To view publications of the individual lab members, check out the People section.

Professor of Radiology (Molecular Imaging Program at Stanford/Nuclear Medicine) and, by courtesy, of Physics, of Electrical Engineering and of Bioengineering


  • Toward "super-scintillation" with nanomaterials and nanophotonics. Nanophotonics Carr Delgado, H., Moradifar, P., Chinn, G., Levin, C. S., Dionne, J. A. 2024; 13 (11): 1953-1962


    Following the discovery of X-rays, scintillators are commonly used as high-energy radiation sensors in diagnostic medical imaging, high-energy physics, astrophysics, environmental radiation monitoring, and security inspections. Conventional scintillators face intrinsic limitations including a low extraction efficiency of scintillated light and a low emission rate, leading to efficiencies that are less than 10 % for commercial scintillators. Overcoming these limitations will require new materials including scintillating nanomaterials ("nanoscintillators"), as well as new photonic approaches that increase the efficiency of the scintillation process, increase the emission rate of materials, and control the directivity of the scintillated light. In this perspective, we describe emerging nanoscintillating materials and three nanophotonic platforms: (i) plasmonic nanoresonators, (ii) photonic crystals, and (iii) high-Q metasurfaces that could enable high performance scintillators. We further discuss how a combination of nanoscintillators and photonic structures can yield a "super scintillator" enabling ultimate spatio-temporal resolution while enabling a significant boost in the extracted scintillation emission.

    View details for DOI 10.1515/nanoph-2023-0946

    View details for PubMedID 38745841

    View details for PubMedCentralID PMC11090085

  • Toward "super-scintillation" with nanomaterials and nanophotonics NANOPHOTONICS Delgado, H., Moradifar, P., Chinn, G., Levin, C. S., Dionne, J. A. 2024
  • A Scalable Dynamic TOT Circuit for a 100 ps TOF-PET Detector Design to Improve Energy Linearity and Dynamic Range IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Pourashraf, S., Cates, J. W., Levin, C. S. 2024; 8 (3): 237-247
  • PET System Technology: Theoretical Aspects and Experimental Methodology. Methods in molecular biology (Clifton, N.J.) Gonzalez-Montoro, A., Levin, C. S. 2024; 2729: 343-369


    Positron emission tomography (PET) imaging provides unique information of the cellular and molecular pathways of disease occurring within the human body, using measurements made from outside the body, which has shown utility in a variety of studies from basic research to clinical applications. This chapter describes some of the most relevant PET system parameters that impact its imaging performance such as 3D spatial, energy, and coincidence timing resolutions and the methodology typically used to evaluate those parameters. In addition, the physical principles underlying PET imaging, PET photon detector technology, and coincidence detection are also described. As a closing remark, the future perspectives of PET imaging and its simultaneous use with anatomical imaging techniques (e.g., computed tomography [CT] and magnetic resonance imaging [MRI]) are outlined.

    View details for DOI 10.1007/978-1-0716-3499-8_20

    View details for PubMedID 38006506

  • Compact FPGA-Based Data Acquisition System for a High-Channel, High-Count-Rate TOF-PET Insert for Brain PET/MRI IEEE TRANSACTIONS ON INSTRUMENTATION AND MEASUREMENT Dong, Q., Sajedi, S., Cui, K., Levin, C. S. 2024; 73
  • MRI compatibility study of a prototype radiofrequency penetrable oval PET insert at 3 T. Japanese journal of radiology Akram, M. S., Nishikido, F., Levin, C. S., Takyu, S., Obata, T., Yamaya, T. 2023


    To perform an MRI compatibility study of an RF field-penetrable oval-shaped PET insert that implements an MRI built-in body RF coil both as a transmitter and a receiver.Twelve electrically floating RF shielded PET detector modules were used to construct the prototype oval PET insert with a major axis of 440 mm, a minor axis of 350 mm, and an axial length of 225 mm. The electric floating of the PET detector modules was accomplished by isolating the cable shield from the detector shield using plastic tape. Studies were conducted on the transmit (B1) RF field, the image signal-to-noise ratio (SNR), and the RF pulse amplitude for a homogeneous cylindrical (diameter: 160 mm and length: 260 mm) phantom (NaCl + NiSO4 solution) in a 3 T clinical MRI system (Verio, Siemens, Erlangen, Germany).The B1 maps for the oval insert were similar to the MRI-only field responses. Compared to the MRI-only values, SNR reductions of 51%, 45%, and 59% were seen, respectively, for the spin echo (SE), gradient echo (GE), and echo planar (EPI) images for the case of oval PET insert. Moreover, the required RF pulse amplitudes for the SE, GE, and EPI sequences were, respectively, 1.93, 1.85, and 1.36 times larger. However, a 30% reduction in the average RF reception sensitivity was observed for the oval insert.The prototype floating PET insert was a safety concern for the clinical MRI system, and this compatibility study provided clearance for developing a large body size floating PET insert for the existing MRI system. Because of the RF shield of the insert, relatively large RF powers compared to the MRI-only case were required. Because of this and also due to low RF sensitivity of the body coil, the SNRs reduced largely.

