Guen Bae Ko

Dual-Phase Tapped-Delay-Line Time-to-Digital Converter With On-the-Fly Calibration Implemented in 40 nm FPGA

This paper describes two novel time-to-digital converter (TDC) architectures. The first is a dual-phase tapped-delay-line (TDL) TDC architecture that allows us to minimize the clock skew problem that causes the highly nonlinear characteristics of the TDC. The second is a pipelined on-the-fly calibration architecture that continuously compensates the nonlinearity and calibrates the fine times using the most up-to-date bin widths without additional dead time. The two architectures were combined and implemented in a single Virtex-6 device (ML605, Xilinx) for time interval measurement. The standard uncertainty for the time intervals from 0 to 20 ns was less than 12.83 ps-RMS (root mean square). The resolution (i.e., the least significant bit, LSB) of the TDC was approximately 10 ps at room temperature. The differential nonlinearity (DNL) values were [-1.0, 1.91] and [-1.0, 1.88] LSB and the integral nonlinearity (INL) values were [-2.20, 2.60] and [-1.63, 3.93] LSB for the two different TDLs that constitute one TDC channel. During temperature drift from 10 to 50°C, the TDC with on-the-fly calibration maintained the standard uncertainty of 11.03 ps-RMS.

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging

Visualization of biologic processes at molecular and cellular levels has revolutionized the understanding and treatment of human diseases. However, no single biomedical imaging modality provides complete information, resulting in the emergence of multimodal approaches. Combining state-of-the-art PET and MRI technologies without loss of system performance and overall image quality can provide opportunities for new scientific and clinical innovations. Here, we present a multiparametric PET/MR imager based on a small-animal dedicated, high-performance, silicon photomultiplier (SiPM) PET system and a 7-T MR scanner. Methods: A SiPM-based PET insert that has the peak sensitivity of 3.4% and center volumetric resolution of 1.92/0.53 mm3 (filtered backprojection/ordered-subset expectation maximization) was developed. The SiPM PET insert was placed between the mouse body transceiver coil and gradient coil of a 7-T small-animal MRI scanner for simultaneous PET/MRI. Mutual interference between the MRI and SiPM PET systems was evaluated using various MR pulse sequences. A cylindric corn oil phantom was scanned to assess the effects of the SiPM PET on the MR image acquisition. To assess the influence of MRI on the PET imaging functions, several PET performance indicators including scintillation pulse shape, flood image quality, energy spectrum, counting rate, and phantom image quality were evaluated with and without the application of MR pulse sequences. Simultaneous mouse PET/MRI studies were also performed to demonstrate the potential and usefulness of the multiparametric PET/MRI in preclinical applications. Results: Excellent performance and stability of the PET system were demonstrated, and the PET/MRI combination did not result in significant image quality degradation of either modality. Finally, simultaneous PET/MRI studies in mice demonstrated the feasibility of the developed system for evaluating the biochemical and cellular changes in a brain tumor model and facilitating the development of new multimodal imaging probes. Conclusion: We developed a multiparametric imager with high physical performance and good system stability and demonstrated its feasibility for small-animal experiments, suggesting its usefulness for investigating in vivo molecular interactions of metabolites, and cross-validation studies of both PET and MRI.

A novel compensation method for the anode gain non-uniformity of multi-anode photomultiplier tubes

