Doctor of Philosophy, Seoul National University (2018)
Bachelor of Engineering, Seoul National University (2012)
Whole-Body Voxel-Based Personalized Dosimetry: The Multiple Voxel S-Value Approach for Heterogeneous Media with Nonuniform Activity Distributions
JOURNAL OF NUCLEAR MEDICINE
2018; 59 (7): 1133–39
Personalized dosimetry with high accuracy is becoming more important because of the growing interest in personalized medicine and targeted radionuclide therapy. Voxel-based dosimetry using dose point kernel or voxel S-value (VSV) convolution is available. However, these approaches do not consider the heterogeneity of the medium. Here, we propose a new method for whole-body voxel-based personalized dosimetry in heterogeneous media with nonuniform activity distributions-a method we refer to as the multiple VSV approach. Instead of using only a single VSV, as found in water, the method uses multiple numbers (N) of VSVs to cover media of various density ranges, as found in the whole body. Methods: The VSVs were precalculated using GATE Monte Carlo simulation and were convoluted with the time-integrated activity to generate density-specific dose maps. CT-based segmentation was performed to generate a binary mask image for each density region. The final dose map was acquired by the summation of N segmented density-specific dose maps. We tested several sets of VSVs with different densities: N = 1 (single water VSV), 4, 6, 8, 10, and 20. To validate the proposed method, phantom and patient studies were conducted and compared with the direct Monte Carlo approach, which was considered the ground truth. Finally, dosimetry on 10 patients was performed using the multiple VSV approach and compared with the single VSV and organ-based approaches. Errors at the voxel and organ levels were reported for 8 organs. Results: In the phantom and patient studies, the multiple VSV approach showed significant decreases in voxel-level errors, especially for the lung and bone regions. As the number of VSVs increased, voxel-level errors decreased, although some overestimations were observed at the lung boundaries. For the multiple VSVs (N = 8), we achieved a voxel-level error of 2.06%. In the dosimetry study, our proposed method showed greatly improved results compared with single VSV and organ-based dosimetry. Errors at the organ level were -6.71%, 2.17%, and 227.46% for single VSV, multiple VSV, and organ-based dosimetry, respectively. Conclusion: The multiple VSV approach for heterogeneous media with nonuniform activity distributions offers fast personalized dosimetry at the whole-body level, yielding results comparable to those of the direct Monte Carlo approach.
View details for DOI 10.2967/jnumed.117.201095
View details for Web of Science ID 000437237200034
View details for PubMedID 29242397
Novel inter-crystal scattering event identification method for PET detectors
PHYSICS IN MEDICINE AND BIOLOGY
2018; 63 (11): 115015
Here, we propose a novel method to identify inter-crystal scattering (ICS) events from a PET detector that is even applicable to light-sharing designs. In the proposed method, the detector observation was considered as a linear problem and ICS events were identified by solving this problem. Two ICS identification methods were suggested for solving the linear problem, pseudoinverse matrix calculation and convex constrained optimization. The proposed method was evaluated based on simulation and experimental studies. For the simulation study, an 8 × 8 photo sensor was coupled to 8 × 8, 10 × 10 and 12 × 12 crystal arrays to simulate a one-to-one coupling and two light-sharing detectors, respectively. The identification rate, the rate that the identified ICS events correctly include the true first interaction position and the energy linearity were evaluated for the proposed ICS identification methods. For the experimental study, a digital silicon photomultiplier was coupled with 8 × 8 and 10 × 10 arrays of 3 × 3 × 20 mm3 LGSO crystals to construct the one-to-one coupling and light-sharing detectors, respectively. Intrinsic spatial resolutions were measured for two detector types. The proposed ICS identification methods were implemented, and intrinsic resolutions were compared with and without ICS recovery. As a result, the simulation study showed that the proposed convex optimization method yielded robust energy estimation and high ICS identification rates of 0.93 and 0.87 for the one-to-one and light-sharing detectors, respectively. The experimental study showed a resolution improvement after recovering the identified ICS events into the first interaction position. The average intrinsic spatial resolutions for the one-to-one and light-sharing detector were 1.95 and 2.25 mm in the FWHM without ICS recovery, respectively. These values improved to 1.72 and 1.83 mm after ICS recovery, respectively. In conclusion, our proposed method showed good ICS identification in both one-to-one coupling and light-sharing detectors. We experimentally validated that the ICS recovery based on the proposed identification method led to an improved resolution.