    View details for DOI 10.1007/s11604-023-01514-y

    View details for PubMedID 38110835

    View details for PubMedCentralID 4849712

  • A simulation of a high-resolution cadmium zinc telluride positron emission tomography system. Medical physics Stanford-Hill, R., Groll, A., Levin, C. S. 2023


    A CZT (cadmium zinc telluride) PET (positron emission tomography) system is being developed at Stanford University. CZT has the promise of outperforming scintillator-based systems in energy and spatial resolution but has relatively poor coincidence timing resolution.To supplement GATE (GEANT 4 Application for Emission Tomography) simulations with charge transport and electronics modeling for a high-resolution CZT PET system.A conventional GATE simulation was supplemented with electron-hole transport modeling and experimentally measured single detector energy resolution to improve the system-level understanding of a CZT high-resolution PET system in development at Stanford University. The modeling used GATE hits data and applied charge transport in the crystal and RC-CR processing of the simulated signals to model the electronics, including leading-edge discriminators and peak pick-off. Depth correction was also performed on the simulation data. Experimentally acquired data were used to determine energy resolution parameters and were compared to simulation data.The distributions of the coincidence timing, anode energy, and cathode energy are consistent with experimental data. Numerically, the simulation achieved 153 ns FWHM coincidence time resolution (CTR), which is of the same order of magnitude as the raw 210 ns CTR previously found experimentally. Further, the anode energy resolution was found to be 5.9% FWHM (full width at half maximum) at 511 keV in the simulation, which is between the experimental value found for a single crystal of 3% and the value found for the dual-panel setup of 8.02%, after depth correction.Developing this advanced simulation improves upon the limitations of GATE for modeling semiconductor PET systems and provides a means for deeper analysis of the coincidence timing resolution and other complementary electron-hole dependent system parameters.

    View details for DOI 10.1002/mp.16856

    View details for PubMedID 38100261

  • Simulation of ionization charge carrier cascade time and density for a new radiation detection method based on modulation of optical properties. Medical physics Jeong, D., Tao, L., Song, X. R., Adams, Z., Zhang, X., Wang, J., Levin, C. S. 2023


    In time-of-flight PET, image quality and accuracy can be enhanced by improving the annihilation photon pair coincidence time resolution, which is the variation in the arrival time difference between the two annihilation photons emitted from each positron decay in the patient. Recent studies suggest direct detection of ionization tracks and their resulting modulation of optical properties, instead of scintillation, can improve the CTR significantly, potentially down to less than 10 ps CTR. However, the arrival times of the 511 keV photons are not predictable, leading to challenges in the spatiotemporal localization characterization of the induced charge carriers in the detector crystal.To establish an optimized experimental setup for measuring ionization induced modulation of optical properties, it is critical to develop a versatile simulation algorithm that can handle multiple detector material properties and time-resolved charge carrier dynamics.We expanded our previous algorithm and simulated ionization tracks, cascade time and induced charge carrier density over time in different materials. For designing a proof-of-concept experiment, we simulated ultrafast electrons and free-electron x-ray photons for timing characterization along with alpha and beta particles for higher spatial localization.With 3 MeV ultrafast electrons, by reducing detector crystal thickness, we can effectively reduce the ionization cascade time to 0.79 ps and deposited energy to 198.5 keV, which is on the order of the desired 511 keV energy. Alpha source simulations produced a cascade time of 2.45 ps and charge carrier density of 6.39 × 1020 cm-3 . Compared to the previous results obtained from 511 keV photon-induced ionization track simulations, the cascade time displayed similar characteristics, while the charge density was found to be higher. These findings suggest that alpha sources have the potential to generate a stronger ionization-induced signal using the modulation of optical properties as the detection mechanism.This work provides a guideline to understand, design and optimize an experimental platform that is highly sensitive and temporally precise enough to detect single 511 keV photon interactions with a goal to advance CTR for ToF-PET.

    View details for DOI 10.1002/mp.16855

    View details for PubMedID 38064645

  • Design and Characterization of the Detector Readout Electronics Used in PET<i>coil</i>: an RF-Penetrable TOF-PET Insert for PET/MRI IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Dong, Q., Sacco, I., Chang, C., Levin, C. S. 2023; 7 (8): 819-829
  • Study on the radiofrequency transparency of partial-ring oval-shaped prototype PET inserts in a 3 T clinical MRI system. Radiological physics and technology Akram, M. S., Levin, C. S., Nishikido, F., Takyu, S., Obata, T., Yamaya, T. 2023


    The purpose of this study is to evaluate the RF field responses of partial-ring RF-shielded oval-shaped positron emission tomography (PET) inserts that are used in combination with an MRI body RF coil. Partial-ring PET insert is particularly suitable for interventional investigation (e.g., trimodal PET/MRI/ultrasound imaging) and intraoperative (e.g., robotic surgery) PET/MRI studies. In this study, we used electrically floating Faraday RF shield cages to construct different partial-ring configurations of oval and cylindrical PET inserts and performed experiments on the RF field, spin echo and gradient echo images for a homogeneous phantom in a 3 T clinical MRI system. For each geometry, partial-ring configurations were studied by removing an opposing pair or a single shield cage from different positions of the PET ring. Compared to the MRI-only case, reduction in mean RF homogeneity, flip angle, and SNR for the detector opening in the first and third quadrants was approximately 13%, 15%, and 43%, respectively, whereas the values were 8%, 23%, and 48%, respectively, for the detector openings in the second and fourth quadrants. The RF field distribution also varied for different partial-ring configurations. It can be concluded that the field penetration was high for the detector openings in the first and third quadrants of both the inserts.

