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


  • 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

  • Robust Detector Calibration for a Novel PET System Based on Cross-Strip CZT Detectors IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Vernekohl, D., Abbaszadeh, S., Gu, Y., Levin, C. S. 2019; 3 (6): 626–33
  • Fast gamma-ray interaction-position estimation using k-d tree search PHYSICS IN MEDICINE AND BIOLOGY Li, X., Tao, L., Levin, C. S., Furenlid, L. R. 2019; 64 (15)
  • Electronics method to advance the coincidence time resolution with bismuth germanate. Physics in medicine and biology Cates, J. W., Levin, C. S. 2019


    Exploiting the moderate Cherenkov yield from 511 keV photoelectric interactions in bismuth germanate (BGO) scintillators enables one to achieve a level of coincidence time resolution (CTR) appropriate for time-of-flight positron emission tomography (TOF-PET). For this approach, owing to the low number of promptly emitted light photons, single photon time resolution (SPTR) can have a stronger influence on achievable CTR. We have previously shown readout techniques that reduce effective device capacitance of large area silicon photomultipliers (SiPMs) can yield improvements in single photon response shape that minimize the influence of electronic noise on SPTR. With these techniques, sub-100 ps FWHM SPTR can be achieved with 4x4 mm&lt;sup&gt;2&lt;/sup&gt; FBK near-ultra-violet high density (NUV-HD) SiPMs. These sensors are also useful for detecting Cherenkov light due to relatively high photon detection efficiency for UV light. In this work, we measured CTR for BGO crystals coupled to FBK NUV-HD SiPMs with a passive bootstrapping readout circuit that effectively reduces the SiPM device capacitance. A range of CTR values between 200±3 and 277±7 ps FWHM were measured for 3x3x3 and 3x3x15 mm&lt;sup&gt;3&lt;/sup&gt; crystals, respectively. This readout technique provides a relatively simple approach to achieve state-of-the-art CTR performance using BGO crystals for TOF-PET.

    View details for DOI 10.1088/1361-6560/ab31e3

    View details for PubMedID 31300623

  • Time Resolution Studies for a 1-mm Resolution Clinical PET System With a Charge Sharing Readout and Leading Edge Discrimination IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Hsu, D. C., Freese, D. L., Innes, D. R., Levin, C. S. 2019; 3 (3): 285–91
  • Intercrystal scatter studies for a 1 mm(3) resolution clinical PET system prototype PHYSICS IN MEDICINE AND BIOLOGY Hsu, D. C., Freese, D. L., Innes, D. R., Levin, C. S. 2019; 64 (9)
  • Intercrystal scatter studies for a 1 mm<sup>3</sup> resolution clinical PET system prototype. Physics in medicine and biology Hsu, D. F., Freese, D. L., Innes, D. R., Levin, C. S. 2019


    Positron emission tomography (PET) systems designed with multiplexed readout do not usually have the capability to resolve individual intercrystal scatter (ICS) interactions, leading to interaction mispositioning that degrades spatial resolution and contrast. A 3D position sensitive scintillation detector capable of individual ICS readout has been designed and incorporated into a 1 mm<sup>3</sup> resolution clinical PET system used for locoregional imaging. Incorporating ICS events increases photon sensitivity by 51.5% compared to using only photoelectric events. A Compton scatter angle error minimization algorithm is used to estimate the first ICS interaction location for accurate line-of-response pairing of coincident photons. An optimal scatter angle error threshold of 15 degrees is used to discard ICS events with a high mismatch between energy-derived and position-derived intercrystal scatter angles. Finally, positioning rather than rejecting ICS events boosts peak contrast to noise ratio by 8.1%, and allows for an equivalent dose reduction of 12% while maintaining equivalent image quality.