The position-sensitive multi-anode photomultiplier tube (MA-PMT) is widely used in high-resolution scintillation detectors. However, the anode gain nonuniformity of this device is a limiting factor that degrades the intrinsic performance of the detector module. The aim of this work was to develop a gain compensation method for the MA-PMT and evaluate the resulting enhancement in the performance of the detector. The method employs a circuit that is composed only of resistors and is placed between the MA-PMT and a resistive charge division network (RCN) used for position encoding. The goal of the circuit is to divide the output current from each anode, so the same current flows into the RCN regardless of the anode gain. The current division is controlled by the combination of a fixed-value series resistor with an output impedance that is much larger than the input impedance of the RCN, and a parallel resistor, which detours part of the current to ground. PSpice simulations of the compensation circuit and the RCN were performed to determine optimal values for the compensation resistors when used with Hamamatsu H8500 MAPMTs. The intrinsic characteristics of a detector module consisting of this MA-PMT and a lutetium-gadolinium-oxyorthosilicate (LGSO) crystal array were tested with and without the gain compensation method. In simulation, the average coefficient of variation and max/min ratio decreased from 15.7% to 2.7% and 2.0 to 1.2, respectively. In the flood map of the LGSO-H8500 detector, the uniformity of the photopeak position for individual crystals and the energy resolution were much improved. The feasibility of the method was shown by applying it to an octagonal prototype positron emission tomography scanner.

Performance characterization of high quantum efficiency metal package photomultiplier tubes for time-of-flight and high-resolution PET applications

PURPOSE Metal package photomultiplier tubes (PMTs) with a metal channel dynode structure have several advanced features for devising such time-of-flight (TOF) and high spatial resolution positron emission tomography (PET) detectors, thanks to their high packing density, large effective area ratio, fast time response, and position encoding capability. Here, we report on an investigation of new metal package PMTs with high quantum efficiency (QE) for high-resolution PET and TOF PET detector modules. METHODS The latest metal package PMT, the Hamamatsu R11265 series, is served with two kinds of photocathodes that have higher quantum efficiency than normal bialkali (typical QE ≈ 25%), super bialkali (SBA; QE ≈ 35%), and ultra bialkali (UBA; QE ≈ 43%). In this study, the authors evaluated the performance of the new PMTs with SBA and UBA photocathodes as a PET detector by coupling various crystal arrays. They also investigated the performance improvements of high QE, focusing in particular on a block detector coupled with a lutetium-based scintillator. A single 4 × 4 × 10 mm(3) LYSO, a 7 × 7 array of 3 × 3 × 20 mm(3) LGSO, a 9 × 9 array of 1.2 × 1.2 × 10 mm(3) LYSO, and a 6 × 6 array of 1.5 × 1.5 × 7 mm(3) LuYAP were used for evaluation. All coincidence data were acquired with a DRS4 based fast digitizer. RESULTS This new PMT shows promising crystal positioning accuracy, energy and time discrimination performance for TOF, and high-resolution PET applications. The authors also found that a metal channel PMT with SBA was enough for both TOF and high-resolution application, although UBA gave a minor improvement to time resolution. However, significant performance improvement was observed in relative low light output crystals (LuYAP) coupled with UBA. CONCLUSIONS The results of this study will be of value as a useful reference to select PMTs for high-performance PET detectors.

Evaluation of a silicon photomultiplier PET insert for simultaneous PET and MR imaging

PURPOSE In this study, the authors present a silicon photomultiplier (SiPM)-based positron emission tomography (PET) insert dedicated to small animal imaging with high system performance and robustness to temperature change. METHODS The insert consists of 64 LYSO-SiPM detector blocks arranged in 4 rings of 16 detector blocks to yield a ring diameter of 64 mm and axial field of view of 55 mm. Each detector block consists of a 9 × 9 array of LYSO crystals (1.2 × 1.2 × 10 mm(3)) and a monolithic 4 × 4 SiPM array. The temperature of each monolithic SiPM is monitored, and the proper bias voltage is applied according to the temperature reading in real time to maintain uniform performance. The performance of this PET insert was characterized using National Electrical Manufacturers Association NU 4-2008 standards, and its feasibility was evaluated through in vivo mouse imaging studies. RESULTS The PET insert had a peak sensitivity of 3.4% and volumetric spatial resolutions of 1.92 (filtered back projection) and 0.53 (ordered subset expectation maximization) mm(3) at center. The peak noise equivalent count rate and scatter fraction were 42.4 kcps at 15.08 MBq and 16.5%, respectively. By applying the real-time bias voltage adjustment, an energy resolution of 14.2% ± 0.3% was maintained and the count rate varied ≤1.2%, despite severe temperature changes (10-30 °C). The mouse imaging studies demonstrate that this PET insert can produce high-quality images useful for imaging studies on the small animals. CONCLUSIONS The developed MR-compatible PET insert is designed for insertion into a narrow-bore magnetic resonance imaging scanner, and it provides excellent imaging performance for PET/MR preclinical studies.

