Kai Lou

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.

Capacitor based multiplexing circuit for silicon photomultiplier array readout

Several different multiplexing readout methods have been investigated for reading out silicon photomultiplier (SiPM) arrays. However, it is still challenging by using these methods to maintain signal integrity for overall good signal and imaging performance while reducing the number of readout and processing channels. One common issue to resistor based multiplexing method is the position-dependent timing shift among different channels, which can in principle be calibrated and corrected but add complexity to the detector calibration and operation process, and can be very difficult to apply for a practical PET system for routine imaging applications. To solve such and other problems, we explored a capacitor-based multiplexing method for our PET detector to read SiPM with a common cathode which has not been addressed previously. To achieve good detector performance, we required output signal without undershot/overshot suited for excellent charge integration, and without timing shift among different channels. The design applies a capacitor network to divide the charge of signals from a SiPM into two branches, with the division of charge based on the position of the SiPM in the network. Only one capacitor value is needed. The number of readout channels can be reduced from N×N to 2N. Evaluation circuit was tested with pulsed signals and a practical PET detector which consisted of an 8×8 SiPM array and LYSO scintillator array. The results showed that signal rise and fall times from different channels were the similar, no output signal undershot, and no timing shift among different channels. The resistive and capacitive multiplexing methods were compared for their noise level, energy resolution, rise time, and timing resolution as function of channel numbers. Capacitive multiplexing method shows better noise and timing performance with much better timing and energy consistent from all detector area. A PCB circuit board with capacitor multiplexing has been developed for PET detector applications.

WE‐EF‐303‐06: Feasibility of PET Image‐Based On‐Line Proton Beam‐Range Verification with Simulated Uniform Phantom and Human Brain Studies

Purpose: To study the feasibility of clinical on-line proton beam range verification with PET imaging Methods: We simulated a 179.2-MeV proton beam with 5-mm diameter irradiating a PMMA phantom of human brain size, which was then imaged by a brain PET with 300*300*100-mm^3 FOV and different system sensitivities and spatial resolutions. We calculated the mean and standard deviation of positron activity range (AR) from reconstructed PET images, with respect to different data acquisition times (from 5 sec to 300 sec with 5-sec step). We also developed a technique, “Smoothed Maximum Value (SMV)”, to improve AR measurement under a given dose. Furthermore, we simulated a human brain irradiated by a 110-MeV proton beam of 50-mm diameter with 0.3-Gy dose at Bragg peak and imaged by the above PET system with 40% system sensitivity at the center of FOV and 1.7-mm spatial resolution. Results: MC Simulations on the PMMA phantom showed that, regardless of PET system sensitivities and spatial resolutions, the accuracy and precision of AR were proportional to the reciprocal of the square root of image count if image smoothing was not applied. With image smoothing or SMV method, the accuracy and precision could be substantially improved. For a cylindrical PMMA phantom (200 mm diameter and 290 mm long), the accuracy and precision of AR measurement could reach 1.0 and 1.7 mm, with 100-sec data acquired by the brain PET. The study with a human brain showed it was feasible to achieve sub-millimeter accuracy and precision of AR measurement with acquisition time within 60 sec. Conclusion: This study established the relationship between count statistics and the accuracy and precision of activity-range verification. It showed the feasibility of clinical on-line BR verification with high-performance PET systems and improved AR measurement techniques. Cancer Prevention and Research Institute of Texas grant RP120326, NIH grant R21CA187717, The Cancer Center Support (Core) Grant CA016672 to MD Anderson Cancer Center

Development of compact DOI-measurable PET detectors for simultaneous PET/MR Imaging