View details for DOI 10.1088/1361-6560/aabe3a
View details for Web of Science ID 000434760000005
View details for PubMedID 29658493
Prototype pre-clinical PET scanner with depth-of-interaction measurements using single-layer crystal array and single-ended readout
PHYSICS IN MEDICINE AND BIOLOGY
2017; 62 (10): 3983–96
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.
View details for DOI 10.1088/1361-6560/aa64c7
View details for Web of Science ID 000399434100006
View details for PubMedID 28406795
Depth-of-interaction measurement in a single-layer crystal array with a single-ended readout using digital silicon photomultiplier
PHYSICS IN MEDICINE AND BIOLOGY
2015; 60 (16): 6495–6514
We present the first experimental evaluation of a depth-of-interaction (DOI) positron emission tomography (PET) detector using a digital silicon photomultiplier (dSiPM). To measure DOI information from a mono-layer array of scintillation crystals with a single-ended readout, our group has previously proposed and developed a new method based on light spread using triangular reflectors. Since this method relies on measurement of the light distribution, dSiPM, which has a fully digital interface, has several merits for our DOI measurement. The DOI PET detector comprised of a dSiPM sensor (DPC-3200-22-44) coupled with a 14 × 14 array of 2 mm × 2 mm × 20 mm unpolished LGSO crystals. All crystals were covered with triangular reflectors. To obtain a good performance of the DOI PET detector, several parameters of detector were selected as a preliminary experiment. Detector performance was evaluated with the selected parameters and the optimal experimental setup, and a DOI measurement was conducted by irradiating the crystal block at five DOI positions spaced at intervals of 4 mm. Maximum-likelihood estimation was employed for DOI positioning and the optimal DOI estimation scheme was also investigated in this study. As a result, the DOI PET detector showed clear crystal identification. The energy resolution (full-width at half-maximum (FWHM)) averaged over all depths was 10.21% ± 0.15% at 511 keV, and time resolution averaged over all depths was 1198.61 ± 39.70 ps FWHM. The average DOI positioning accuracy for all depths was 74.22% ± 6.77%, which equates to DOI resolution of 4.67 mm. Energy and DOI resolutions were uniform over all crystal positions except for the back parts of the array. Furthermore, additional simulation studies were conducted to verify the results of our DOI measurement method that is combined with dSiPM technology. In conclusion, our continuous DOI PET detector coupled with dSiPM is a promising PET/MRI detector with DOI-encoding capability.
View details for DOI 10.1088/0031-9155/60/16/6495
View details for Web of Science ID 000361052600021
View details for PubMedID 26247294
Tumor-associated macrophages enhance tumor hypoxia and aerobic glycolysis.
Tumor hypoxia and aerobic glycolysis are well-known resistance factors for anticancer therapies. Here we demonstrate that tumor-associated macrophages (TAM) enhance tumor hypoxia and aerobic glycolysis in mice subcutaneous tumors and in non-small cell lung cancer (NSCLC) patients. We found a strong correlation between CD68 TAM immunostaining and positron emission tomography (PET) 18fluoro-deoxyglucose (FDG) uptake in 98 matched tumors of NSCLC patients. We also observed a significant correlation between CD68 and glycolytic gene signatures in 513 NSCLC patients from the TCGA database. TAM secreted tumor necrosis factor-alpha (TNF-alpha) to promote tumor cell glycolysis while increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) in TAM facilitated tumor hypoxia. Depletion of TAM by clodronate was sufficient to abrogate aerobic glycolysis and tumor hypoxia, thereby improving tumor response to anticancer therapies. TAM depletion led to a significant increase in programmed death-ligand 1 (PD-L1) expression in aerobic cancer cells as well as T cell infiltration in tumors, resulting in antitumor efficacy by PD-L1 antibodies which were otherwise completely ineffective. These data suggest that TAM can significantly alter tumor metabolism, further complicating tumor response to anticancer therapies including immunotherapy.