A Feasibility Study on the Use of Optical Fibers for the Transfer of Scintillation Light to Silicon Photomultipliers

Integrated PET/MRI units with simultaneous acquisition capability are set to play an important role in studies of human breast and prostate imaging and brain function. However, to take advantage of existing MRI units in hospitals and institutions, minimally modified combined PET MRI is highly desirable. In addition, the current MRI trend is to utilize powerful body coils to transmit radio-frequency (RF) waves and local RF coils to receive signals. The authors propose a silicon photomultiplier (SiPM) PET equipped with optical fiber bundles that transfer photons from scintillation crystal to SiPM. To investigate the feasibility of SiPM PET using optical fiber bundles, the authors studied the performances of SiPM/scintillator couplings using single optical fibers and a fiber bundle. GEANT4 Monte-Carlo simulation was used to study scintillation photon transfer from scintillation crystals to the SiPM. This simulation showed that light loss, due to the bending of an optical fiber, is not significant for a fiber with a diameter of 2.0 mm and a bending radius of greater than 25 mm. To validate the GEANT4 Monte-Carlo simulation, several simple detectors were assembled and tested. Simulation results agreed reasonably well with experimental results. Two Hamamatsu multi-pixel photon counters (MPPCs) were tested using double clad optical fibers of 1.5 mm and 2.0 mm diameter, and 25 mm and 50 mm bending radius, respectively. When two MPPCs were directly attached to 2.0 × 2.0 × 10.0 mm3 LYSO crystals, a ~14% energy and a ~1.3 ns coincidence timing resolution were obtained at full width half maximum (FWHM). With one of the MPPCs attached to an optical fiber of 1.5 mm diameter, 50 mm bending radius, and length 300 mm, energy and coincidence timing resolutions were 27% and 2.2 ns, respectively. With an optical fiber bundle made of bare fibers with 1.5 mm diameter and length 100 mm, an ~ 26% energy resolution was obtained. Even though the Monte-Carlo simulation showed light loss was not significant for a single 90° turn of bending, the mechanical integrity of the optical fiber, especially the absence of cracks which can be caused by sharp bending, seemed to be a far more important constraint on sharp bending. These initial results are encouraging with respect to the use of combined SiPM PET using optical fibers.

Development and Performance Evaluation of a Time-of-Flight Positron Emission Tomography Detector Based on a High-Quantum-Efficiency Multi-Anode Photomultiplier Tube

We present the development and performance evaluation of time-of-flight (TOF) positron emission tomography (PET) detector modules designed for a proof-of-concept prototype of a TOF PET scanner based on the advanced high-quantum-efficiency (high-QE) multi-anode photomultiplier tube (PMT) (Hamamatsu H10966A-100 with super-bialkali photocathode) coupled with LGSO scintillation crystals (3 mm × 3 mm × 20 mm) whose cross section is smaller than that of crystals used in current clinical scanners. Compact dedicated front-end analog electronics combined with the high packing density and large effective area of the multi-anode PMT allow a modular detector design and thus a flexible and extendible geometry of the PET system. We optimized the electrical parameters (trigger threshold level, high voltage of PMTs, and amplifier gain) to yield the best timing resolution and acquired excellent flood map quality, energy resolution, and timing resolution with the optimal setup; the average distance-to-width ratio (DWR) of crystal peaks for 40 detectors was 5.3 ± 1.0, and the average energy resolution and coincidence resolving time (H10966A-100 vs. H10966A-100) were 11.04 ± 0.80% (FWHM) and 341 ± 45 ps (FWHM) respectively. The detector modules developed in this study and optimized their parameters to yield the best detector performance will be useful for the future development of the next generation TOF PET scanners based on them.