    View details for DOI 10.1007/s12194-023-00747-w

    View details for PubMedID 37874462

    View details for PubMedCentralID 4463332

  • Sparse SiPM Pixel Arrangement for a TOF-PET Detector Design that Achieves 100 ps Coincidence Time Resolution IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Cates, J. W., Levin, C. S. 2023; 7 (7): 665-672
  • Investigation of Faraday cage materials with low eddy current and high RF shielding effectiveness for PET/MRI applications. Physics in medicine and biology Dong, Q., Adams, Z., Watkins, R. D., Chang, C. M., Lee, B. J., Levin, C. S. 2023


    This study aims to evaluate radiofrequency (RF) shielding effectiveness (SE), gradient-induced eddy current, MR susceptibility, and PET photon attenuation of six shielding materials: copper plate, copper tape, carbon fiber fabric, stainless steel mesh, phosphor bronze mesh, and a spray-on conductive coating. Approach. We evaluated the six shielding materials by implementing them on identical clear plastic enclosures. We measured the RF SE and eddy current in benchtop experiments (outside of the MR environment) and in a 3T MR scanner. The magnetic susceptibility performance was evaluated in the same MR scanner. Additionally, we measured their effects on PET detectors, including global coincidence time resolution, global energy resolution, and coincidence count rate. Main results. The RF SEs for copper plate, copper tape, carbon fiber fabric, stainless steel mesh, phosphor bronze mesh, and conductive coating enclosures were 56.8±5.8, 63.9±4.3, 33.1±11.7, 43.6±4.5, 52.7±4.6, and 47.8±7.1 dB, respectively, in the benchtop experiment. Copper plate and copper tape experienced the most eddy current at 10 kHz in the benchtop experiment and also generated the largest ghosting artifacts in the MR scanner. Stainless steel mesh had the highest mean absolute difference (7.6±0.2 Hz) compared to the reference in the MR susceptibility evaluation. The carbon fiber fabric and phosphor bronze mesh enclosures caused the largest photon attenuation, reducing the coincidence count rate by 3.3 %, while the rest caused less than 2.6 %. Significance. The conductive coating proposed in this study is shown to be a high-performance Faraday cage material for PET/MRI applications based on its overall performance in all the experiments conducted in this study, as well as its ease and flexibility of manufacturing. As a result, it will be selected as the Faraday cage material for our second-generation MR-compatible PET insert.

    View details for DOI 10.1088/1361-6560/acdec4

    View details for PubMedID 37321248

  • The PETcoil project: PET performance evaluation of two detector modules for a second generation RF-penetrable TOF-PET brain dedicated insert for simultaneous PET/MRI. Physics in medicine and biology Dong, Q., Chang, C., Lee, B. J., Sacco, I., Sajedi, S., Adams, Z., Fischer, P., Levin, C. S. 2023


    OBJECTIVE: We are developing a portable, "RF-penetrable", brain-dedicated time of flight (TOF)-PET insert (PETcoil) for simultaneous PET/MRI.APPROACH: In this paper, we evaluate the PET performance of two fully assembled detector modules for this insert design outside the MR room.MAIN RESULTS: The global coincidence time resolution, global 511 keV energy resolution, coincidence count rate, and detector temperature achieved over 2-hour data collection were 242.2 ± 0.4 ps FWHM, 11.19 ± 0.02% FWHM, 22.0 ± 0.1 kcps, and 23.5 ± 0.3 °C, respectively. The intrinsic spatial resolutions in the axial and transaxial directions were 2.74 ± 0.01 mm FWHM and 2.88 ± 0.03 mm FWHM, respectively.SIGNIFICANCE: These results demonstrate excellent TOF capability and the performance and stability necessary for scaling up to a full ring comprising 16 detector modules.

    View details for DOI 10.1088/1361-6560/acc3f2

    View details for PubMedID 36913739

  • Study of compatibility between a 3T MR system and detector modules for a second generation RF-penetrable TOF-PET insert for simultaneous PET/MRI. Medical physics Dong, Q., Adams, Z., Watkins, R. D., Lee, B. J., Chang, C. M., Sacco, I., Levin, C. S. 2023


    Simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) has shown promise in acquiring complementary multiparametric information of disease. However, designing these hybrid imaging systems is challenging due to the propensity for mutual interference between the PET and MRI sub-systems. Currently, there are integrated PET/MRI systems for clinical applications. For neurologic imaging, a brain-dedicated PET insert provides superior spatial resolution and sensitivity compared to body PET scanners.Our first-generation prototype brain PET insert ("PETcoil") demonstrated RF-penetrability and MR-compatibility. In the second-generation PETcoil system, all analog silicon photomultiplier (SiPM) signal digitization is moved inside the detectors, which results in substantially better PET detector performance, but presents a greater technical challenge for achieving MR-compatibility. In this paper, we report results from MR-compatibility studies of two fully assembled second-generation PET insert detector modules.We studied the effect of the presence of the two second-generation TOF-PET insert detectors on parameters that affect MR image quality and evaluated TOF-PET detector performance under different MRI pulse sequence conditions.With the presence of operating PET detectors, no RF noise peaks were induced in the MR images, but the relative average noise level was increased by 15%, which led to a 3.1 dB to 4.2 dB degradation in MR image signal-to-noise ratio (SNR). The relative homogeneity of MR images degraded by less than 1.5% with the two operating TOF-PET detectors present. The reported results also indicated that ghosting artifacts (percent signal ghosting (PSG) ⩽ 1%) and MR susceptibility artifacts (0.044 ppm) were insignificant. The PET detector data showed a relative change of less than 5% in detector module performance between running outside and within the MR bore under different MRI pulse sequences except for energy resolution in EPI sequence (13% relative difference).The PET detector operation did not cause any significant artifacts in MR images and the performance and TOF capability of the former were preserved under different tested MR conditions.