View details for PubMedID 30610087
Systematic study on factors influencing the performance of interdetector scatter recovery in small-animal PET
2018; 45 (8): 3551–62
Interdetector scatter (IDS) is a triple coincidence caused by the Compton scatter of an annihilation photon from one detector block to another which frequently occurs in small-animal positron emission tomography (PET). By finding the true lines-of-response (LORs) of annihilation photon pairs among three possible LORs in IDS events, we can utilize these recovered events to improve the sensitivity of PET systems. IDS recovery should be accurate to yield reliable images with relatively short scan times. We systemically investigated physical factors affecting IDS recovery performance, focusing on the reconstructed image quality of small-animal PET. We evaluated sensitivity increase, recovery accuracy, and image quality by applying different combinations of energy window, recovery scheme, and scanner properties.We used GATE Monte Carlo simulation to acquire coincidence events from a NEMA NU 4-2008 image quality phantom using small-animal PET scanner with axial field of view of 55 mm and diameter of 64 mm. We first defined energy window criteria to obtain valid IDS events. Their role was to assign triple coincidences as IDS events and to restrict the number of LOR candidates to two. We tested three different energy windows around 511 keV. Second, we applied four different recovery schemes (maximum energy, Compton kinematics, neural network, and proportional) to assigned IDS events. To measure the effects of scanner properties, energy resolutions of 0-20% and one to four depth-of-interaction (DOI) layers were simulated. For every combination of the factors, we measured sensitivity increase and recovery accuracy. We also analyzed the reconstructed images for each IDS recovery method in terms of mean pixel intensity, noise, signal-to-noise ratio (SNR), contrast, and recovery coefficients.Sensitivity increase depended on the energy window and energy resolution. The maximum increase in sensitivity was 33% when energy window of [250, 750] keV was applied. Higher energy resolution yielded larger sensitivity increase, especially for narrow windows. Recovery accuracy was affected by all the factors tested in this study. Accuracy increased with narrower energy window, and a neural network scheme was the most accurate. The better energy resolution and DOI capability improved accuracy by providing precise measurement of energies and interaction positions. In image quality analysis, noise and SNR were highly dependent on the sensitivity increase and energy window. When the same energy window was applied, SNR, contrast, and recovery coefficients were higher with higher accuracy of the scheme. Meanwhile, the proportional scheme yielded the best image quality among the schemes and reduced 20% of scan time to achieve the same SNR as that of double coincidence images.As a fundamental research for real implementation of IDS recovery, we conducted a simulation study to evaluate the factors affecting sensitivity increase, recovery accuracy, and image quality. Sensitivity increase was dependent on the energy window and energy resolution, while the recovery accuracy was affected by energy window, recovery scheme, energy resolution, and DOI capability. In image quality analysis, sensitivity increase and recovery accuracy dominantly affected the noise and quantitative accuracy, respectively. Among the recovery schemes, the proportional scheme obtained the best image quality.
View details for DOI 10.1002/mp.13020
View details for Web of Science ID 000441292000010
View details for PubMedID 29851131
Performance of a new accelerating-electrode-equipped fast-time-response PMT coupled with fast LGSO.
