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.

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.

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.

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.

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.

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.

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 v_b (r = 0.96, P < 0.001), K_i (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 v_b (69.4%) and K₁ (4.8%) when delay correction was not performed. Similar results were obtained for parametric images; additionally, lesion K_i 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.

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.

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.

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.