Craig Levin

All Publications

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)
View details for DOI 10.1088/1361-6560/ab0da6

View details for Web of Science ID 000480292700013
Electronics method to advance the coincidence time resolution with bismuth germanate. Physics in medicine and biology Cates, J. W., Levin, C. S. 2019
Abstract

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 mm2 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 mm3 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
View details for DOI 10.1109/TRPMS.2018.2885704

View details for Web of Science ID 000467062000005
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)
View details for DOI 10.1088/1361-6560/ab115b

View details for Web of Science ID 000466862700003
Intercrystal scatter studies for a 1 mm3 resolution clinical PET system prototype. Physics in medicine and biology Hsu, D. F., Freese, D. L., Innes, D. R., Levin, C. S. 2019
Abstract

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 mm3 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
Abstract

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
Abstract

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
Abstract

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
Abstract

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 $B_{1}$ uniformity within the PET insert, and MR image quality, were analyzed with and without the PET ring present. The simulated and experimentally measured RF field attenuation factors with the PET ring present were -2.7 and -3.2 dB, respectively. The magnetic susceptibility effect (0.063 ppm) and noise emitted from the PET ring in the MR receive channel were insignificant. $B_{1}$ homogeneity of a spherical agar phantom within the PET ring FOV dropped by 8.4% and MR image SNR was reduced by 3.5 and 4.3 dB with the PET present for gradient-recalled echo and fast-spin echo, respectively. This paper demonstrates, for the first time, an RF-penetrable PET insert comprising a full ring of operating detectors that achieves simultaneous PET/MR using the standard built-in body coil as the RF transmitter.

View details for DOI 10.1109/TMI.2018.2815620

View details for Web of Science ID 000443877100010

View details for PubMedID 29993864
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
View details for DOI 10.1109/TRPMS.2018.2852686

View details for Web of Science ID 000456150700004
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
Abstract

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 mm2 FBK NUV SiPM. SPTR for large area devices was also significantly improved. The measured SPTRs for 3x3 mm2 Hamamatsu and SensL SiPMs were ≤150 ps FWHM, and SPTR ≤100 ps FWHM was measured for 3x3 mm2 and 4x4 mm2 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
Abstract

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 mm3 crystals coupled to rows of 3x3 mm2 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 mm2 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
Abstract

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
Abstract

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
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
Abstract

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
Ionizing radiation induces femtosecond time scale modulations of a material's optical properties Tao, L., Coffee, R., Levin, C. S., Grim, G. P., Furenlid, L. R., Barber, H. B. SPIE-INT SOC OPTICAL ENGINEERING. 2018
View details for DOI 10.1117/12.2319435

View details for Web of Science ID 000452820500002
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
Abstract

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
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
Abstract

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
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
Abstract

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
Abstract

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
Abstract

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
Robust Timing Calibration for PET Using L1-Norm Minimization. IEEE transactions on medical imaging Freese, D., Hsu, D., Innes, D., Levin, C. 2017
Abstract

Positron emission tomography (PET) relies on accurate timing information to pair two 511-keV photons into a coincidence event. Calibration of time delays between detectors becomes increasingly important as the timing resolution of detector technology improves, as a calibration error can quickly become a dominant source of error. Previous work has shown that the maximum likelihood estimate of these delays can be calculated by least squares estimation, but an approach is not tractable for complex systems and degrades in the presence of randoms. We demonstrate the original problem to be solvable iteratively using the LSMR algorithm. Using the LSMR, we solve for 60 030 delay parameters, including energy-dependent delays, in 4.5 s, using 1 000 000 coincidence events for a two-panel system dedicated to clinical locoregional imaging. We then extend the original least squares problem to be robust to random coincidences and low statistics by implementing l1-norm minimization using the alternating direction method of the multipliers (ADMM) algorithm. The ADMM algorithm converges after six iterations, or 20.6 s, and improves the timing resolution from 64.7 ± 0.1s full width at half maximum (FWHM) uncalibrated to 15.63 ± 0.02ns FWHM. We also demonstrate this algorithm's applicability to commercial systems using a GE Discovery 690 PET/CT. We scan a rotating transmission source, and after subtracting the 511-keV photon time-of-flight due to the source position, we calculate 13 824 per-crystal delays using 5 000 000 coincidence events in 3.78 s with three iterations, while showing a timing resolution improvement that is significantly better than previous calibration methods in the literature.

View details for DOI 10.1109/TMI.2017.2681939

View details for PubMedID 28320653
Time-over-threshold for pulse shape discrimination in a time-of-flight phoswich PET detector PHYSICS IN MEDICINE AND BIOLOGY Chang, C., Cates, J. W., Levin, C. S. 2017; 62 (1): 258-271
Abstract

It is well known that a PET detector capable of measuring both photon time-of-flight (TOF) and depth-of-interaction (DOI) improves the image quality and accuracy. Phoswich designs have been realized in PET detectors to measure DOI for more than a decade. However, PET detectors based on phoswich designs put great demand on the readout circuits, which have to differentiate the pulse shape produced by different crystal layers. A simple pulse shape discrimination approach is required to realize the phoswich designs in a clinical PET scanner, which consists of thousands of scintillation crystal elements. In this work, we studied time-over-threshold (ToT) as a pulse shape parameter for DOI. The energy, timing and DOI performance were evaluated for a phoswich detector design comprising [Formula: see text] mm LYSO:Ce crystal optically coupled to [Formula: see text] mm calcium co-doped LSO:Ce,Ca(0.4%) crystal read out by a silicon photomultiplier (SiPM). A DOI accuracy of 97.2% has been achieved for photopeak events using the proposed time-over-threshold (ToT) processing. The energy resolution without correction for SiPM non-linearity was [Formula: see text]% and [Formula: see text]% FWHM at 511 keV for LYSO and LSO crystal layers, respectively. The coincidence time resolution for photopeak events ranges from 164.6 ps to 183.1 ps FWHM, depending on the layer combinations. The coincidence time resolution for inter-crystal scatter events ranges from 214.6 ps to 418.3 ps FWHM, depending on the energy windows applied. These results show great promises of using ToT for pulse shape discrimination in a TOF phoswich detector since a ToT measurement can be easily implemented in readout electronics.