It is critically needed yet challenging to develop compact PET detectors with high sensitivity and uniform, high imaging resolution for improving the performance of simultaneous PET/MR imaging, particularly for an integrated/inserted small-bore system. Using the latest “edge-less” SiPM arrays for DOI measurement using the design of dual-ended-scintillator readout, we developed several compact PET detectors suited for PET/MR imaging. Each detector consists of one LYSO array with each end coupled to a SiPM array. Multiple detectors can be seamlessly tiled together along all sides to form a large detector panel. Detectors with 1.5x1.5 and 2.0x2.0 mm crystals at 20 or 30 mm lengths were studied. Readout of individual SiPM or capacitor-based signal multiplexing was used to transfer 3D interaction position-coded analog signals through flexible-print-circuit cables to dedicated ASIC frontend electronics to output digital timing pulses that encode interaction information. These digital pulses can be transferred to, through standard LVDS cables, and decoded by a FPGA-based data acquisition positioned outside the MRI scanner for coincidence event selection. Initial detector performance measurement shows excellent crystal identification even with 30 mm long crystals, ~18% and 2.8 ns energy and timing resolutions, and around 2-3 mm DOI resolution. A large size detector panel can be scaled up with these modular detectors and different PET systems can be flexibly configured with the scalable readout electronics and data acquisition, providing an important design advantage for different system and application requirements. It is expected that standard shielding of detectors, electronics and signal transfer lines can be applied for simultaneous PET/MR imaging applications, with desired DOI measurement capability to enhance the PET performance and image quality.

Monte Carlo simulation based scatter correction in 3D list-mode image reconstruction

We developed a Monte Carlo simulation based scatter correction method for 3D list-mode image reconstruction, and tested the method with Monte Carlo simulations. First, an emission image without scatter correction was reconstructed using MLEM. A transmission image was generated with the CT image. Then, based on the emission and transmission images, GATE was used to simulate coincidence events with their line-of responses (LORs) grouped according to their spatial positions (e.g. interaction positions or detector modules). The scatter ratio (scatter vs total coincidences) in each LOR group was calculated and stored in a scatter table. Finally, the scatter table was applied in a new image reconstruction to correct the scatter on the basis of each LOR group. The method was implemented in a simulated brain-size PET, with 300×300×100 mm3 FOV, 2×2×30 mm3 LYSO crystals, and 5 mm depth-of-interaction (DOI) resolution. Images of a 150×150×80 mm3 PMMA phantom inserted with three different radioisotope distributions were studied, including a point source array, a hot rod matrix, and a uniform source. We used detector module as the criteria to group LORs. With scatter correction, image resolution was almost the same as measured by point sources at different FOV positions; hot-rod sources showed visually improved image quality with reduced background noise; image SNR of the uniform source was not impacted. This method has been successfully implemented in the brain-size PET with improved image quality. It can be potentially applied to other list-mode 3D PET systems, with considering the accuracy and variation of scatter ratio in LOR grouping.

Design and development of novel and practical PET detectors for advanced imaging applications

New DOI-measurable PET detectors have been designed, developed and evaluated with advanced silicon photomultiplier (SiPM) and readout technologies. The detector consists of an 8×8 array of 1.5×1.5×20 or 1.5×1.5×30 mm3 LYSO scintillators which is optically coupled to a 4×4 array of 3×3 mm2 SiPM array at each crystal array end through a 2 mm thick optical plate. Scintillator surfaces, reflectors and coupling were designed and fabricated to reserve the air-gap to achieve high depth-of-interaction (DOI) resolution and other detection performance. The insensitive edges around each detector is less than 0.2 mm, making it practical to seamlessly tile detectors together to assemble a large size detector panel for developing a PET system. A 16-ch ASIC based PCB readout electronics was developed to solve the challenging SiPM array readout problem. Each compact PCB contains 4 ASIC chips and one detector-level FPGA, with analog signal being inputted from each SiPM array through a flexible printed circuit cable, converted to digital timing pulses, processed online by FPGA to record interaction information (energy, timing, and position), and transferred through a fast LVDS connection to system FPGA for event selection and data acquisition. Initial measurements showed excellent crystal identification with all crystals were clearly separated from each other in a flood source image, with resolutions of energy, timing and DOI were around 17%, 2.7 ns and 2.0 mm (mean value), respectively. Overall, comparing to the previous prototype DOI detectors we developed, the new detector is simplified in design without using complicated light guide yet with significantly improved DOI resolution (from ~5 to ~2 mm), more compact packaging for making a large size flat-panel detector, and more integrated and fast readout electronics. The new detector and readout is expected leading to an advanced PET with leapfrog imaging performance improvement.