    View details for PubMedID 30893659

  • Fast gamma-ray interaction-position estimation using k-d tree search. Physics in medicine and biology Li, X., Tao, L., Levin, C. S., Furenlid, L. R. 2019


    We have developed a fast gamma-ray interaction-position estimation method using k-d tree search, which can be combined with various kinds of closeness metrics such as Euclidean distance, maximum-likelihood estimation, etc.. Compared with traditional search strategies, this method can achieve both speed and accuracy at the same time using the k-d tree data structure. The k-d tree search method has a time complexity of O(log2(N)), where N is the number of entries in the reference data set, which means large reference datasets can be used to efficiently estimate each event's interaction position. This method's accuracy was found to be equal to that of the exhaustive search method, yielding the highest achievable accuracy. Most importantly, this method has no restriction on the data structure of the reference dataset and can still work with complicated mean-detector-response functions (MDRFs), meaning that it is more robust than other popular methods such as contracting-grid search (CG) or vector-search (VS) methods that could yield locally optimal result instead of globally optimal result.

    View details for PubMedID 30844778

  • Performance evaluation of RF coils integrated with an RF-penetrable PET insert for simultaneous PET/MRI MAGNETIC RESONANCE IN MEDICINE Lee, B. J., Watkins, R. D., Lee, K., Chang, C., Levin, C. S. 2019; 81 (2): 1434–46

    View details for DOI 10.1002/mrm.27444

    View details for Web of Science ID 000462086300057

  • Geometry optimization of electrically floating PET inserts for improved RF penetration for a 3T MRI system MEDICAL PHYSICS Akram, M., Levin, C. S., Obata, T., Hirumi, G., Yamaya, T. 2018; 45 (10): 4627–41


    An electrically floating radio frequency (RF) shielded PET insert with individual PET detectors shielded by separate Faraday cages enables the MRI built-in body RF coil to be used at least as an RF transmitter, in which the RF field penetrates the imaging region inside the PET ring through the narrow gaps between the shielded PET detector modules. Because the shielded PET ring blocks more than 90% of the imaging region for the transmit field from the body RF coil, it is very challenging to obtain the required RF field inside a full-ring floating PET insert. In this study, experiments were performed on the dependence of RF penetrability on different geometric aspects of the shielded PET modules and PET rings to optimize the design parameters to obtain the required RF field inside the PET ring.We developed several prototype cylindrical full-ring PET inserts using completely enclosed empty RF shield boxes (considered as dummy PET modules). Considering the RF shield box, we conducted studies for different axial lengths (240 and 120 mm) and heights (30 and 45 mm) of the shield boxes. On the other hand, considering the PET ring geometry, we also performed studies on three different categories of PET rings: a long-ring insert (longer than the MRI phantom), a short-ring insert (shorter than the MRI phantom), and a two-ring insert that combined two short-rings. In each ring category, two different inter-shield box gaps (1 and 3 mm) were considered. In the case of the two-ring insert, three different ring-gaps (5, 10, and 20 mm) were studied. In total, 21 PET inserts were studied with an inner diameter (i.d.) of 210 mm. To study the effect of ring diameter, another long-ring insert was studied for the 270 mm i.d. Experiments were conducted for the transmit RF (B1 ) fields and signal-to-noise ratios of spin-echo and gradient-echo images using a homogeneous phantom in a 700 mm bore-diameter 3 T clinical MRI system. RF pulse amplitudes generated automatically by the MRI system were recorded for comparison.A PET insert with a 3 mm inter-box gap was found to perform the best, at a level which is acceptable for PET imaging. In the case of an insert of multiple short-rings instead of one long-ring insert, the 5 and 10 mm ring-gaps provided higher RF field penetration. Increasing the inter-box gap improved the RF field penetration, whereas a ring-gap that was too wide concentrated the field near the ring-gap region. Relatively reduced RF power was required for wider inter-box gap or ring-gap or larger shield box height. Moreover, the rectangular shield box outperformed the trapezoidal shield box. On the other hand, when we changed the inner or outer diameter of the PET ring by keeping the same transaxial width of the shield boxes, we did not see any noticeable variation.Our study results provide comprehensive guidance on the geometrical design aspects of RF-penetrable PET inserts for efficient RF penetration inside the PET ring. By choosing proper geometric design parameters, we could get the RF field that was similar to the MRI-only case.