View details for DOI 10.1088/1361-6560/62/1/258

View details for Web of Science ID 000391567700007

View details for PubMedID 27991437

View details for PubMedCentralID PMC5280037
Simultaneous PET/MR imaging with a radio frequency-penetrable PET insert. Medical physics Grant, A. M., Lee, B. J., Chang, C., Levin, C. S. 2017; 44 (1): 112-120
Abstract

A brain sized radio frequency (RF)-penetrable PET insert has been designed for simultaneous operation with MRI systems. This system takes advantage of electro-optical coupling and battery power to electrically float the PET insert relative to the MRI ground, permitting RF signals to be transmitted through small gaps between the modules that form the PET ring. This design facilitates the use of the built-in body coil for RF transmission and thus could be inserted into any existing MR site wishing to achieve simultaneous PET/MR imaging. The PET detectors employ nonmagnetic silicon photomultipliers in conjunction with a compressed sensing signal multiplexing scheme, and optical fibers to transmit analog PET detector signals out of the MRI room for decoding, processing, and image reconstruction.The PET insert was first constructed and tested in a laboratory benchtop setting, where tomographic images of a custom resolution phantom were successfully acquired. The PET insert was then placed within a 3T body MRI system, and tomographic resolution/contrast phantom images were acquired both with only the B0 field present, and under continuous pulsing from different MR imaging sequences.The resulting PET images have comparable contrast-to-noise ratios (CNR) under all MR pulsing conditions: The maximum percent CNR relative difference for each rod type among all four PET images acquired in the MRI system has a mean of 14.0 ± 7.7%. MR images were successfully acquired through the RF-penetrable PET shielding using only the built-in MR body coil, suggesting that simultaneous imaging is possible without significant mutual interference.These results show promise for this technology as an alternative to costly integrated PET/MR scanners; a PET insert that is compatible with any existing clinical MRI system could greatly increase the availability, accessibility, and dissemination of PET/MR.

View details for DOI 10.1002/mp.12031

View details for PubMedID 28102949

View details for PubMedCentralID PMC5372382
An Expectation Maximization Method for Joint Estimation of Emission Activity Distribution and Photon Attenuation Map in PET IEEE TRANSACTIONS ON MEDICAL IMAGING Mihlin, A., Levin, C. S. 2017; 36 (1): 214-224
Abstract

A maximum likelihood expectation maximization (MLEM) method is proposed for joint estimation of emission activity distribution and photon attenuation map from positron emission tomography (PET) emission data alone. The method is appealing since: (i) it guarantees monotonic likelihood increase to a local extremum, (ii) does not require arbitrary parameters, and (iii) guarantees the positivity of the estimated distributions. Moreover, we propose a discrete Poisson data acquisition model and numerical algorithm for: (i) efficient graphics processing unit (GPU) based formulation, and (ii) a closed form exact solution for the MLEM update equations, which is essential for accurate and robust estimation. Numerical experiments indicate that in the presence of noise, joint EMAA estimation converges to the true emission activity distribution with root mean square errors of 4% and 0.5% respectively in estimation of lung- and myocardial emission activity distributions for a computational XCAT thorax phantom.

View details for DOI 10.1109/TMI.2016.2602339

View details for Web of Science ID 000392418000019

View details for PubMedID 27576244
Study of material properties important for an optical property modulation-based radiation detection method for positron emission tomography. Journal of medical imaging (Bellingham, Wash.) Tao, L., Daghighian, H. M., Levin, C. S. 2017; 4 (1): 011010-?
Abstract

We compare the performance of two detector materials, cadmium telluride (CdTe) and bismuth silicon oxide (BSO), for optical property modulation-based radiation detection method for positron emission tomography (PET), which is a potential new direction to dramatically improve the annihilation photon pair coincidence time resolution. We have shown that the induced current flow in the detector crystal resulting from ionizing radiation determines the strength of optical modulation signal. A larger resistivity is favorable for reducing the dark current (noise) in the detector crystal, and thus the higher resistivity BSO crystal has a lower (50% lower on average) noise level than CdTe. The CdTe and BSO crystals can achieve the same sensitivity under laser diode illumination at the same crystal bias voltage condition while the BSO crystal is not as sensitive to 511-keV photons as the CdTe crystal under the same crystal bias voltage. The amplitude of the modulation signal induced by 511-keV photons in BSO crystal is around 30% of that induced in CdTe crystal under the same bias condition. In addition, we have found that the optical modulation strength increases linearly with crystal bias voltage before saturation. The modulation signal with CdTe tends to saturate at bias voltages higher than 1500 V due to its lower resistivity (thus larger dark current) while the modulation signal strength with BSO still increases after 3500 V. Further increasing the bias voltage for BSO could potentially further enhance the modulation strength and thus, the sensitivity.

View details for DOI 10.1117/1.JMI.4.1.011010

View details for PubMedID 28180132

View details for PubMedCentralID PMC5286320
Highly multiplexed signal readout for a time-of-flight positron emission tomography detector based on silicon photomultipliers. Journal of medical imaging (Bellingham, Wash.) Cates, J. W., Bieniosek, M. F., Levin, C. S. 2017; 4 (1): 011012-?
Abstract

Maintaining excellent timing resolution in the generation of silicon photomultiplier (SiPM)-based time-of-flight positron emission tomography (TOF-PET) systems requires a large number of high-speed, high-bandwidth electronic channels and components. To minimize the cost and complexity of a system's back-end architecture and data acquisition, many analog signals are often multiplexed to fewer channels using techniques that encode timing, energy, and position information. With progress in the development SiPMs having lower dark noise, after pulsing, and cross talk along with higher photodetection efficiency, a coincidence timing resolution (CTR) well below 200 ps FWHM is now easily achievable in single pixel, bench-top setups using 20-mm length, lutetium-based inorganic scintillators. However, multiplexing the output of many SiPMs to a single channel will significantly degrade CTR without appropriate signal processing. We test the performance of a PET detector readout concept that multiplexes 16 SiPMs to two channels. One channel provides timing information with fast comparators, and the second channel encodes both position and energy information in a time-over-threshold-based pulse sequence. This multiplexing readout concept was constructed with discrete components to process signals from a [Formula: see text] array of SensL MicroFC-30035 SiPMs coupled to [Formula: see text] Lu1.8Gd0.2SiO5 (LGSO):Ce (0.025 mol. %) scintillators. This readout method yielded a calibrated, global energy resolution of 15.3% FWHM at 511 keV with a CTR of [Formula: see text] FWHM between the 16-pixel multiplexed detector array and a [Formula: see text] LGSO-SiPM reference detector. In summary, results indicate this multiplexing scheme is a scalable readout technique that provides excellent coincidence timing performance.