    View details for DOI 10.1002/mp.16354

    View details for PubMedID 36912373

  • Design considerations for PET detectors with 100 picoseconds coincidence time resolution NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT Gonzalez-Montoro, A., Pourashraf, S., Lee, M. S., Cates, J. W., Levin, C. S. 2023; 1045
  • Predicting final ischemic stroke lesions from initial diffusion-weighted images using a deep neural network. NeuroImage. Clinical Nazari-Farsani, S., Yu, Y., Armindo, R. D., Lansberg, M., Liebeskind, D. S., Albers, G., Christensen, S., Levin, C. S., Zaharchuk, G. 2022; 37: 103278


    For prognosis of stroke, measurement of the diffusion-perfusion mismatch is a common practice for estimating tissue at risk of infarction in the absence of timely reperfusion. However, perfusion-weighted imaging (PWI) adds time and expense to the acute stroke imaging workup. We explored whether a deep convolutional neural network (DCNN) model trained with diffusion-weighted imaging obtained at admission could predict final infarct volume and location in acute stroke patients.In 445 patients, we trained and validated an attention-gated (AG) DCNN to predict final infarcts as delineated on follow-up studies obtained 3 to 7 days after stroke. The input channels consisted of MR diffusion-weighted imaging (DWI), apparent diffusion coefficients (ADC) maps, and thresholded ADC maps with values less than 620 × 10-6 mm2/s, while the output was a voxel-by-voxel probability map of tissue infarction. We evaluated performance of the model using the area under the receiver-operator characteristic curve (AUC), the Dice similarity coefficient (DSC), absolute lesion volume error, and the concordance correlation coefficient (ρc) of the predicted and true infarct volumes.The model obtained a median AUC of 0.91 (IQR: 0.84-0.96). After thresholding at an infarction probability of 0.5, the median sensitivity and specificity were 0.60 (IQR: 0.16-0.84) and 0.97 (IQR: 0.93-0.99), respectively, while the median DSC and absolute volume error were 0.50 (IQR: 0.17-0.66) and 27 ml (IQR: 7-60 ml), respectively. The model's predicted lesion volumes showed high correlation with ground truth volumes (ρc = 0.73, p < 0.01).An AG-DCNN using diffusion information alone upon admission was able to predict infarct volumes at 3-7 days after stroke onset with comparable accuracy to models that consider both DWI and PWI. This may enable treatment decisions to be made with shorter stroke imaging protocols.

    View details for DOI 10.1016/j.nicl.2022.103278

    View details for PubMedID 36481696

  • Study of Annihilation Photon Pair Coincidence Time Resolution Using Prompt Photon Emissions in New Perovskite Bulk Crystals IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Tao, L., He, Y., Kanatzidis, M. G., Levin, C. S. 2022; 6 (7): 804-810
  • Study of Annihilation Photon Pair Coincidence Time Resolution Using Prompt Photon Emissions in New Perovskite Bulk Crystals. IEEE transactions on radiation and plasma medical sciences Tao, L., He, Y., Kanatzidis, M. G., Levin, C. S. 2022; 6 (7): 804-810


    Semiconductor-based radiation detectors can typically achieve better energy and spatial resolution when compared to scintillator-based detectors. However, if used for positron emission tomography (PET), semiconductor-based detectors normally cannot achieve excellent coincidence time resolution (CTR), due to the relatively slow charge carrier collection time limited by the carrier drift velocity. If we can collect prompt photons emitted from certain semiconductor materials, there are possibilities that the CTR can be greatly improved, and time-of-flight (ToF) capability can be achieved. In this paper, we studied the prompt photon emission (mainly Cherenkov luminescence) property and fast timing capability of cesium lead chloride (CsPbCl3) and cesium lead bromide (CsPbBr3), which are two new perovskite semiconductor materials. We also compared their performance with thallium bromide (TlBr), another semiconductor material that has already been studied for timing using its Cherenkov emissions. We performed coincidence measurements using silicon photomultipliers (SiPMs), and the full-width-at-half-maximum (FWHM) CTR acquired between a semiconductor sample crystal and a reference lutetium-yttrium oxyorthosilicate (LYSO) crystal (both with dimensions of 3 × 3 × 3 mm3) is 248 ± 8 ps for CsPbCl3, 440 ± 31 ps for CsPbBr3, and 343 ± 16 ps for TlBr. Deconvolving the contribution to CTR from the reference LYSO crystal (around 100 ps) and then multiplying by the square root of 2, the estimated CTR between two of the same semiconductor crystals was calculated as 324 ± 10 ps for CsPbCl3, 606 ± 43 ps for CsPbBr3 and 464 ± 22 ps for TlBr. This ToF capable CTR performance combined with an easily scalable crystal growth process, low cost and toxicity, as well as good energy resolution lead us to the conclusion that new perovskite materials such as CsPbCl3 and CsPbBr3 could be excellent candidates as PET detector materials.

    View details for DOI 10.1109/trpms.2022.3149992

    View details for PubMedID 37008042

    View details for PubMedCentralID PMC10065467

  • Advances in Detector Instrumentation for PET. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Gonzalez-Montoro, A., Ullah, M. N., Levin, C. S. 2022; 63 (8): 1138-1144


    During the last 3 decades, PET has become a standard-of-care imaging technique used in the management of cancer and in the characterization of neurologic disorders and cardiovascular disease. It has also emerged as a prominent molecular imaging method to study the basic biologic pathways of disease in rodent models. This review describes the basics of PET detectors, including a detailed description of indirect and direct 511-keV photon detection methods. We will also cover key detector performance parameters and describe detector instrumentation advances during the last decade.