    View details for PubMedID 30118140

  • Performance evaluation of RF coils integrated with an RF-penetrable PET insert for simultaneous PET/MRI. Magnetic resonance in medicine Lee, B. J., Watkins, R. D., Lee, K. S., Chang, C., Levin, C. S. 2018


    PURPOSE: An "RF-penetrable" PET insert that allows the MR body coil to be used for RF transmission was developed to make it easier for an existing MR center to achieve simultaneous PET/MRI. This study focuses on experiments and analyses to study PET/RF coil configurations for simultaneous PET/MR studies.METHODS: To investigate the appropriate RF coil design, a transmit/receive (TX/RX) birdcage coil and an RX-only phased-array coil (TX from body coil), both fitting inside the PET ring were built and characterized. For MR performance evaluation, B1 field uniformity and MR image SNR were calculated. PET photon attenuation due to each coil was studied by means of CT-based attenuation maps and reconstructed PET images.RESULTS: When using the RX-only phased-array coil (TX from body coil), compared with the TX/RX birdcage coil, the B1 field uniformity and the MR image (gradient echo and fast spin echo) SNR increased by 2.4±4.8%, 386.1±62.3%, and 205.0±56.5%, respectively. Although some components of the coil were distributed within the PET FOV, no significant PET photon attenuation was shown in the CT-based attenuation map and reconstructed PET images.CONCLUSION: RF coil configurations for an RF-penetrable PET insert for simultaneous PET/MRI were studied. The RX-only phased-array coil (TX from body coil) outperformed the TX/RX birdcage coil with improved MR performance as well as negligible PET photon attenuation.

    View details for PubMedID 30260501

  • MR Performance in the Presence of a Radio Frequency-Penetrable Positron Emission Tomography (PET) Insert for Simultaneous PET/MRI IEEE TRANSACTIONS ON MEDICAL IMAGING Lee, B. J., Grant, A. M., Chang, C., Watkins, R. D., Glover, G. H., Levin, C. S. 2018; 37 (9): 2060–69


    Despite the great promise of integrated positron emission tomography (PET)/magnetic resonance (MR) imaging to add molecular information to anatomical and functional MR, its potential impact in medicine is diminished by a very high cost, limiting its dissemination. An RF-penetrable PET ring that can be inserted into any existing MR system has been developed to address this issue. Employing optical signal transmission along with battery power enables the PET ring insert to electrically float with respect to the MR system. Then, inter-modular gaps of the PET ring allow the RF transmit field from the standard built-in body coil to penetrate into the PET fields-of-view (FOV) with some attenuation that can be compensated for. MR performance, including RF noise, magnetic susceptibility, RF penetrability through and

  • Performance Study of a Radio-Frequency Field-Penetrable PET Insert for Simultaneous PET/MRI IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES Chang, C., Lee, B. J., Grant, A. M., Groll, A. N., Levin, C. S. 2018; 2 (5): 422–31
  • Improved single photon time resolution for analog SiPMs with front end readout that reduces influence of electronic noise. Physics in medicine and biology Cates, J. W., Gundacker, S., Auffray, E., Lecoq, P., Levin, C. S. 2018


    A key step to improving the coincidence time resolution of positron emission tomography detectors that exploit populations of prompt photon emissions is improving the single photon time resolution (SPTR) of silicon photomultipliers (SiPMs). The influence of electronic noise has previously been identified as the dominant factor affecting SPTR for large area, analog SiPMs. In this work, we measure the achievable SPTR with front end electronic readout that minimizes the influence of electronic noise. With this new readout circuit, the SPTR measured for one FBK NUV single avalanche photodiode (SPAD) was also achieved with a 1x1 mm<sup>2</sup> FBK NUV SiPM. SPTR for large area devices was also significantly improved. The measured SPTRs for 3x3 mm<sup>2</sup> Hamamatsu and SensL SiPMs were ≤150 ps FWHM, and SPTR ≤100 ps FWHM was measured for 3x3 mm<sup>2</sup> and 4x4 mm<sup>2</sup> FBK NUV and NUV-HD SiPMs. We also explore additional factors affecting the achievable SPTR for large area, analog SiPMs when the contribution of electronic noise is minimized and pinpoint potential areas of improvement to further reduce the SPTR of large area sensors towards that achievable for a single SPAD.