View details for DOI 10.1117/1.JMI.4.1.011012

View details for PubMedID 28382312
New-generation small animal positron emission tomography system for molecular imaging. Journal of medical imaging (Bellingham, Wash.) Abbaszadeh, S., Levin, C. S. 2017; 4 (1): 011008-?
Abstract

The next generation of discoveries in molecular imaging requires positron emission tomography (PET) systems with high spatial resolution and high sensitivity to visualize and quantify low concentrations of molecular probes. The goal of this work is to assemble and explore such a system. We use cadmium zinc telluride (CZT) to achieve high spatial resolution, three-dimensional interaction positioning, and excellent energy resolution. The CZT crystals are arranged in an edge-on configuration with a minimum gap of [Formula: see text] in a four-sided panel geometry to achieve superior photon sensitivity. The developed CZT detectors and readout electronics were scaled up to complete significant portions of the final PET system. The steering electrode bias and the amplitude of the analog signals for time measurement were optimized to improve performance. The energy resolution (at 511 keV) over 468 channels is [Formula: see text] full-width-at-half-maximum (FWHM). The spatial resolution is [Formula: see text] FWHM. The time resolution of six CZT crystals in coincidence with six other CZT crystals is 37 ns. With high energy and spatial resolution and the relatively low random rate for small animal imaging, this system shows promise to be very useful for molecular imaging studies.

View details for DOI 10.1117/1.JMI.4.1.011008

View details for PubMedID 28097211

View details for PubMedCentralID PMC5228551
A multiplexed TOF and DOI capable PET detector using a binary position sensitive network. Physics in medicine and biology Bieniosek, M. F., CATES, J. W., Levin, C. S. 2016; 61 (21): 7639-7651
Abstract

Time of flight (TOF) and depth of interaction (DOI) capabilities can significantly enhance the quality and uniformity of positron emission tomography (PET) images. Many proposed TOF/DOI PET detectors require complex readout systems using additional photosensors, active cooling, or waveform sampling. This work describes a high performance, low complexity, room temperature TOF/DOI PET module. The module uses multiplexed timing channels to significantly reduce the electronic readout complexity of the PET detector while maintaining excellent timing, energy, and position resolution. DOI was determined using a two layer light sharing scintillation crystal array with a novel binary position sensitive network. A 20 mm effective thickness LYSO crystal array with four 3 mm × 3 mm silicon photomultipliers (SiPM) read out by a single timing channel, one energy channel and two position channels achieved a full width half maximum (FWHM) coincidence time resolution of 180 ± 2 ps with 10 mm of DOI resolution and 11% energy resolution. With sixteen 3 mm × 3 mm SiPMs read out by a single timing channel, one energy channel and four position channels a coincidence time resolution 204 ± 1 ps was achieved with 10 mm of DOI resolution and 15% energy resolution. The methods presented here could significantly simplify the construction of high performance TOF/DOI PET detectors.

View details for PubMedID 27740946
A promising new mechanism of ionizing radiation detection for positron emission tomography: modulation of optical properties. Physics in medicine and biology Tao, L., Daghighian, H. M., Levin, C. S. 2016; 61 (21): 7600-7622
Abstract

Using conventional scintillation detection, the fundamental limit in positron emission tomography (PET) time resolution is strongly dependent on the inherent temporal variances generated during the scintillation process, yielding an intrinsic physical limit for the coincidence time resolution of around 100 ps. On the other hand, modulation mechanisms of the optical properties of a material exploited in the optical telecommunications industry can be orders of magnitude faster. In this paper we borrow from the concept of optics pump-probe measurement to for the first time study whether ionizing radiation can produce modulations of optical properties, which can be utilized as a novel method for radiation detection. We show that a refractive index modulation of approximately [Formula: see text] is induced by interactions in a cadmium telluride (CdTe) crystal from a 511 keV photon source. Furthermore, using additional radionuclide sources, we show that the amplitude of the optical modulation signal varies linearly with both the detected event rate and average photon energy of the radiation source.

View details for PubMedID 27716640
Improvements in PET Image Quality in Time of Flight (TOF) Simultaneous PET/MRI. Molecular imaging and biology Minamimoto, R., Levin, C., Jamali, M., Holley, D., Barkhodari, A., Zaharchuk, G., Iagaru, A. 2016; 18 (5): 776-781
Abstract

An integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanner with time of flight (TOF) technology is now available for clinical use. The aim of this study is to evaluate the potential of TOF PET in PET/MRI to reduce artifacts in PET images when compared to non-TOF PET/MRI, TOF PET/X-ray computed tomography (CT), and non-TOF PET/CT.All patients underwent a single 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) injection, followed first by PET/CT, and subsequently by PET/MRI. PET/CT exams were requested as standard-of-care for oncological indications. Using the PET acquisitions datasets, 4 series of images (TOF PET/CT, non-TOF PET/CT, TOF PET/MRI, and non-TOF PET/MRI) were reconstructed. These image series were visually evaluated for: (1) dental metal artifacts, (2) breathing artifacts, and (3) pelvic artifacts due to scatter correction errors from high bladder [(18)F]FDG concentration. PET image quality was assessed by a 3-point scale (1-clinically significant artifact, 2-non clinically significant artifact, and 3-no artifact).Twenty-five patients (mean ± SD age: 56 ± 13 years old; female: 10, male: 15) were enrolled. TOF PET/MRI, non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT scores 2.8, 2.5, 2.4, and 2.3, respectively for the presence of dental artifacts, 2.8, 2.5, 2.2, and 1.9, respectively, for the presence of breathing artifacts, and 2.7, 1.7, 2.0, and 1.3, respectively, for the presence of pelvic artifacts TOF PET/MRI images showed the highest image quality scores among the 4 datasets of PET images.The superior timing resolution and resulting TOF capability of the new PET/MRI scanner improved PET image quality in this cohort by reducing artifacts compared to non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT.