A Dual-Ended Readout Detector Using a Meantime Method for SiPM TOF-DOI PET

We have investigated a dual-ended readout detector based on two silicon photo-multipliers (SiPMs) using a 30 mm long cerium-doped lutetium-yttrium oxyorthosilicate ( Lu0.5Y1.4Si0.5:Ce, LYSO) crystal to study the feasibility of a time-of-flight (TOF) and depth-of-interaction (DOI) positron emission tomography (PET). To improve the timing resolution in the dual-ended readout detector, a novel meantime measurement was employed. The meantime was obtained by averaging two signal arrival times at two SiPMs, each of which was attached to both ends of the LYSO crystal. The meantime method minimizes the arrival time difference along the crystal. Both timing and DOI resolutions using the meantime method were better than those of a single-ended readout detector.

Prototype pre-clinical PET scanner with depth-of-interaction measurements using single-layer crystal array and single-ended readout

In this study, we developed a proof-of-concept prototype PET system using a pair of depth-of-interaction (DOI) PET detectors based on the proposed DOI-encoding method and digital silicon photomultiplier (dSiPM). Our novel cost-effective DOI measurement method is based on a triangular-shaped reflector that requires only a single-layer pixelated crystal and single-ended signal readout. The DOI detector consisted of an 18  ×  18 array of unpolished LYSO crystal (1.47  ×  1.47  ×  15 mm3) wrapped with triangular-shaped reflectors. The DOI information was encoded by depth-dependent light distribution tailored by the reflector geometry and DOI correction was performed using four-step depth calibration data and maximum-likelihood (ML) estimation. The detector pair and the object were placed on two motorized rotation stages to demonstrate 12-block ring PET geometry with 11.15 cm diameter. Spatial resolution was measured and phantom and animal imaging studies were performed to investigate imaging performance. All images were reconstructed with and without the DOI correction to examine the impact of our DOI measurement. The pair of dSiPM-based DOI PET detectors showed good physical performances respectively: 2.82 and 3.09 peak-to-valley ratios, 14.30% and 18.95% energy resolution, and 4.28 and 4.24 mm DOI resolution averaged over all crystals and all depths. A sub-millimeter spatial resolution was achieved at the center of the field of view (FOV). After applying ML-based DOI correction, maximum 36.92% improvement was achieved in the radial spatial resolution and a uniform resolution was observed within 5 cm of transverse PET FOV. We successfully acquired phantom and animal images with improved spatial resolution and contrast by using the DOI measurement. The proposed DOI-encoding method was successfully demonstrated in the system level and exhibited good performance, showing its feasibility for animal PET applications with high spatial resolution and sensitivity.

Single transmission-line readout method for silicon photomultiplier based time-of-flight and depth-of-interaction PET

We propose a novel single transmission-line readout method for whole-body time-of-flight positron emission tomography applications, without compromising on performance. The basic idea of the proposed multiplexing method is the addition of a specially prepared tag signal ahead of the scintillation pulse. The tag signal is a square pulse that encodes photon arrival time and channel information. The 2D position of a silicon photomultiplier (SiPM) array is encoded by the specific width and height of the tag signal. A summing amplifier merges the tag and scintillation signals of each channel, and the final output signal can be acquired with a one-channel digitizer. The feasibility and performance of the proposed method were evaluated using a 1:1 coupled detector consisting of 4  ×  4 array of LGSO crystals and 16 channel SiPM. The sixteen 3 mm LGSO crystals were clearly separated in the crystal-positioning map with high reliability. The average energy resolution and coincidence resolving time were 11.31  ±  0.55% and 264.7  ±  10.7 ps, respectively. We also proved that the proposed method does not degrade timing performance with increasing multiplexing ratio. The two types of LGSO crystals (L0.95GSO and L0.20GSO) in phoswich detector were also clearly identified with the high-reliability using pulse shape discrimination, thanks to the well-preserved pulse shape information. In conclusion, the proposed multiplexing method allows decoding of the 3D interaction position of gamma rays in the scintillation detector with single-line readout.