    View details for PubMedID 30129562

  • Evaluation of a clinical TOF-PET detector design that achieves ≤100 ps coincidence time resolution. Physics in medicine and biology Cates, J. W., Levin, C. S. 2018


    Commercially available clinical positron emission tomography (PET) detectors employ scintillation crystals that are long (20 mm length) and narrow (4-5 mm width) optically coupled on their narrow end to a photosensor. The aspect ratio of this traditional crystal rod conguration and 511 keV photon attenuation properties yield signicant variances in scintillation light collection efficiency and transit time to the photodetector, due to variations in the 511 keV photon interaction depth in the crystal. These variances contribute significantly to coincidence time resolution degradation. If instead, crystals are coupled to a photosensor on their long side, near-complete light collection efficiency can be achieved, and scintillation photon transit time jitter is substantially reduced. In this work, we compare the achievable coincidence time resolution (CTR) of LGSO:Ce(0.025 mol%) crystals 3-20 mm in length when optically coupled to silicon photomultipliers (SiPMs) on either their short end or long side face. In this "side readout" conguration, a CTR of 102±2 ps FWHM was measured with 2.9x.2.9x20 mm<sup>3</sup> crystals coupled to rows of 3x3 mm<sup>2</sup> SensL-J SiPMs using leading edge time pickoff and a single timing channel. This is in contrast to a CTR of 137±3 ps FWHM when the same crystals were coupled to single 3x3 mm<sup>2</sup> SiPMs on their narrow ends. We further study the statistical limit on CTR using side readout via the Cramer-Rao lower bound (CRLB), with consideration given to ongoing work to further improve photosensor technologies and exploit fast phenomena to ultimately achieve 10 ps FWHM CTR. Potential design aspects of scalable front-end signal processing readout electronics using this side readout conguration are discussed. Altogether, we demonstrate that the side readout conguration offers an immediate solution for 100 ps CTR clinical PET detectors and mitigates factors prohibiting future efforts to achieve 10 ps FWHM CTR.

    View details for PubMedID 29762136

  • Gray: a ray tracing-based Monte Carlo simulator for PET PHYSICS IN MEDICINE AND BIOLOGY Freese, D. L., Olcott, P. D., Buss, S. R., Levin, C. S. 2018; 63 (10): 105019


    Monte Carlo simulation software plays a critical role in PET system design. Performing complex, repeated Monte Carlo simulations can be computationally prohibitive, as even a single simulation can require a large amount of time and a computing cluster to complete. Here we introduce Gray, a Monte Carlo simulation software for PET systems. Gray exploits ray tracing methods used in the computer graphics community to greatly accelerate simulations of PET systems with complex geometries. We demonstrate the implementation of models for positron range, annihilation acolinearity, photoelectric absorption, Compton scatter, and Rayleigh scatter. For validation, we simulate the GATE PET benchmark, and compare energy, distribution of hits, coincidences, and run time. We show a [Formula: see text] speedup using Gray, compared to GATE for the same simulation, while demonstrating nearly identical results. We additionally simulate the Siemens Biograph mCT system with both the NEMA NU-2 scatter phantom and sensitivity phantom. We estimate the total sensitivity within [Formula: see text]% when accounting for differences in peak NECR. We also estimate the peak NECR to be [Formula: see text] kcps, or within [Formula: see text]% of published experimental data. The activity concentration of the peak is also estimated within 1.3%.

    View details for PubMedID 29701603

  • Design and Performance of a 1 mm(3) Resolution Clinical PET System Comprising 3-D Position Sensitive Scintillation Detectors IEEE TRANSACTIONS ON MEDICAL IMAGING Hsu, D. C., Freese, D. L., Reynolds, P. D., Innes, D. R., Levin, C. S. 2018; 37 (4): 1058–66