View details for DOI 10.1007/s11307-016-0939-8

View details for PubMedID 26884058
MR Performance Comparison of a PET/MR System Before and After SiPM-Based Time-of-Flight PET Detector Insertion IEEE TRANSACTIONS ON NUCLEAR SCIENCE Khalighi, M. M., Delso, G., Maramraju, S. H., Deller, T. W., Levin, C. S., Glover, G. H. 2016; 63 (5): 2419-2423
View details for DOI 10.1109/TNS.2016.2529624

View details for Web of Science ID 000386229200001
Characterization of a sub-assembly of 3D position sensitive cadmium zinc telluride detectors and electronics from a sub-millimeter resolution PET system. Physics in medicine and biology Abbaszadeh, S., Gu, Y., Reynolds, P. D., Levin, C. S. 2016; 61 (18): 6733-6753
Abstract

Cadmium zinc telluride (CZT) offers key advantages for small animal positron emission tomography (PET), including high spatial and energy resolution and simple metal deposition for fabrication of very small pixel arrays. Previous studies have investigated the intrinsic spatial, energy, and timing resolution of an individual sub-millimeter resolution CZT detector. In this work we present the first characterization results of a system of these detectors. The 3D position sensitive dual-CZT detector module and readout electronics developed in our lab was scaled up to complete a significant portion of the final PET system. This sub-system was configured as two opposing detection panels containing a total of twelve [Formula: see text] mm monolithic CZT crystals for proof of concept. System-level characterization studies, including optimizing the trigger threshold of each channel's comparators, were performed. (68)Ge and (137)Cs radioactive isotopes were used to characterize the energy resolution of all 468 anode channels in the sub-system. The mean measured global 511 keV photopeak energy resolution over all anodes was found to be [Formula: see text]% FWHM after correction for photon interaction depth-dependent signal variation. The measured global time resolution was 37 ns FWHM, a parameter to be further optimized, and the intrinsic spatial resolution was 0.76 mm FWHM.

View details for PubMedID 27551981
An Expectation Maximization Method for Joint Estimation of Emission Activity Distribution and Photon Attenuation Map in PET. IEEE transactions on medical imaging Mihlin, A., Levin, C. 2016
Abstract

A maximum likelihood expectation maximization (MLEM) method is proposed for joint estimation of emission activity distribution and photon attenuation map from positron emission tomography (PET) emission data alone. The method is appealing since: (i) it guarantees monotonic likelihood increase to a local extremum, (ii) does not require arbitrary parameters, and (iii) guarantees the positivity of the estimated distributions. Moreover, we propose a discrete Poisson data acquisition model and numerical algorithm for: (i) efficient graphics processing unit (GPU) based formulation, and (ii) a closed form exact solution for the MLEM update equations, which is essential for accurate and robust estimation. Numerical experiments indicate that in the presence of noise, joint EMAA estimation converges to the true emission activity distribution with root mean square errors of 4% and 0.5% respectively in estimation of lung- and myocardial emission activity distributions for a computational XCAT thorax phantom.

View details for DOI 10.1109/TMI.2016.2602339

View details for PubMedID 28113621
Analog filtering methods improve leading edge timing performance of multiplexed SiPMs. Physics in medicine and biology Bieniosek, M. F., CATES, J. W., Grant, A. M., Levin, C. S. 2016; 61 (16): N427-40
Abstract

Multiplexing many SiPMs to a single readout channel is an attractive option to reduce the readout complexity of high performance time of flight (TOF) PET systems. However, the additional dark counts and shaping from each SiPM cause significant baseline fluctuations in the output waveform, degrading timing measurements using a leading edge threshold. This work proposes the use of a simple analog filtering network to reduce the baseline fluctuations in highly multiplexed SiPM readouts. With 16 SiPMs multiplexed, the FWHM coincident timing resolution for single [Formula: see text] mm LYSO crystals was improved from 401 ± 4 ps without filtering to 248 ± 5 ps with filtering. With 4 SiPMs multiplexed, using an array of [Formula: see text] mm LFS crystals the mean time resolution was improved from 436 ± 6 ps to 249 ± 2 ps. Position information was acquired with a novel binary positioning network. All experiments were performed at room temperature with no active temperature regulation. These results show a promising technique for the construction of high performance multiplexed TOF PET readout systems using analog leading edge timing pickoff.

View details for DOI 10.1088/0031-9155/61/16/N427

View details for PubMedID 27484131
Design Features and Mutual Compatibility Studies of the Time-of-Flight PET Capable GE SIGNA PET/MR System. IEEE transactions on medical imaging Levin, C. S., Maramraju, S. H., Khalighi, M. M., Deller, T. W., Delso, G., Jansen, F. 2016; 35 (8): 1907-1914
Abstract

A recent entry into the rapidly evolving field of integrated PET/MR scanners is presented in this paper: a whole body hybrid PET/MR system (SIGNA PET/MR, GE Healthcare) capable of simultaneous acquisition of both time-of-flight (TOF) PET and high resolution MR data. The PET ring was integrated into an existing 3T MR system resulting in a (patient) bore opening of 60 cm diameter, with a 25 cm axial FOV. PET performance was evaluated both on the standalone PET ring and on the same detector integrated into the MR system, to assess the level of mutual interference between both subsystems. In both configurations we obtained detector performance data. PET detector performance was not significantly affected by integration into the MR system. The global energy resolution was within 2% (10.3% versus 10.5%), and the system coincidence time resolution showed a maximum change of < 3% (385 ps versus 394 ps) when measured outside MR and during simultaneous PET/MRI acquisitions, respectively. To evaluate PET image quality and resolution, the NEMA IQ phantom was acquired with MR idle and with MR active. Impact of PET on MR IQ was assessed by comparing SNR with PET acquisition on and off. B0 and B1 homogeneities were acquired before and after the integration of the PET ring inside the magnet. In vivo brain and whole body head-to-thighs data were acquired to demonstrate clinical image quality.

