluated and compared using capacitors with different values and tolerances. Capacitor values ranged from 0.051 nf to 10 nf, and the capacitance tolerance ranged from 1% to 20%. The results show that better performance was achieved using capacitors with smaller values and better capacitance tolerance. Using 0.2 nf capacitors, the SNR, energy resolution and timing resolution were 24.3, 18.2% and 8.8 ns at a bias voltage 31.0 V, respectively. The flood histogram quality was also evaluated by using a 10 × 10 array of 1 mm × 1 mm × 10 mm polished LSO crystals and a 10 × 10 array of 0.7 mm × 0.7 mm × 20 mm unpolished LSO crystals to determine the smallest crystal size resolvable. These studies showed that the high spatial resolution of the PS-SSPM was preserved allowing for 0.7 mm crystals to be identified. These results show that the capacitive charge-division analog signal processing method can significantly reduce the number of electronic channels, from 20 to 5, while retaining the excellent performance of the detector.

Comparison of large-area position-sensitive solid-state photomultipliers for small animal PET.

This paper evaluates the performance of two large-area position-sensitive solid-state photomultipliers (PS-SSPM) for use in small animal PET detector designs. Both PS-SSPM device designs are 1 cm² in area, the first being a 2 × 2 tiled array of 5 mm × 5 mm PS-SSPMs and the second being a 10 mm × 10 mm continuous PS-SSPM. Signal-to-noise measurements were performed to investigate the optimal operating parameters for each device and to compare the performance of the two PS-SSPM designs. A maximum signal-to-noise ratio of 29.3 was measured for the 5 mm PS-SSPM array and 15.1 for the 10 mm PS-SSPM, both measurements were made at 0 °C and at the optimal bias voltage. The best energy resolution measured with an array of 1.3 mm polished LSO crystals was 16% for the 5 mm PS-SSPM array and 18% for the 10 mm PS-SSPM. The timing properties of both devices were similar, with a best timing resolution (in coincidence with an LSO/PMT detector) of 6.8 ns (range 6.8-8.9 ns) and 7.1 ns (range 7.1-9.6 ns) for the 5 mm PS-SSPM and 10 mm PS-SSPM respectively. The 2 × 2 array of 5 mm PS-SSPMs was able to visually resolve the elements in an 0.5 × 0.5 × 20 mm LYSO scintillator array (unpolished, diffuse reflector) with an average peak-to-valley ratio in the flood histograms of ∼11 indicating clear separation of the crystals. Advantages and drawbacks of PET detector designs using PS-SSPM photodetectors are addressed and comparisons to other small-animal PET detector designs using position-sensitive avalanche photodiodes are made.