    We are developing a 1-mm3 resolution, high-sensitivity positron emission tomography (PET) system for loco-regional cancer imaging. The completed system will comprise two cm detector panels and contain 4 608 position sensitive avalanche photodiodes (PSAPDs) coupled to arrays of mm3 LYSO crystal elements for a total of 294 912 crystal elements. For the first time, this paper summarizes the design and reports the performance of a significant portion of the final clinical PET system, comprising 1 536 PSAPDs, 98 304 crystal elements, and an active field-of-view (FOV) of cm. The sub-system performance parameters, such as energy, time, and spatial resolutions are predictive of the performance of the final system due to the modular design. Analysis of the multiplexed crystal flood histograms shows 84% of the crystal elements have>99% crystal identification accuracy. The 511 keV photopeak energy resolution was 11.34±0.06% full-width half maximum (FWHM), and coincidence timing resolution was 13.92 ± 0.01 ns FWHM at 511 keV. The spatial resolution was measured using maximum likelihood expectation maximization reconstruction of a grid of point sources suspended in warm background. The averaged resolution over the central 6 cm of the FOV is 1.01 ± 0.13 mm in the X-direction, 1.84 ± 0.20 mm in the Y-direction, and 0.84 ± 0.11 mm in the Z-direction. Quantitative analysis of acquired micro-Derenzo phantom images shows better than 1.2 mm resolution at the center of the FOV, with subsequent resolution degradation in the y-direction toward the edge of the FOV caused by limited angle tomography effects.

    View details for DOI 10.1109/TMI.2018.2799619

    View details for Web of Science ID 000428886700021

    View details for PubMedID 29621003

  • Standard OSEM vs. regularized PET image reconstruction: qualitative and quantitative comparison using phantom data and various clinical radiopharmaceuticals AMERICAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Lantos, J., Mittra, E. S., Levin, C. S., Iagaru, A. 2018; 8 (2): 110–18


    We investigated the block sequential regularized expectation maximization (BSREM) algorithm. ACR phantom measurements with different count statistics and 60 PET/CT research scans from the GE Discovery 600 and 690 scanners were reconstructed using BSREM and the standard-of-care OSEM algorithm. Hot concentration recovery and cold contrast recovery were measured from the phantom data. Two experienced nuclear medicine physicians reviewed the clinical images blindly. Liver SNR liver and SUVmax of the smallest lesion detected in each patient were also measured. The relationship between the maximum and mean hot concentration recovery remained monotonic below 1.5 maximum concentration recovery. The mean cold contrast recovery remained stable even for decreasing statistics with a highest absolute difference of 4% in air and 2% in bone for each reconstruction method. The D600 images resulted in an average 30% higher SNR than the D690 data for BSREM; there was no difference in SNR results between the two scanners with OSEM. The small lesion SUVmax values on the BSREM images with β of 250, 350 and 450, respectively were on average 80%, 60% and 43% (D690) and 42%, 29%, and 21% (D600) higher than in the case of OSEM. In conclusion, BSREM can outperform OSEM in terms of contrast recovery and organ uniformity over a range of PET tracers, but a task dependent regularization strength parameter (beta) selection may be necessary. To avoid image noise and artifacts, our results suggest that using higher beta values (at least 350) may be appropriate, especially if the data has low count statistics.

    View details for PubMedID 29755844

    View details for PubMedCentralID PMC5944826

  • Performance study of a radio-frequency field-penetrable PET insert for simultaneous PET/MRI. IEEE transactions on radiation and plasma medical sciences Chang, C. M., Lee, B. J., Grant, A. M., Groll, A. N., Levin, C. S. 2018; 2 (5): 422–31


    Hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) has risen to the cutting edge of medical imaging technology as it allows simultaneous acquisition of structural, functional and molecular information of the patient. A PET insert that can be installed into existing MR systems can in principle reduce the cost barriers for an existing MR site to achieve simultaneous PET/MRI compared to procuring an integrated PET+MRI system. The PET insert systems developed so far for PET/MRI require the RF transmitter coil to reside inside the PET ring as those PET inserts block the RF fields from the MRI system. Here we report for the first time on the performance of a full-ring brain-sized "RF-penetrable" PET insert we have recently completed. This insert allows the RF fields generated by the built-in body coil to penetrate the PET ring. The PET insert comprises a ring of 16 detector modules employing electro-optical coupled signal transmission and a multiplexing framework based on compressed sensing. Energy resolution, coincidence timing resolution (CTR), photopeak position, and coincidence count rate were acquired outside and inside a 3-Tesla MRI system under simultaneous acquisition to evaluate the impact of MRI on the PET performance. Coincidence count rate performance was evaluated by acquiring a cylinder source with high initial activity decaying over time. Tomographic imaging of two phantoms, a custom 6.5-cm diameter resolution phantom with hot rods of four different sizes (2.8 mm, 3.2 mm, 4.2 mm, and 5.2 mm diameter) and a 3D Hoffman brain phantom, were performed to evaluate the imaging capability of the PET insert. The energy resolution at 511 keV and CTR acquired by the PET insert were 16.2±0.1% and 5.3±0.1 ns FWHM, respectively, and remained stable during MRI operation except when the EPI sequence was applied. The PET system starts to show saturation in coincidence count rate at 2.76 million photon counts per second. Most of the 2.8-mm diameter hot rods and main features of the 3D Hoffman brain phantom were resolved by the PET insert, demonstrating its high spatial resolution and capability to image a complex tracer distribution mimicking that seen in the human brain.