View details for DOI 10.1109/TMI.2016.2537811

View details for PubMedID 26978664
NEMA NU 2-2012 performance studies for the SiPM-based ToF-PET component of the GE SIGNA PET/MR system MEDICAL PHYSICS Grant, A. M., Deller, T. W., Khalighi, M. M., Maramraju, S. H., Delso, G., Levin, C. S. 2016; 43 (5)
Abstract

The GE SIGNA PET/MR is a new whole body integrated time-of-flight (ToF)-PET/MR scanner from GE Healthcare. The system is capable of simultaneous PET and MR image acquisition with sub-400 ps coincidence time resolution. Simultaneous PET/MR holds great potential as a method of interrogating molecular, functional, and anatomical parameters in clinical disease in one study. Despite the complementary imaging capabilities of PET and MRI, their respective hardware tends to be incompatible due to mutual interference. In this work, the GE SIGNA PET/MR is evaluated in terms of PET performance and the potential effects of interference from MRI operation.The NEMA NU 2-2012 protocol was followed to measure PET performance parameters including spatial resolution, noise equivalent count rate, sensitivity, accuracy, and image quality. Each of these tests was performed both with the MR subsystem idle and with continuous MR pulsing for the duration of the PET data acquisition. Most measurements were repeated at three separate test sites where the system is installed.The scanner has achieved an average of 4.4, 4.1, and 5.3 mm full width at half maximum radial, tangential, and axial spatial resolutions, respectively, at 1 cm from the transaxial FOV center. The peak noise equivalent count rate (NECR) of 218 kcps and a scatter fraction of 43.6% are reached at an activity concentration of 17.8 kBq/ml. Sensitivity at the center position is 23.3 cps/kBq. The maximum relative slice count rate error below peak NECR was 3.3%, and the residual error from attenuation and scatter corrections was 3.6%. Continuous MR pulsing had either no effect or a minor effect on each measurement.Performance measurements of the ToF-PET whole body GE SIGNA PET/MR system indicate that it is a promising new simultaneous imaging platform.

View details for DOI 10.1118/1.4945416

View details for Web of Science ID 000378924200034

View details for PubMedID 27147345
Achieving fast timing performance with multiplexed SiPMs. Physics in medicine and biology Bieniosek, M. F., CATES, J. W., Levin, C. S. 2016; 61 (7): 2879-2892
Abstract

Using time of flight (ToF) measurements for positron emission tomography (PET) is an attractive avenue for increasing the signal to noise (SNR) ratio of PET images. However, achieving excellent time resolution required for high SNR gain using silicon photomultipliers (SiPM) requires many resource heavy high bandwidth readout channels. A method of multiplexing many SiPM signals into a single electronic channel would greatly simplify ToF PET systems. However, multiplexing SiPMs degrades time resolution because of added dark counts and signal shaping. In this work the relative contribution of dark counts and signal shaping to timing degradation is simulated and a baseline correction technique to mitigate the effect of multiplexing on the time resolution of analog SiPMs is simulated and experimentally verified. A charge sharing network for multiplexing is proposed and tested. Results show a full width at half maximum (FWHM) coincidence time resolution of [Formula: see text] ps for a single 3 mm × 3 mm × 20 mm LYSO scintillation crystals coupled to an array of sixteen 3 mm × 3 mm SiPMs that are multiplexed to a single timing channel (in addition to 4 position channels). A [Formula: see text] array of 3 mm × 3 mm × 20 mm LFS crystals showed an average FWHM coincidence time resolution of [Formula: see text] ps using the same timing scheme. All experiments were performed at room temperature with no thermal regulation. These results show that excellent time resolution for ToF can be achieved with a highly multiplexed analog SiPM readout.

View details for DOI 10.1088/0031-9155/61/7/2879

View details for PubMedID 26987898
Advances in coincidence time resolution for PET. Physics in medicine and biology Cates, J. W., Levin, C. S. 2016; 61 (6): 2255-2264
Abstract

Coincidence time resolution (CTR), an important parameter for time-of-flight (TOF) PET performance, is determined mainly by properties of the scintillation crystal and photodetector used. Stable production techniques for LGSO:Ce (Lu1.8Gd0.2SiO5:Ce) with decay times varying from ∼30-40 ns have been established over the past decade, and the decay time can be accurately controlled with varying cerium concentration (0.025-0.075 mol%). This material is promising for TOF-PET, as it has similar light output and equivalent stopping power for 511 keV annihilation photons compared to industry standard LSO:Ce and LYSO:Ce, and the decay time is improved by more than 30% with proper Ce concentration. This work investigates the achievable CTR with LGSO:Ce (0.025 mol%) when coupled to new silicon photomultipliers. Crystal element dimension is another important parameter for achieving fast timing. 20 mm length crystal elements achieve higher 511 keV photon detection efficiency, but also introduce higher scintillation photon transit time variance. 3 mm length crystals are not practical for PET, but have reduced scintillation transit time spread. The CTR between pairs of [Formula: see text] mm(3)and [Formula: see text] mm(3) LGSO:Ce crystals was measured to be [Formula: see text] and [Formula: see text] ps FWHM, respectively. Measurements of light yield and intrinsic decay time are also presented for a thorough investigation into the timing performance with LGSO:Ce (0.025 mol%).

View details for DOI 10.1088/0031-9155/61/6/2255

View details for PubMedID 26914187
Breast-Dedicated Radionuclide Imaging Systems. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Hsu, D. F., Freese, D. L., Levin, C. S. 2016; 57: 40S-5S
Abstract

Breast-dedicated radionuclide imaging systems show promise for increasing clinical sensitivity for breast cancer while minimizing patient dose and cost. We present several breast-dedicated coincidence-photon and single-photon camera designs that have been described in the literature and examine their intrinsic performance, clinical relevance, and impact. Recent tracer development is mentioned, results from recent clinical tests are summarized, and potential areas for improvement are highlighted.

View details for DOI 10.2967/jnumed.115.157883

View details for PubMedID 26834101
The potential of TOF PET-MRI for reducing artifacts in PET images. EJNMMI physics Iagaru, A., Minamimoto, R., Levin, C., Barkhodari, A., Jamali, M., Holley, D., Greg, Z. 2015; 2: A77-?
View details for DOI 10.1186/2197-7364-2-S1-A77

View details for PubMedID 26956338

View details for PubMedCentralID PMC4798707
Successful demonstration of simultaneous PET/MR Imaging with a RF-penetrable PET insert. EJNMMI physics Lee, B., Grant, A., Chang, C., Glover, G., Levin, C. 2015; 2: A17-?
View details for DOI 10.1186/2197-7364-2-S1-A17

View details for PubMedID 26956272

View details for PubMedCentralID PMC4798708
Technical Note: Characterization of custom 3D printed multimodality imaging phantoms. Medical physics Bieniosek, M. F., Lee, B. J., Levin, C. S. 2015; 42 (10): 5913-?
Abstract