SU‐E‐J‐82: Intra‐Fraction Proton Beam‐Range Verification with PET Imaging: Feasibility Studies with Monte Carlo Simulations and Statistical Modeling

PURPOSE To study the feasibility of intra-fraction proton beam-range verification with PET imaging. METHODS Two phantoms homogeneous cylindrical PMMA phantoms (290 mm axial length, 38 mm and 200 mm diameter respectively) were studied using PET imaging: a small phantom using a mouse-sized PET (61 mm diameter field of view (FOV)) and a larger phantom using a human brain-sized PET (300 mm FOV). Monte Carlo (MC) simulations (MCNPX and GATE) were used to simulate 179.2 MeV proton pencil beams irradiating the two phantoms and be imaged by the two PET systems. A total of 50 simulations were conducted to generate 50 positron activity distributions and correspondingly 50 measured activity-ranges. The accuracy and precision of these activity-ranges were calculated under different conditions (including count statistics and other factors, such as crystal cross-section). Separate from the MC simulations, an activity distribution measured from a simulated PET image was modeled as a noiseless positron activity distribution corrupted by Poisson counting noise. The results from these two approaches were compared to assess the impact of count statistics on the accuracy and precision of activity-range calculations. RESULTS MC Simulations show that the accuracy and precision of an activity-range are dominated by the number (N) of coincidence events of the reconstructed image. They are improved in a manner that is inversely proportional to 1/sqrt(N), which can be understood from the statistical modeling. MC simulations also indicate that the coincidence events acquired within the first 60 seconds with 10^9 protons (small phantom) and 10^10 protons (large phantom) are sufficient to achieve both sub-millimeter accuracy and precision. CONCLUSION Under the current MC simulation conditions, the initial study indicates that the accuracy and precision of beam-range verification are dominated by count statistics, and intra-fraction PET image-based beam-range verification is feasible. This work was supported by a research award RP120326 from Cancer Prevention and Research Institute of Texas.

MO-G-17A-01: Innovative High-Performance PET Imaging System for Preclinical Imaging and Translational Researches.

PURPOSE To develop a practical and compact preclinical PET with innovative technologies for substantially improved imaging performance required for the advanced imaging applications. METHODS Several key components of detector, readout electronics and data acquisition have been developed and evaluated for achieving leapfrogged imaging performance over a prototype animal PET we had developed. The new detector module consists of an 8×8 array of 1.5×1.5×30 mm3 LYSO scintillators with each end coupled to a latest 4×4 array of 3×3 mm2 Silicon Photomultipliers (with ∼0.2 mm insensitive gap between pixels) through a 2.0 mm thick transparent light spreader. Scintillator surface and reflector/coupling were designed and fabricated to reserve air-gap to achieve higher depth-of-interaction (DOI) resolution and other detector performance. Front-end readout electronics with upgraded 16-ch ASIC was newly developed and tested, so as the compact and high density FPGA based data acquisition and transfer system targeting 10M/s coincidence counting rate with low power consumption. The new detector module performance of energy, timing and DOI resolutions with the data acquisition system were evaluated. Initial Na-22 point source image was acquired with 2 rotating detectors to assess the system imaging capability. RESULTS No insensitive gaps at the detector edge and thus it is capable for tiling to a large-scale detector panel. All 64 crystals inside the detector were clearly separated from a flood-source image. Measured energy, timing, and DOI resolutions are around 17%, 2.7 ns and 1.96 mm (mean value). Point source image is acquired successfully without detector/electronics calibration and data correction. CONCLUSION Newly developed advanced detector and readout electronics will be enable achieving targeted scalable and compact PET system in stationary configuration with >15% sensitivity, ∼1.3 mm uniform imaging resolution, and fast acquisition counting rate capability for substantially improved imaging and quantification performance for small animal imaging and image-guided radiotherapy applications. This work was supported by a research award RP120326 from Cancer Prevention and Research Institute of Texas.

