Performance Characteristics of the NeuroEXPLORER, a Next-Generation Human Brain PET/CT Imager.

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial 18F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain 18F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications.

Design, development and evaluation of a resistor-based multiplexing circuit for a 20×20 SiPM array.

One technical challenge in developing a large-size scintillator detector with multiple Silicon Photomultiplier (SiPM) arrays is to read out a large number of detector output channels. To achieve this, different signal multiplexing circuits have been studied and applied with different performances and cost-effective tradeoffs. Resistor-based multiplexing circuits exhibit simplicity and signal integrity, but also present the disadvantage of timing shift among different channels. In this study, a resistor-based multiplexing circuit for a large-sized SiPM array readout was developed and evaluated by simulation and experimental studies. Similarly to a multiplexing circuit used for multi-anode PMT, grounding and branching resistors were connected to each SiPM output channel. The grounding resistor was used to simultaneously reduce the signal crosstalk among different channels and to improve timing performance. Both grounding and branching resistor values were optimized to maintain a balanced performance of the event energy, timing, and positioning. A multiplexing circuit was implemented on a compact PCB and applied for a flat-panel detector which consisted of a 32×32 LYSO scintillator crystals optically coupled to 5×5 SiPM arrays for a total 20×20 output channels. Test results showed excellent crystal identification for all 1024 LYSO crystals (each with 2×2×30 mm3 size) with 22Na flood-source irradiation. The measured peak-to-valley ratio from typical crystal map profile is around 3:1 to 6.6:1, an average single crystal energy resolution of about 17.3%, and an average single crystal timing resolution of about 2 ns. Timing shift among different crystals, as reported in some other resistor-based multiplexing circuit designs, was not observed. In summary, we have designed and implemented a practical resistor-based multiplexing circuit that can be readily applied for reading out a large SiPM array with good detector performance.

In-beam PET imaging for on-line adaptive proton therapy: an initial phantom study.

We developed and investigated a positron emission tomography (PET) system for use with on-line (both in-beam and intra-fraction) image-guided adaptive proton therapy applications. The PET has dual rotating depth-of-interaction measurable detector panels by using solid-state photomultiplier (SSPM) arrays and LYSO scintillators. It has a 44 mm diameter trans-axial and 30 mm axial field-of-view (FOV). A 38 mm diameter polymethyl methacrylate phantom was placed inside the FOV. Both PET and phantom axes were aligned with a collimated 179.2 MeV beam. Each beam delivered ∼50 spills (0.5 s spill and 1.5 s inter-spill time, 3.8 Gy at Bragg peak). Data from each beam were acquired with detectors at a given angle. Nine datasets for nine beams with detectors at nine different angles over 180° were acquired for full-tomographic imaging. Each dataset included data both during and 5 min after irradiations. The positron activity-range was measured from the PET image reconstructed from all nine datasets and compared to the results from simulated images. A (22)Na disc-source was also imaged after each beam to monitor the PET system's performance. PET performed well except for slight shifts of energy photo-peak positions (<1%) after each beam, due mainly to the neutron exposure of SSPM that increased the dark-count noise. This minor effect was corrected offline with a shifting 350-650 keV energy window for each dataset. The results show a fast converging of activity-ranges measured by the prototype PET with high sensitivity and uniform resolution. Sub-mm activity-ranges were achieved with minimal 6 s acquisition time and three spill irradiations. These results indicate the feasibility of PET for intra-fraction beam-range verification. Further studies are needed to develop and apply a novel clinical PET system for on-line image-guided adaptive proton therapy.

Development of a prototype PET scanner with depth-of-interaction measurement using solid-state photomultiplier arrays and parallel readout electronics.

In this study, we developed a prototype animal PET by applying several novel technologies to use solid-state photomultiplier (SSPM) arrays to measure the depth of interaction (DOI) and improve imaging performance. Each PET detector has an 8 × 8 array of about 1.9 × 1.9 × 30.0 mm(3) lutetium-yttrium-oxyorthosilicate scintillators, with each end optically connected to an SSPM array (16 channels in a 4 × 4 matrix) through a light guide to enable continuous DOI measurement. Each SSPM has an active area of about 3 × 3 mm(2), and its output is read by a custom-developed application-specific integrated circuit to directly convert analogue signals to digital timing pulses that encode the interaction information. These pulses are transferred to and are decoded by a field-programmable gate array-based time-to-digital convertor for coincident event selection and data acquisition. The independent readout of each SSPM and the parallel signal process can significantly improve the signal-to-noise ratio and enable the use of flexible algorithms for different data processes. The prototype PET consists of two rotating detector panels on a portable gantry with four detectors in each panel to provide 16 mm axial and variable transaxial field-of-view (FOV) sizes. List-mode ordered subset expectation maximization image reconstruction was implemented. The measured mean energy, coincidence timing and DOI resolution for a crystal were about 17.6%, 2.8 ns and 5.6 mm, respectively. The measured transaxial resolutions at the center of the FOV were 2.0 mm and 2.3 mm for images reconstructed with and without DOI, respectively. In addition, the resolutions across the FOV with DOI were substantially better than those without DOI. The quality of PET images of both a hot-rod phantom and mouse acquired with DOI was much higher than that of images obtained without DOI. This study demonstrates that SSPM arrays and advanced readout/processing electronics can be used to develop a practical DOI-measureable PET scanner.

Energy and Timing Measurement with Time-Based Detector Readout for PET Applications: Principle and Validation with Discrete Circuit Components.

A new signal processing method for PET application has been developed, with discrete circuit components to measure energy and timing of a gamma interaction based solely on digital timing processing without using an amplitude-to-digital convertor (ADC) or a constant fraction discriminator (CFD). A single channel discrete component time-based readout (TBR) circuit was implemented in a PC board. Initial circuit functionality and performance evaluations have been conducted. Accuracy and linearity of signal amplitude measurement were excellent, as measured with test pulses. The measured timing accuracy from test pulses reached to less than 300 ps, a value limited mainly by the timing jitter of the prototype electronics circuit. Both suitable energy and coincidence timing resolutions (~18% and ~1.0 ns) have been achieved with 3 × 3 × 20 mm(3) LYSO scintillator and photomultiplier tube-based detectors. With its relatively simple circuit and low cost, TBR is expected to be a suitable front-end signal readout electronics for compact PET or other radiation detectors requiring the reading of a large number of detector channels and demanding high performance for energy and timing measurement.

Development of an Eight-Channel Time-Based Readout ASIC for PET Applications.

An eight-channel readout ASIC has been developed for reading output signals from solid-state photomultipliers for positron emission tomography applications. This ASIC converts both the signal charge and occurring time to digital timing pulses so that only a time-to-digital converter is required for further signal processing. This provides the advantages of simplified circuit design, reduced power consumption, and suitability for applications that have a large number of readout channels. The ASIC uses a fully current mode preamplifier to achieve high bandwidth (> 100 MHz), high time resolution (better than ~1 ns FWHM), and low power consumption (a few mW/ch). The linear dynamic range of charge measurement is adjustable and can be extended up to 103 pC. The chip has been fabricated with 0.35 µm 2P4M CMOS technology. A test prototype board has been developed and used for ASIC functionality and performance evaluation. Our preliminary studies show that the targets have been successfully achieved.