Imaging phantoms are important tools for researchers and technicians, but they can be costly and difficult to customize. Three dimensional (3D) printing is a widely available rapid prototyping technique that enables the fabrication of objects with 3D computer generated geometries. It is ideal for quickly producing customized, low cost, multimodal, reusable imaging phantoms. This work validates the use of 3D printed phantoms by comparing CT and PET scans of a 3D printed phantom and a commercial "Micro Deluxe" phantom. This report also presents results from a customized 3D printed PET/MRI phantom, and a customized high resolution imaging phantom with sub-mm features.CT and PET scans of a 3D printed phantom and a commercial Micro Deluxe (Data Spectrum Corporation, USA) phantom with 1.2, 1.6, 2.4, 3.2, 4.0, and 4.8 mm diameter hot rods were acquired. The measured PET and CT rod sizes, activities, and attenuation coefficients were compared. A PET/MRI scan of a custom 3D printed phantom with hot and cold rods was performed, with photon attenuation and normalization measurements performed with a separate 3D printed normalization phantom. X-ray transmission scans of a customized two level high resolution 3D printed phantom with sub-mm features were also performed.Results show very good agreement between commercial and 3D printed micro deluxe phantoms with less than 3% difference in CT measured rod diameter, less than 5% difference in PET measured rod diameter, and a maximum of 6.2% difference in average rod activity from a 10 min, 333 kBq/ml (9 μCi/ml) Siemens Inveon (Siemens Healthcare, Germany) PET scan. In all cases, these differences were within the measurement uncertainties of our setups. PET/MRI scans successfully identified 3D printed hot and cold rods on PET and MRI modalities. X-ray projection images of a 3D printed high resolution phantom identified features as small as 350 μm wide.This work shows that 3D printed phantoms can be functionally equivalent to commercially available phantoms. They are a viable option for quickly distributing and fabricating low cost, customized phantoms.

View details for DOI 10.1118/1.4930803

View details for PubMedID 26429265

View details for PubMedCentralID PMC4575317
Programmable High Voltage Distribution for Photodetectors in a 1 mm Resolution Clinical PET System IEEE TRANSACTIONS ON NUCLEAR SCIENCE Lau, F. W., Vandenbroucke, A., Yeom, J., Reynolds, P. D., Hsu, D., Innes, D., Levin, C. S. 2015; 62 (5): 1989-1994
View details for DOI 10.1109/TNS.2015.2440437

View details for Web of Science ID 000363242200008
Performance characterization of compressed sensing positron emission tomography detectors and data acquisition system. Physics in medicine and biology Chang, C., Grant, A. M., Lee, B. J., Kim, E., Hong, K., Levin, C. S. 2015; 60 (16): 6407-6421
Abstract

In the field of information theory, compressed sensing (CS) had been developed to recover signals at a lower sampling rate than suggested by the Nyquist-Shannon theorem, provided the signals have a sparse representation with respect to some base. CS has recently emerged as a method to multiplex PET detector readouts thanks to the sparse nature of 511 keV photon interactions in a typical PET study. We have shown in our previous numerical studies that, at the same multiplexing ratio, CS achieves higher signal-to-noise ratio (SNR) compared to Anger and cross-strip multiplexing. In addition, unlike Anger logic, multiplexing by CS preserves the capability to resolve multi-hit events, in which multiple pixels are triggered within the resolving time of the detector. In this work, we characterized the time, energy and intrinsic spatial resolution of two CS detectors and a data acquisition system we have developed for a PET insert system for simultaneous PET/MRI. The CS detector comprises a [Formula: see text] mosaic of [Formula: see text] arrays of [Formula: see text] mm(3) lutetium-yttrium orthosilicate crystals coupled one-to-one to eight [Formula: see text] silicon photomultiplier arrays. The total number of 128 pixels is multiplexed down to 16 readout channels by CS. The energy, coincidence time and intrinsic spatial resolution achieved by two CS detectors were [Formula: see text]% FWHM at 511 keV, 4.5 ns FWHM and 2.3 mm FWHM, respectively. A series of experiments were conducted to measure the sources of time jitter that limit the time resolution of the current system, which provides guidance for potential system design improvements. These findings demonstrate the feasibility of compressed sensing as a promising multiplexing method for PET detectors.

View details for DOI 10.1088/0031-9155/60/16/6407

View details for PubMedID 26237671
Optical delay encoding for fast timing and detector signal multiplexing in PET MEDICAL PHYSICS Grant, A. M., Levin, C. S. 2015; 42 (8): 4526-4535
Abstract

The large number of detector channels in modern positron emission tomography (PET) scanners poses a challenge in terms of readout electronics complexity. Multiplexing schemes are typically implemented to reduce the number of physical readout channels, but often result in performance degradation. Novel methods of multiplexing in PET must be developed to avoid this data degradation. The preservation of fast timing information is especially important for time-of-flight PET.A new multiplexing scheme based on encoding detector interaction events with a series of extremely fast overlapping optical pulses with precise delays is demonstrated in this work. Encoding events in this way potentially allows many detector channels to be simultaneously encoded onto a single optical fiber that is then read out by a single digitizer. A two channel silicon photomultiplier-based prototype utilizing this optical delay encoding technique along with dual threshold time-over-threshold is demonstrated.The optical encoding and multiplexing prototype achieves a coincidence time resolution of 160 ps full width at half maximum (FWHM) and an energy resolution of 13.1% FWHM at 511 keV with 3 × 3 × 5 mm(3) LYSO crystals. All interaction information for both detectors, including timing, energy, and channel identification, is encoded onto a single optical fiber with little degradation.Optical delay encoding and multiplexing technology could lead to time-of-flight PET scanners with fewer readout channels and simplified data acquisition systems.