    View details for DOI 10.2967/jnumed.121.262509

    View details for PubMedID 35914819

  • Investigation of Electronic Signal Processing Chains for a Prototype TOF-PET System With 100-ps Coincidence Time Resolution. IEEE transactions on radiation and plasma medical sciences Pourashraf, S., Gonzalez-Montoro, A., Lee, M. S., Cates, J. W., Won, J. Y., Lee, J. S., Levin, C. S. 2022; 6 (6): 690-696


    We have evaluated CTR performance of four different mixed-signal front-end electronic readout configurations with the goal to achieve 100 picoseconds (ps) coincidence time resolution (CTR). The proposed TOF-PET detector elements are based on two 3 × 3 × 10 mm3 "fast LGSO" crystal segments, side-coupled to linear arrays of 3 × 3 mm2 silicon photomultipliers (SiPMs), to form a total crystal length of 20 mm. We studied multiple configurations and components for the front-end readout: 1) high speed radio frequency (RF) amplifiers; 2) an ASIC-based discriminator; 3) combination of RF amplifier, balun transformer, and discriminator ASIC; and 4) combination of balun transformer, and discriminator ASIC. Using two 3 × 3 × 10 mm3 fast LGSO crystals side coupled to a linear array of three SiPMs, coincidence data were experimentally acquired for each readout configuration in combination with a low jitter field programmable gate array (FPGA)-based time to digital converter (TDC). After evaluating timing performance of the three readout schemes, the best CTR value of 99.4 ± 1.9 ps FWHM was achieved for configuration (3), which is more than 20 ps better than the results achieved using configurations (1) and (2).

    View details for DOI 10.1109/trpms.2021.3124756

    View details for PubMedID 36060422

    View details for PubMedCentralID PMC9432859

  • Cherenkov Radiation-Based Coincidence Time Resolution Measurements in BGO Scintillators FRONTIERS IN PHYSICS Gonzalez-Montoro, A., Pourashraf, S., Cates, J. W., Levin, C. S. 2022; 10
  • Investigation of Electronic Signal Processing Chains for a Prototype TOF-PET System with 100 ps Coincidence Time Resolution IEEE Transactions on Radiation and Plasma Medical Sciences Pourashraf, S., Gonzalez-Montoro, A., Lee, M., Cates, J. W., Won, J. Y., Lee, J. S., Levin, C. S. 2022; 6 (6): 690 - 696
  • Application of Artificial Intelligence in PET Instrumentation. PET clinics Ullah, M. N., Levin, C. S. 2022; 17 (1): 175-182


    Artificial intelligence (AI) has been widely used throughout medical imaging, including PET, for data correction, image reconstruction, and image processing tasks. However, there are number of opportunities for the application of AI in photon detector performance or the data collection process, such as to improve detector spatial resolution, time-of-flight information, or other PET system performance characteristics. This review outlines current topics, research highlights, and future directions of AI in PET instrumentation.

    View details for DOI 10.1016/j.cpet.2021.09.011

    View details for PubMedID 34809865

  • Study of optical reflectors for a 100ps coincidence time resolution TOF-PET detector design. Biomedical physics & engineering express Gonzalez-Montoro, A., Pourashraf, S., Lee, M. S., Cates, J. W., Levin, C. S. 2021


    Positron Emission Tomography (PET) reconstructed image signal-to-noise ratio (SNR) can be improved by including the 511 keV photon pair coincidence time-of-flight (TOF) information. The degree of SNR improvement from this TOF capability depends on the coincidence time resolution (CTR) of the PET system, which is essentially the variation in photon arrival time differences over all coincident photon pairs detected for a point positron source placed at the system center. The CTR is determined by several factors including the intrinsic properties of the scintillation crystals and photodetectors, crystal-to-photodetector coupling configurations, reflective materials, and the electronic readout configuration scheme. The goal of the present work is to build a novel TOF-PET system with 100 picoseconds (ps) CTR, which provides an additional factor of 1.5-2.0 improvement in reconstructed image SNR compared to state-of-the-art TOF-PET systems which achieve 225 - 400 ps CTR. A critical parameter to understand is the optical reflector's influence on scintillation light collection and transit time variations to the photodetector. To study the effects of the reflector covering the scintillation crystal element on CTR, we have tested the performance of four different reflector materials: Enhanced Specular Reflector (ESR) -coupled with air or optical grease to the scintillator; Teflon tape; BaSO4 paint alone or mixed with epoxy; and TiO2 paint. For the experimental set-up, we made use of 3*3*10 mm3 fast-LGSO:Ce scintillation crystal elements coupled to an array of silicon photomultipliers (SiPMs) using a novel "side-readout" configuration that has proven to have lower variations in scintillation light collection efficiency and transit time to the photodetector. Results show CTR values of 102.0±0.8, 100.2±1.2, 97.3±1.8 and 95.0±1.0 ps full-width-half-maximum (FWHM) with non-calibrated energy resolutions of 10.2±1.8, 9.9±1.2, 7.9±1.2, and 8.6±1.7 % FWHM for the Teflon, ESR (without grease), BaSO4 (without epoxy) and TiO2 paint treatments, respectively.

    View details for DOI 10.1088/2057-1976/ac240e

    View details for PubMedID 34488203

  • Reduced Acquisition Time Per Bed Position for PET/MRI Using 68Ga-RM2 or 68Ga-PSMA11 in Patients With Prostate Cancer: A Retrospective Analysis. AJR. American journal of roentgenology Duan, H., Baratto, L., Hatami, N., Liang, T., Levin, C. S., Khalighi, M. M., Iagaru, A. 2021