    View details for PubMedID 30911706

  • Positioning true coincidences that undergo inter-and intra-crystal scatter for a sub-mm resolution cadmium zinc telluride-based PET system PHYSICS IN MEDICINE AND BIOLOGY Abbaszadeh, S., Chinn, G., Levin, C. S. 2018; 63 (2): 025012


    The kinematics of Compton scatter can be used to estimate the interaction sequence of inter-crystal scatter interactions in 3D position-sensitive cadmium zinc telluride (CZT) detectors. However, in the case of intra-crystal scatter in a 'cross-strip' CZT detector slab, multiple anode and cathode strips may be triggered, creating position ambiguity due to uncertainty in possible combinations of anode-cathode pairings. As a consequence, methods such as energy-weighted centroid are not applicable to position the interactions. In practice, since the event position is uncertain, these intra-crystal scatters events are discarded. In this work, we studied using Compton kinematics and a 'direction difference angle' to provide a method to correctly identify the anode-cathode pair corresponding to the first interaction position in an intra-crystal scatter event. GATE simulation studies of a NEMA NU4 image quality phantom in a small animal positron emission tomography under development composed of 192, [Formula: see text] mm CZT crystals shows that 47% of total numbers of multiple-interaction photon events (MIPEs) are intra-crystal scatter with a 100 keV lower energy threshold per interaction. The sensitivity of the system increases from 0.6 to 4.10 (using 10 keV as system lower energy threshold) by including rather than discarding inter- and intra-crystal scatter. The contrast-to-noise ratio (CNR) also increases from [Formula: see text] to [Formula: see text]. It was shown that a higher energy threshold limits the capability of the system to detect MIPEs and reduces CNR. Results indicate a sensitivity increase (4.1 to 5.88) when raising the lower energy threshold (10 keV to 100 keV) for the case of only two-interaction events. In order to detect MIPEs accurately, a low noise system capable of a low energy threshold (10 keV) per interaction is desired.

    View details for DOI 10.1088/1361-6560/aa9a2b

    View details for Web of Science ID 000419796600012

    View details for PubMedID 29131809

    View details for PubMedCentralID PMC5785233

  • Clinical evaluation of TOF versus non-TOF on PET artifacts in simultaneous PET/MR: a dual centre experience. European journal of nuclear medicine and molecular imaging Ter Voert, E. E., Veit-Haibach, P., Ahn, S., Wiesinger, F., Khalighi, M. M., Levin, C. S., Iagaru, A. H., Zaharchuk, G., Huellner, M., Delso, G. 2017; 44 (7): 1223-1233


    Our objective was to determine clinically the value of time-of-flight (TOF) information in reducing PET artifacts and improving PET image quality and accuracy in simultaneous TOF PET/MR scanning.A total 65 patients who underwent a comparative scan in a simultaneous TOF PET/MR scanner were included. TOF and non-TOF PET images were reconstructed, clinically examined, compared and scored. PET imaging artifacts were categorized as large or small implant-related artifacts, as dental implant-related artifacts, and as implant-unrelated artifacts. Differences in image quality, especially those related to (implant) artifacts, were assessed using a scale ranging from 0 (no artifact) to 4 (severe artifact).A total of 87 image artifacts were found and evaluated. Four patients had large and eight patients small implant-related artifacts, 27 patients had dental implants/fillings, and 48 patients had implant-unrelated artifacts. The average score was 1.14 ± 0.82 for non-TOF PET images and 0.53 ± 0.66 for TOF images (p < 0.01) indicating that artifacts were less noticeable when TOF information was included.Our study indicates that PET image artifacts are significantly mitigated with integration of TOF information in simultaneous PET/MR. The impact is predominantly seen in patients with significant artifacts due to metal implants.