View details for DOI 10.1118/1.4923176

View details for Web of Science ID 000358933000011

View details for PubMedID 26233181

View details for PubMedCentralID PMC4499043
Analytical calculation of the lower bound on timing resolution for PET scintillation detectors comprising high-aspect-ratio crystal elements PHYSICS IN MEDICINE AND BIOLOGY Cates, J. W., Vinke, R., Levin, C. S. 2015; 60 (13): 5141-5161
Abstract

Excellent timing resolution is required to enhance the signal-to-noise ratio (SNR) gain available from the incorporation of time-of-flight (ToF) information in image reconstruction for positron emission tomography (PET). As the detector's timing resolution improves, so does SNR, reconstructed image quality, and accuracy. This directly impacts the challenging detection and quantification tasks in the clinic. The recognition of these benefits has spurred efforts within the molecular imaging community to determine to what extent the timing resolution of scintillation detectors can be improved and develop near-term solutions for advancing ToF-PET. Presented in this work, is a method for calculating the Cramér-Rao lower bound (CRLB) on timing resolution for scintillation detectors with long crystal elements, where the influence of the variation in optical path length of scintillation light on achievable timing resolution is non-negligible. The presented formalism incorporates an accurate, analytical probability density function (PDF) of optical transit time within the crystal to obtain a purely mathematical expression of the CRLB with high-aspect-ratio (HAR) scintillation detectors. This approach enables the statistical limit on timing resolution performance to be analytically expressed for clinically-relevant PET scintillation detectors without requiring Monte Carlo simulation-generated photon transport time distributions. The analytically calculated optical transport PDF was compared with detailed light transport simulations, and excellent agreement was found between the two. The coincidence timing resolution (CTR) between two [Formula: see text] mm[Formula: see text] LYSO:Ce crystals coupled to analogue SiPMs was experimentally measured to be [Formula: see text] ps FWHM, approaching the analytically calculated lower bound within 6.5%.

View details for DOI 10.1088/0031-9155/60/13/5141

View details for Web of Science ID 000356872000014

View details for PubMedID 26083559
Shine-Through in PET/MR Imaging: Effects of the Magnetic Field on Positron Range and Subsequent Image Artifacts JOURNAL OF NUCLEAR MEDICINE Kolb, A., Sauter, A. W., Eriksson, L., Vandenbrouke, A., Liu, C. C., Levin, C., Pichler, B. J., Rafecas, M. 2015; 56 (6): 951-954
Abstract

Simultaneous PET/MR imaging is an emerging hybrid modality for clinical and preclinical imaging. The static magnetic field of the MR imaging device affects the trajectory of the positrons emitted by the PET radioisotopes. This effect translates into an improvement of the spatial resolution in transaxial images. However, because of the elongation of the positron range distribution along the magnetic field, the axial resolution worsens and shine-through artifacts may appear. These artifacts can lead to misinterpretation and overstaging. The aim of this work was to study the relevance of this effect.Measurements were performed in a 3-tesla PET/MR scanner. A 1-cm(2) piece of paper, soaked with a radioisotope and placed in air, was scanned, and the magnitude of the shine-through was quantified from the PET images for various radioisotopes. Additionally, PET/MR and PET/CT images of the lungs and the larynx with trachea of a deceased swine were obtained after injecting a mixture of NiSO4 and (68)Ga to simulate hot tumor lesions.For the radioactive paper, shine-through artifacts appeared in the location of the acrylic glass backplane, located 3 cm from the source in the axial direction. The ratio between the activity of the shine-through and the activity reconstructed in the original location ranged from 0.9 ((18)F) to 5.7 ((68)Ga). For the larynx-with-trachea images, the magnitude of the artifacts depended on the organ orientation with respect to the magnetic field. The shine-through activity could reach 46% of the reconstructed activity (larynx lesion). The lesion within the trachea produced 2 artifacts, symmetrically aligned with the magnetic field and characterized by artifact-to-lesion volume-of-interest ratios ranging from 21% to 30%.In simultaneous PET/MR imaging, the effect of the magnetic field on positrons may cause severe artifacts in the PET image when the lesions are close to air cavities and high-energy radioisotopes are used. For accurate staging and interpretation, this effect needs to be recognized and adequate compensation techniques should be developed.

View details for DOI 10.2967/jnumed.114.147637

View details for PubMedID 25766897
Direct conversion semiconductor detectors in positron emission tomography MODERN PHYSICS LETTERS A Cates, J. W., Gu, Y., Levin, C. S. 2015; 30 (14)
View details for DOI 10.1142/S0217732315300116

View details for Web of Science ID 000353297400001
Analog electro-optical readout of SiPMs achieves fast timing required for time-of-flight PET/MR PHYSICS IN MEDICINE AND BIOLOGY Bieniosek, M. F., Levin, C. S. 2015; 60 (9): 3795-3806
Abstract

The design of combined positron emission tomography/magnetic resonance (PET/MR) systems presents a number of challenges to engineers, as it forces the PET system to acquire data in a space constrained environment that is sensitive to electro-magnetic interference and contains high static, radio frequency and gradient fields. In this work we validate fast timing performance of a PET scintillation detector using a potentially very compact, very low power, and MR compatible readout method in which analog silicon photomultipliers (SiPM) signals are transmitted optically away from the MR bore with little or even no additional readout electronics. This analog 'electro-optial' method could reduce the entire PET readout in the MR bore to two compact, low power components (SiPMs and lasers). Our experiments show fast timing performance from analog electro-optical readout with and without pre-amplification. With 3 mm × 3 mm × 20 mm lutetium-yttrium oxyorthosilicate (LYSO) crystals and Excelitas SiPMs the best two-sided fwhm coincident timing resolution achieved was 220 +/- 3 ps in electrical mode, 230 +/- 2 ps in electro-optical with preamp mode, and 253 +/- 2 ps in electro-optical without preamp mode. Timing measurements were also performed with Hamamatsu SiPMs and 3 mm × 3 mm × 5 mm crystals. In the future the timing degradation seen can be further reduced with lower laser noise or improvements SiPM rise time or gain.