    Background: Growing clinical adoption of PET/MRI for prostate cancer (PC) evaluation has increased interest in reducing PET/MRI scan times. Reducing acquisition time per bed position below current times of at least 5 minutes would allow shorter examination lengths. Objective: To evaluate the effect of different reduced PET acquisition times in patients with PC who underwent 68Ga-PSMA11 or 68Ga-RM2 PET/MRI using highly sensitive silicon photomultiplier-based PET detectors. Methods: This study involved retrospective review of men with PC who underwent PET/MRI as part of one of two prospective trials. Fifty men (mean age, 69.9±6.8 years) who underwent 68Ga-RM2 PET/MRI and 50 men (66.6±5.7 years) who underwent 68Ga-PSMA11 PET/MRI were included. PET/MRI used a time-of-flight-enabled system with silicon photomultiplier-based detectors. Acquisition time was 4 minutes per bed position. PET data were reconstructed using acquisition times of 30 seconds, 1 minute, 2 minutes, 3 minutes, and 4 minutes. Three readers independently assessed image quality for each reconstruction using 1-5 scale (1=non-diagnostic; 5=excellent quality). One reader measured SUVmax for up to 6 lesions per patient. Two readers independently assessed lesion conspicuity using 1-3 scale (1=not visualized; 3=definitely visualized). Results: Mean image quality across readers at 30 seconds, 1 minutes, 2 minutes, 3 minutes, and 4 minutes was, for 68Ga-RM2 PET/MRI, 1.0±0.2 to 1.7±0.7, 2.0±0.3 to 2.6±0.8, 3.1±0.5 to 3.9±0.8, 4.6±0.6 to 4.7±0.6, and 4.8±0.4 to 4.8±0.5, respectively, and for 68Ga-PSMA11 PET/MRI was 1.2±0.4 to 1.8±0.6, 2.2±0.4 to 2.8±0.7, 3.6±0.6 to 4.1±0.8, 4.8±0.4 to 4.9±0.4, and 4.9±0.3 to 5.0±0.2, respectively. Mean lesion SUVmax for 68Ga-RM2 PET/MRI was 11.1±12.4, 10.2±11.7, 9.6±11.3, 9.5±11.6, and 9.4±11.6, respectively, and for 68Ga-PSMA11 PET/MRI was 14.7±8.2, 12.9±7.4, 12.1±7.8, 11.7±7.9, and 11.6±7.9, respectively. Mean lesion conspicuity (reader 1/reader 2) was, for 68Ga-RM2 PET/MRI, 2.4±0.5/2.7±0.5, 2.9±0.3/2.9±0.3, 3.0±0.0/3.0±0.0, 3.0±0.0/3.0±0.0, and 3.0±0.0/3.0±0.0, respectively, and for 68Ga-PSMA11 PET/MRI was 2.6±0.5/2.8±0.4, 3.0±0.2/2.9±0.3, 3.0±0.1/3.0±0.2, 3.0±0.0/3.0±0.0, and 3.0±0.0/3.0±0.0, respectively. Conclusion: Our data support routine 3 minute acquisitions, which provided very similar results as 4 minute acquisitions. Two minute acquisition, though somewhat lowering quality, provided acceptable performance and warrants consideration. Clinical Impact: When evaluating PC using modern PET/MRI equipment, time per bed position may be reduced compared with historically used times.

    View details for DOI 10.2214/AJR.21.25961

    View details for PubMedID 34406051

  • High-resolution time-of-flight PET detector with 100 ps coincidence time resolution using a side-coupled phoswich configuration. Physics in medicine and biology Lee, M. S., Cates, J. W., Gonzalez-Montoro, A., Levin, C. S. 2021; 66 (12)


    Photon time-of-flight (TOF) capability in positron emission tomography (PET) enables reconstructed image signal-to-noise ratio (SNR) improvement. With the coincidence time resolution (CTR) of 100 picosecond (ps), a five-fold SNR improvement can be achieved with a 40 cm diameter imaging subject, relative to a system without TOF capability. This 100 ps CTR can be achieved for aclinically relevantdetector design (crystal element length ≥20 mm with reasonably high crystal packing fraction) using a side-readout PET detector configuration that enables 511 keV photon interaction depth-independent light collection efficiency and lower variance in scintillation photon transit time to the silicon photomultiplier (SiPM). In this study, we propose a new concept of TOF-PET detector to achieve high (<2 mm) resolution, using a 'side-coupled phoswich' configuration, where two crystals with different decay times (taud) are coupled in a side-readout configuration to a common row of photosensors. The proposed design was validated and optimized with GATE Monte Carlo simulation studies to determine an efficient detector design. Based on the simulation results, a proof-of-concept side-coupled phoswich detector design was developed comprising two LSO crystals with the size of 1.9*1.9*10 mm3with decay times of 34.39 and 43.07 ns, respectively. The phoswich crystals were side-coupled to the same three 4*4 mm2SiPMs and detector performances were evaluated. As a result of the experimental evaluation, the side-coupled phoswich configuration achieved CTR of 107±3 ps, energy resolution of 10.5%±1.21% at 511 keV and >95% accuracy in identifying interactions in the two adjacent 1.9*1.9*10 mm3crystal elements using the time-over-threshold technique. Based on our results, we can achieve excellent spatial and energy resolution in addition to 100 ps CTR with this novel detector design.