Physics in medicine and biology
2018; 63 (5): 05NT03
In this study, we measured the performance of a newly developed Hamamatsu Photonics R13478 photomultiplier tube (PMT) and compared the results with those of an existing R9800 PMT. In R13478, an accelerating electrode is placed between the focusing electrode and first dynode for time resolution improvement through reduced transit time jitter. We investigated the time resolution dependence on the supply voltage and time pickoff method for R13478 and R9800 PMTs, each coupled with a 2.9 × 2.9 × 20 mm3 fast LGSO:Ce (0.025 mol%) crystal. In addition, we measured the PMT time resolutions coupled with the crystals in edge and laid positions to determine the effects of the reduced position dependence of transit time in R13478. R13478 exhibited a better time performance than R9800 in various ways. The rise time of R13478 for our experimental setup was 1.54 ns, 100 ps shorter than that of R9800 because of the reduced transit time. Further, R13478 achieved a 169 ps single time resolution at the recommended supply voltage, while this value was 187 ps for R9800. The time resolution of R13478 was also significantly better for a low time pickoff threshold level and a high supplied voltage, which are conditions vulnerable to transit time jitter and noise, respectively. A considerable difference in time resolution was observed for the laid position (R13478: 144 ps; R9800: 167 ps), indicating that the accelerating electrode reduced spatial transit time difference. Overall, we showed the effects of the differentiated characteristics of R13478 PMT compared with R9800 and confirmed its excellent time performance. We suggest use of this device as a photodetector effective for fast timing applications such as time-of-flight positron emission tomography.
View details for DOI 10.1088/1361-6560/aaad20
View details for PubMedID 29405124
- Enzyme-Driven Hasselback-Like DNA-Based Inorganic Superstructures ADVANCED FUNCTIONAL MATERIALS 2017; 27 (45)
Proof-of-concept prototype time-of-flight PET system based on high-quantum-efficiency multianode PMTs
2017; 44 (10): 5314–24
Time-of-flight (TOF) information in positron emission tomography (PET) scanners enhances the diagnostic power of PET scans owing to the increased signal-to-noise ratio of reconstructed images. There are numerous additional benefits of TOF reconstruction, including the simultaneous estimation of activity and attenuation distributions from emission data only. Exploring further TOF gains by using TOF PET scanners is important because it can broaden the applications of PET scans and expand our understanding of TOF techniques. Herein, we present a prototype TOF PET scanner with fine-time performance that can experimentally demonstrate the benefits of TOF information.A single-ring PET system with a coincidence resolving time of 360 ps and a spatial resolution of 3.1/2.2 mm (filtered backprojection/ordered-subset expectation maximization) was developed. The scanner was based on advanced high-quantum-efficiency (high-QE) multianode photomultiplier tubes (PMTs). The impact of its fine-time performance was demonstrated by evaluating body phantom images reconstructed with and without TOF information. Moreover, the feasibility of the scanner as an experimental validator of TOF gains was verified by investigating the improvement of images under various conditions, such as the use of joint estimation algorithms of activity and attenuation, erroneous data correction factors (e.g., without normalization correction), and incompletely sampled data.The prototype scanner showed excellent performance, producing improved phantom images, when TOF information was employed in the reconstruction process. In addition, investigation of the TOF benefits using the phantom data in different conditions verified the usefulness of the developed system for demonstrating the practical effects of TOF reconstruction.We developed a prototype TOF PET scanner with good performance and a fine-timing resolution based on advanced high-QE multianode PMTs and demonstrated its feasibility as an experimental validator of TOF gains, suggesting its usefulness for investigating new applications of PET scans and clarifying TOF techniques in detail.