Monte Carlo simulation study of in-beam intra-treatment PET imaging for adaptive proton therapy

We conducted Monte Carlo simulations to investigate the feasibility of the proton beam-range verification with few beam spills before the start of treatment to provide rapid feedback for treatment plan verification and re-planning (if necessary) for improving the accuracy of treatment targeting: a potentially novel intra-treatment image-guided adaptive proton therapy. MCNPX package was used to generate the distributions of positron emitters in a uniform cylinder PMMA phantom irradiated by a collimated 180 MeV pristine proton beam. Two PET systems, a small dual-panel rotational PET and a stationary brain PET, with depth-of-interaction (DOI) measurement, were simulated with GATE for imaging. The images were reconstructed with list-mode MLEM algorithm using simulated coincidence data accumulated during- and post-irradiations. Positron activity-ranges were measured as a function of number of beam spills, total acquisition time, crystal cross-section size, crystal length, and the number of coincidence events. Results show that the accuracy of activity-range measurement is a function of data statistics but converging rapidly within few beam spills under simulated conditions; few spills can be sufficient to measure the activity-range within 1.0 mm from the final converged value; the number of spills can be further reduced if acquiring 30-60 sec post-irradiation data, which is still considered a rapid intra-treatment imaging. The accuracy and precision of activity-range measurement was also calculated as a function of count statistics under the simulated conditions, providing a general and very useful guideline to calculate the required statistics for an accurate intra-treatment “in-beam” activity-range measurement.

WE‐G‐500‐03: In‐Beam PET Imaging with Depth‐Of‐Interaction Measurement for Accurate Proton Beam‐Range Verification

PURPOSE To study the feasibility of using an in-beam PET with depth-of-interaction (DOI) measurement to improve beam-range verification for proton therapy. METHODS A compact prototype PET with dual rotating DOI-measurable detector panels was developed based on using solid-state photomultiplier (SSPM) arrays to read LYSO scintillators with parallel readout ASIC electronics. The system had a 44mm diameter trans-axial and 30mm-axial field of view (FOV). A 36mm diameter PMMA phantom was placed inside FOV. Both PET and phantom axes were aligned with collimated 200 MeV beams. The Bragg peak was located within the axial FOV by adjusting phantom position. A total of 9 beams irradiated the phantom with a 20-40 minutes beam separation; each beam delivered ∼50 spills (0.5 sec spill and 1.5 sec inter-spill time, 800 MU); data from each beam were acquired with detectors at a certain angle; 9 datasets for 9 beams with detectors at 9 different angles over 180o were acquired; each dataset collected both in-beam and 5 min after-beam data. Beam-range was measured from the PET image reconstructed from all 9 datasets, and compared to the results from simulated images. Additionally, a Na-22 disk-source was also acquired after each beam to measure the impact of neutrons on system performance. RESULTS PET performed well except energy photo-peak positions were reduced slightly after each beam, presumably secondary to neutron exposure of the SSPM. This minor effect was corrected with a shifting 350-650 keV energy window for each dataset. The difference between measured and simulated beam-ranges was within 1.0 mm, and this can be achieved with in-beam data alone. DOI-measurement provided uniform resolutions and high sensitivity to improve the accuracy of range verification. CONCLUSION A SSPM-based DOI-measureable PET capable of in-beam imaging may offer significant improvements in the accuracy of proton beam-range verification. This project is supported by award RP120326 from the Cancer Prevention & Research Institute of Texas.