    View details for DOI 10.1088/1361-6560/ac01b5

    View details for PubMedID 34106089

  • New PET technologies - embracing progress and pushing the limits. European journal of nuclear medicine and molecular imaging Aide, N., Lasnon, C., Kesner, A., Levin, C. S., Buvat, I., Iagaru, A., Hermann, K., Badawi, R. D., Cherry, S. R., Bradley, K. M., McGowan, D. R. 2021

    View details for DOI 10.1007/s00259-021-05390-4

    View details for PubMedID 34081153

  • Results of a Prospective Trial to Compare 68Ga-DOTA-TATE with SiPM-Based PET/CT vs. Conventional PET/CT in Patients with Neuroendocrine Tumors. Diagnostics (Basel, Switzerland) Baratto, L., Toriihara, A., Hatami, N., Aparici, C. M., Davidzon, G., Levin, C. S., Iagaru, A. 2021; 11 (6)


    We prospectively enrolled patients with neuroendocrine tumors (NETs). They underwent a single 68Ga-DOTA-TATE injection followed by dual imaging and were randomly scanned using first either the conventional or the silicon photomultiplier (SiPM) positron emission tomography/computed tomography (PET/CT), followed by imaging using the other system. A total of 94 patients, 44 men and 50 women, between 35 and 91 years old (mean ± SD: 63 ± 11.2), were enrolled. Fifty-two out of ninety-four participants underwent SiPM PET/CT first and a total of 162 lesions were detected using both scanners. Forty-two out of ninety-four participants underwent conventional PET/CT first and a total of 108 lesions were detected using both scanners. Regardless of whether SiPM-based PET/CT was used first or second, maximum standardized uptake value (SUVmax) of lesions measured on SiPM was on average 20% higher when comparing two scanners with all enrolled patients, and the difference was statistically significant. SiPM-based PET/CT detected 19 more lesions in 13 patients compared with conventional PET/CT. No lesions were only identified by conventional PET/CT. In conclusion, we observed higher SUVmax for lesions measured from SiPM PET/CT compared with conventional PET/CT regardless of the order of the scans. SiPM PET/CT allowed for identification of more lesions than conventional PET/CT. While delayed imaging can lead to higher SUVmax in cancer lesions, in the series of lesions identified when SiPM PET/CT was used first, this was not the case; therefore, the data suggest superior performance of the SiPM PET/CT scanner in visualizing and quantifying lesions.

    View details for DOI 10.3390/diagnostics11060992

    View details for PubMedID 34070751

  • Evolution of PET Detectors and Event Positioning Algorithms Using Monolithic Scintillation Crystals IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Gonzalez-Montoro, A., Gonzalez, A. J., Pourashraf, S., Miyaoka, R. S., Bruyndonckx, P., Chinn, G., Pierce, L. A., Levin, C. S. 2021; 5 (3): 282-305
  • Pseudo CT Image Synthesis and Bone Segmentation From MR Images Using Adversarial Networks With Residual Blocks for MR-Based Attenuation Correction of Brain PET Data IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Tao, L., Fisher, J., Anaya, E., Li, X., Levin, C. S. 2021; 5 (2): 193–201
  • Further investigations of a radiation detector based on ionization-induced modulation of optical polarization. Physics in medicine and biology Wang, Y., Tao, L., Abbaszadeh, S., Levin, C. S. 2021


    Optical property modulation induced by ionizing radiation is a promising approach for ultra-fast, lower time jitter detection of photon arrival time. If successful, this method can be utilized in time-of-flight (TOF) positron emission tomography (PET) to achieve a coincidence time resolution (CTR) approaching 10 ps. In this work, the optical property modulation based method is further developed with focus on a detection setup based on two crossed polarizers. Previous work demonstrated that such an optical setup could be utilized in radiation detection, though its detection sensitivity needed improvement. This work investigates the angle between polarizers and electric eld distribution within the detection crystal to understand and improve the detection sensitivity of an optical polarization modulation based method. For this work, Cadmium Telluride (CdTe) was studied as the detector crystal. The "magic" angle (i.e. optimal working angle) of the two crossed polarizers based optical setup with CdTe was explored theoretically and experimentally. The experimental results show that the detection sensitivity could be improved by around 10% by determining the appropriate "magic" angle. We then studied the dependence of detection sensitivity on electric eld distribution as well as on the bias voltage across the detector crystal using CdTe crystals. The experimental results show that a smaller electrode on the detector crystal, or a more concentrated electric eld distribution could improve detection sensitivity. For CdTe, a detector crystal sample with 2.5 mm*2.5 mm square electrode has twice the detection sensitivity of a detector crystal with 5 mm*5 mm square electrode. Increasing the bias voltage before saturation for CdTe could further enhance the modulation strength and thus, the sensitivity. Our investigations demonstrated that by determining the proper working angle of polarizers and bias electrical distribution to the detector, we could improve the sensitivity of the proposed optical setup.

    View details for DOI 10.1088/1361-6560/abe027

    View details for PubMedID 33498027

  • Noninvasive and Highly Multiplexed Five-Color Tumor Imaging of Multicore Near-Infrared Resonant Surface-Enhanced Raman Nanoparticles In Vivo. ACS nano Yu, J. H., Steinberg, I., Davis, R. M., Malkovskiy, A. V., Zlitni, A., Radzyminski, R. K., Jung, K. O., Chung, D. T., Curet, L. D., D'Souza, A. L., Chang, E., Rosenberg, J., Campbell, J., Frostig, H., Park, S. M., Pratx, G., Levin, C., Gambhir, S. S. 2021


    In vivo multiplexed imaging aims for noninvasive monitoring of tumors with multiple channels without excision of the tissue. While most of the preclinical imaging has provided a number of multiplexing channels up to three, Raman imaging with surface-enhanced Raman scattering (SERS) nanoparticles was suggested to offer higher multiplexing capability originating from their narrow spectral width. However, in vivo multiplexed SERS imaging is still in its infancy for multichannel visualization of tumors, which require both sufficient multiplicity and high sensitivity concurrently. Here we create multispectral palettes of gold multicore-near-infrared (NIR) resonant Raman dyes-silica shell SERS (NIR-SERRS) nanoparticle oligomers and demonstrate noninvasive and five-plex SERS imaging of the nanoparticle accumulation in tumors of living mice. We perform the five-plex ratiometric imaging of tumors by varying the administered ratio of the nanoparticles, which simulates the detection of multiple biomarkers with different expression levels in the tumor environment. Furthermore, since this method does not require the excision of tumor tissues at the imaging condition, we perform noninvasive and longitudinal imaging of the five-color nanoparticles in the tumors, which is not feasible with current ex vivo multiplexed tissue analysis platforms. Our work surpasses the multiplicity limit of previous preclinical tumor imaging methods while keeping enough sensitivity for tumor-targeted in vivo imaging and could enable the noninvasive assessment of multiple biological targets within the tumor microenvironment in living subjects.