View details for DOI 10.1002/mp.12440
View details for Web of Science ID 000412901300038
View details for PubMedID 28665489
A depth-of-interaction PET detector using a stair-shaped reflector arrangement and a single-ended scintillation light readout
PHYSICS IN MEDICINE AND BIOLOGY
2017; 62 (2): 465–83
Positron emission tomography (PET) detectors with the ability to encode depth-of-interaction (DOI) information allow us to simultaneously improve the spatial resolution and sensitivity of PET scanners. In this study, we propose a DOI PET detector based on a stair-pattern reflector arrangement inserted between pixelated crystals and a single-ended scintillation light readout. The main advantage of the proposed method is its simplicity; DOI information is decoded from a flood map and the data can be simply acquired by using a single-ended readout system. Another potential advantage is that the two-step DOI detectors can provide the largest peak position distance in a flood map because two-dimensional peak positions can be evenly distributed. We conducted a Monte Carlo simulation and obtained flood maps. Then, we conducted experimental studies using two-step DOI arrays of 5 × 5 Lu1.9Y0.1SiO5:Ce crystals with a cross-section of 1.7 × 1.7 mm2 and different detector configurations: an unpolished single-layer (US) array, a polished single-layer (PS) array and a polished stacked two-layer (PT) array. For each detector configuration, both air gaps and room-temperature vulcanization (RTV) silicone gaps were tested. Detectors US and PT showed good peak separation in each scintillator with an average peak-to-valley ratio (PVR) and distance-to-width ratio (DWR) of 2.09 and 1.53, respectively. Detector PSRTV showed lower PVR and DWR (1.65 and 1.34, respectively). The configuration of detector PTAir is preferable for the construction of time-of-flight-DOI detectors because timing resolution was degraded by only about 40 ps compared with that of a non-DOI detector. The performance of detectors USAir and PSRTV was lower than that of a non-DOI detector, and thus these designs are favorable when the manufacturing cost is more important than timing performance. The results demonstrate that the proposed DOI-encoding method is a promising candidate for PET scanners that require high resolution and sensitivity and operate with conventional acquisition systems.
View details for DOI 10.1088/1361-6560/aa5076
View details for Web of Science ID 000391707000002
View details for PubMedID 28000613
Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging
JOURNAL OF NUCLEAR MEDICINE
2016; 57 (8): 1309–15
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.A SiPM-based PET insert that has the peak sensitivity of 3.4% and center volumetric resolution of 1.92/0.53 mm(3) (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.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.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.
View details for DOI 10.2967/jnumed.115.170019
View details for Web of Science ID 000385263600031
View details for PubMedID 27081173
Evaluation of a silicon photomultiplier PET insert for simultaneous PET and MR imaging
2016; 43 (1): 72–83
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.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.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.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.
View details for DOI 10.1118/1.4937784
View details for Web of Science ID 000370850600060
View details for PubMedID 26745901
Continuous depth-of-interaction measurement in a single-layer pixelated crystal array using a single-ended readout
PHYSICS IN MEDICINE AND BIOLOGY
2013; 58 (5): 1269–82
We propose a depth-of-interaction (DOI)-encoding method to extract continuous DOI information using a single-layer scintillation crystal array with single-ended readout for cost-effective high-resolution positron emission tomography (PET). DOI information is estimated by different light dispersions along the x- and y-directions tailored by the geometric shape of reflectors around the crystals. The detector module comprised a 22 × 22 array of unpolished LGSO crystals (2.0 × 2.0 × 20 mm(3)). A multi-anode photomultiplier tube with 64 anodes measured light dispersion in the crystal array. Gain non-uniformity of each anode was corrected by an analogue gain compensation circuit. DOI information was determined from peaks in the x and y anode-signal distributions normalized by the total energy of the distribution. Average DOI resolution (full width at half maximum, FWHM) over all crystals and depths was estimated to be 4.2 mm. Average energy resolution from the 2 to 18 mm DOI positions was 11.3% ± 0.79%, with 13% difference in photo-peak positions. Average time resolutions (FWHM) were 320-356 ps. Energy, time and DOI resolutions were uniform over all crystal positions except at the array's edge. This DOI-PET detector shows promise for applications that require high resolution and sensitivity at low cost.
View details for DOI 10.1088/0031-9155/58/5/1269
View details for Web of Science ID 000315191400007
View details for PubMedID 23384966