    View details for DOI 10.1007/s00259-017-3619-2

    View details for PubMedID 28124091

  • Low eddy current RF shielding enclosure designs for 3T MR applications. Magnetic resonance in medicine Lee, B. J., Watkins, R. D., Chang, C., Levin, C. S. 2017


    Magnetic resonance-compatible medical devices operate within the MR environment while benefitting from the superior anatomic information of MRI. Avoiding electromagnetic interference between such instrumentation and the MR system is crucial. In this work, various shielding configurations for positron emission tomography (PET) detectors were studied and analyzed regarding radiofrequency (RF) shielding effectiveness and gradient-induced eddy current performances. However, the results of this work apply to shielding considerations for any MR-compatible devices.Six shielding enclosure configurations with various thicknesses, patterns, and materials were designed: solid and segmented copper, phosphor bronze mesh (PBM), and carbon fiber composite (CFC). A series of tests was performed on RF shielding effectiveness and the gradient-induced eddy current.For the shielding effectiveness, the solid copper with various thickness and PBM configurations yield significantly better shielding effectiveness (>15 dB) compared with CFC and segmented configurations. For the gradient-induced eddy current performance, the solid copper shielding configurations with different thicknesses showed significantly worse results, up to a factor of 3.89 dB, compared with the segmented copper, PBM, and the CFC configurations.We evaluated the RF shielding effectiveness and the gradient-induced eddy current artifacts of several shielding designs, and only the PBM showed positive outcomes for both aspects. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26766

    View details for PubMedID 28585334

  • Studies of a Next Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT System. Journal of nuclear medicine Hsu, D. F., Ilan, E., Peterson, W. T., Uribe, J., Lubberink, M., Levin, C. S. 2017


    This article presents system performance studies of the Discovery MI PET/CT system, a new time-of-flight (TOF) system based on silicon photomultipliers. System performance and clinical imaging comparisons were made between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different reconstruction algorithms. Methods: Spatial resolution, sensitivity, NECR, scatter fraction, count rate accuracy, and image quality were characterized with the NEMA NU-2 2012 standards. Energy and coincidence time resolution were measured. Tests were conducted independently and results were averaged on two Discovery MI scanners installed at Stanford and Uppsala University Hospitals. Back-to-back patient scans were also performed between the Discovery MI PET/CT, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed with both ordered-subset expectation maximization (OSEM) and the "Q.Clear" reconstruction algorithms, and examined qualitatively. Results: The averaged full-width half max (FWHM) of the radial/tangential/axial spatial resolution reconstructed with FBP at 1, 10, and 20 cm from the system center are, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity is 13.7 cps/kBq at the center of the FOV. Averaged peak noise equivalent count rate is 193.4 kcps at 21.9 kBq/mL with a scatter fraction of 40.6%. The averaged contrast recovery coefficients for the image quality phantom are 53.7/64.0/73.1/82.7/86.8/90.7 for the 10/13/17/22/28/37 mm diameter spheres. The average photopeak energy resolution is 9.40% FWHM and the average coincidence time resolution is 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrate the high quality of the Discovery MI system. Comparisons between the Discovery MI and SIGNA systems show similar spatial resolution and overall imaging performance. Lastly, results indicate significant image quality and contrast-to-noise performance enhancement for the "Q.Clear" reconstruction algorithm when compared to OSEM. Conclusion: Excellent performance was achieved with the new Discovery MI system, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between different image reconstruction algorithms and other multimodal SiPM and non-SiPM-based PET detector system designs indicate substantial performance enhancements are possible with this next-generation system.

    View details for DOI 10.2967/jnumed.117.189514

    View details for PubMedID 28450566