    View details for DOI 10.1021/acsnano.1c07470

    View details for PubMedID 34797988

  • Scalable electronic readout design for a 100 ps coincidence time resolution TOF-PET system. Physics in medicine and biology Pourashraf, S. n., Gonzalez-Montoro, A. n., Won, J. Y., Lee, M. S., Cates, J. W., Zhao, Z. n., Lee, J. S., Levin, C. S. 2021


    We have developed a scalable detector readout design for a 100 ps coincidence time resolution (CTR) time of flight (TOF) positron emission tomography (PET) detector technology. The basic scintillation detectors studied in this paper are based on 2×4 arrays of 3×3×10 mm³ "fast- LGSO:Ce" scintillation crystals side- coupled to 6×4 arrays of 3×3 mm² silicon photomultipliers (SiPMs). We employed a novel mixed-signal front-end electronic configuration and a low timing jitter Field Programming Gate Array (FPGA)-based time to digital converter (TDC) for data acquisition. Using a 22 Na point source, >10,000 coincidence events were experimentally acquired for several SiPM bias voltages, leading edge time-pickoff thresholds, and timing channels. CTR of 102.03 ± 1.9 ps full-width-at-half-maximum (FWHM) was achieved using single 3×3×10 mm³ "fast- LGSO" crystal elements, wrapped in Teflon tape and side coupled to a linear array of 3 SiPMs. In addition, the measured average CTR was 113.4 ± 0.7 ps for the side- coupled 2×4 crystal array. The readout architecture presented in this work is designed to be scalable to large area module detectors with a goal to create the first TOF-PET system with 100 ps FWHM CTR.

    View details for DOI 10.1088/1361-6560/abf1bc

    View details for PubMedID 33761476

  • Simulation studies to understand sensitivity and timing characteristics of an optical property modulation-based radiation detection concept for PET. Physics in medicine and biology Tao, L., Jeong, D., Wang, J., Adams, Z., Bryan, P., Levin, C. S. 2020


    The concept of using the modulation mechanisms of a material's optical properties for annihilation photon detection has been proposed as a potential method to significantly improve the coincidence time resolution (CTR) of positron emission tomography (PET) detectors. However, the possibility of detecting individual 511 keV photons with largely improved CTR using the proposed detection method has not yet been demonstrated, either experimentally or theoretically. In addition, the underlying physical picture of the optical modulation effects induced by annihilation photons has not been fully understood. In this work, we perform simulation studies including generation of the annihilation photon-induced ionization energy deposition trajectory, estimation of the charge carrier cascade time and temporal variance, simulation of the distribution of ionization-induced charge carrier density, and calculation of the strength of the modulation of two optical parameters: the absorption coefficient and the refractive index, as well as evaluation of the resulting optical intensity and phase change experienced by a probe laser beam. Our simulation results show that the average absorption coefficient modulation induced by individual 511 keV photon interactions is around 0.04/cm, and the average refractive index change is 3.6 * 10-5, leading to modulations in the probe laser intensity of around 0.1% and phase modulation of around 0.05 radians. We have also found that the ionization process induced by a single 511 keV photon interaction occurs within 2.3 ps with a temporal variance of 0.4 ps. The fundamental limit on CTR using the optical property modulation-based detection mechanism is estimated to be around 1.2 ps full width at half maximum (FWHM). Our simulation results indicate that with proper experiment design, it is possible to detect the ionization produced by an individual 511 keV photon with significantly improved CTR using the optical property modulation-based detection concept.

    View details for DOI 10.1088/1361-6560/aba938

    View details for PubMedID 32707569

  • Deep learning based methods for gamma ray interaction location estimation in monolithic scintillation crystal detectors. Physics in medicine and biology Tao, L., Li, X., Furenlid, L. R., Levin, C. S. 2020


    In this work, we explore deep learning based techniques using the information from mean detector response functions as a new method to estimate gamma ray interaction location in monolithic scintillation crystal detectors. Compared with searching based methods, deep learning techniques do not require recording all the MDRF information once the prediction networks are trained, which means the memory cost could be significantly reduced. In addition, the event positioning process using deep learning techniques only requires running through the network once, without the need to do searching in the reference dataset. This could greatly speed up the positioning process for each event. We have designed and trained four different neural networks to estimate the gamma ray interaction location given the MDRF data. We have studied network structures consisting only of fully connected (FC) layers, as well as convolutional neural networks (CNNs). In addition, we tried to use both regression and classification to generate the final prediction of the gamma ray interaction position. We evaluated the estimation accuracy, testing speed and memory cost (numbers of parameters) of different network architectures, and also compared them with the exhaustive search method. Our results indicate that deep learning based estimation methods with a well designed network structure can achieve a relative positioning error with respect to the ground truth determined by the exhaustive search method of below 1mm in both x and y directions (depth information is not considered in this work), which would imply a very high performance positioning algorithm for practical monolithic scintillation crystal detectors. The deep learning network also achieves a testing speed that is more than 400 times faster than the exhaustive search method. With proper design of the network structure, the deep learning based positioning methods have the potential to save memory cost by a factor of up to 100.

    View details for DOI 10.1088/1361-6560/ab857a

    View details for PubMedID 32235062