View details for DOI 10.1088/0031-9155/60/9/3795

View details for Web of Science ID 000354104700026

View details for PubMedID 25905626

View details for PubMedCentralID PMC4431650
Prototype positron emission tomography insert with electro-optical signal transmission for simultaneous operation with MRI PHYSICS IN MEDICINE AND BIOLOGY Olcott, P., Kim, E., Hong, K., Lee, B. J., Grant, A. M., Chang, C., Glover, G., Levin, C. S. 2015; 60 (9): 3459-3478
Abstract

The simultaneous acquisition of PET and MRI data shows promise to provide powerful capabilities to study disease processes in human subjects, guide the development of novel treatments, and monitor therapy response and disease progression. A brain-size PET detector ring insert for an MRI system is being developed that, if successful, can be inserted into any existing MRI system to enable simultaneous PET and MRI images of the brain to be acquired without mutual interference. The PET insert uses electro-optical coupling to relay all the signals from the PET detectors out of the MRI system using analog modulated lasers coupled to fiber optics. Because the fibers use light instead of electrical signals, the PET detector can be electrically decoupled from the MRI making it partially transmissive to the RF field of the MRI. The SiPM devices and low power lasers were powered using non-magnetic MRI compatible batteries. Also, the number of laser-fiber channels in the system was reduced using techniques adapted from the field of compressed sensing. Using the fact that incoming PET data is sparse in time and space, electronic circuits implementing constant weight codes uniquely encode the detector signals in order to reduce the number of electro-optical readout channels by 8-fold. Two out of a total of sixteen electro-optical detector modules have been built and tested with the entire RF-shielded detector gantry for the PET ring insert. The two detectors have been tested outside and inside of a 3T MRI system to study mutual interference effects and simultaneous performance with MRI. Preliminary results show that the PET insert is feasible for high resolution simultaneous PET/MRI imaging for applications in the brain.

View details for DOI 10.1088/0031-9155/60/9/3459

View details for Web of Science ID 000354104700007

View details for PubMedID 25856511
Electrical delay line multiplexing for pulsed mode radiation detectors PHYSICS IN MEDICINE AND BIOLOGY Vinke, R., Yeom, J. Y., Levin, C. S. 2015; 60 (7): 2785-2802
Abstract

Medical imaging systems are composed of a large number of position sensitive radiation detectors to provide high resolution imaging. For example, whole-body Positron Emission Tomography (PET) systems are typically composed of thousands of scintillation crystal elements, which are coupled to photosensors. Thus, PET systems greatly benefit from methods to reduce the number of data acquisition channels, in order to reduce the system development cost and complexity. In this paper we present an electrical delay line multiplexing scheme that can significantly reduce the number of readout channels, while preserving the signal integrity required for good time resolution performance. We experimented with two 4 × 4 LYSO crystal arrays, with crystal elements having 3 mm × 3 mm × 5 mm and 3 mm × 3 mm × 20 mm dimensions, coupled to 16 Hamamatsu MPPC S10931-050P SiPM elements. Results show that each crystal could be accurately identified, even in the presence of scintillation light sharing and inter-crystal Compton scatter among neighboring crystal elements. The multiplexing configuration degraded the coincidence timing resolution from ∼243 ps FWHM to ∼272 ps FWHM when 16 SiPM signals were combined into a single channel for the 4 × 4 LYSO crystal array with 3 mm × 3 mm × 20 mm crystal element dimensions, in coincidence with a 3 mm × 3 mm × 5 mm LYSO crystal pixel. The method is flexible to allow multiplexing configurations across different block detectors, and is scalable to an entire ring of detectors.

View details for DOI 10.1088/0031-9155/60/7/2785

View details for Web of Science ID 000352516000013

View details for PubMedID 25768002

View details for PubMedCentralID PMC4386692
Simultaneous Whole-Body Time-of-Flight F-18-FDG PET/MRI A Pilot Study Comparing SUVmax With PET/CT and Assessment of MR Image Quality CLINICAL NUCLEAR MEDICINE Iagaru, A., Mittra, E., Minamimoto, R., Jamali, M., Levin, C., Quon, A., Gold, G., Herfkens, R., Vasanawala, S., Gambhir, S. S., Zaharchuk, G. 2015; 14 (1): 1-8
Abstract

The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF.We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality.Thirty-six patients (19 men, 17 women, mean [±standard deviation] age of 61 ± 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (±standard deviation) of 74 ± 14 minutes (range: 49-100 minutes) after injection of 10 ± 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 ± 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed.The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

View details for Web of Science ID 000346633400023
Simultaneous whole-body time-of-flight 18F-FDG PET/MRI: a pilot study comparing SUVmax with PET/CT and assessment of MR image quality. Clinical nuclear medicine Iagaru, A., Mittra, E., Minamimoto, R., Jamali, M., Levin, C., Quon, A., Gold, G., Herfkens, R., Vasanawala, S., Gambhir, S. S., Zaharchuk, G. 2015; 40 (1): 1-8
Abstract

The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF.We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality.Thirty-six patients (19 men, 17 women, mean [±standard deviation] age of 61 ± 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (±standard deviation) of 74 ± 14 minutes (range: 49-100 minutes) after injection of 10 ± 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 ± 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed.The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

View details for DOI 10.1097/RLU.0000000000000611

View details for PubMedID 25489952
Thermal regulation of tightly packed solid-state photodetectors in a 1 mm(3) resolution clinical PET system. Medical physics Freese, D. L., Vandenbroucke, A., Innes, D., Lau, F. W., Hsu, D. F., Reynolds, P. D., Levin, C. S. 2015; 42 (1): 305-?
Abstract

Silicon photodetectors are of significant interest for use in positron emission tomography (PET) systems due to their compact size, insensitivity to magnetic fields, and high quantum efficiency. However, one of their main disadvantages is fluctuations in temperature cause strong shifts in gain of the devices. PET system designs with high photodetector density suffer both increased thermal density and constrained options for thermally regulating the devices. This paper proposes a method of thermally regulating densely packed silicon photodetectors in the context of a 1 mm(3) resolution, high-sensitivity PET camera dedicated to breast imaging.The PET camera under construction consists of 2304 units, each containing two 8 × 8 arrays of 1 mm(3) LYSO crystals coupled to two position sensitive avalanche photodiodes (PSAPD). A subsection of the proposed camera with 512 PSAPDs has been constructed. The proposed thermal regulation design uses water-cooled heat sinks, thermoelectric elements, and thermistors to measure and regulate the temperature of the PSAPDs in a novel manner. Active cooling elements, placed at the edge of the detector stack due to limited access, are controlled based on collective leakage current and temperature measurements in order to keep all the PSAPDs at a consistent temperature. This thermal regulation design is characterized for the temperature profile across the camera and for the time required for cooling changes to propagate across the camera. These properties guide the implementation of a software-based, cascaded proportional-integral-derivative control loop that controls the current through the Peltier elements by monitoring thermistor temperature and leakage current. The stability of leakage current, temperature within the system using this control loop is tested over a period of 14 h. The energy resolution is then measured over a period of 8.66 h. Finally, the consistency of PSAPD gain between independent operations of the camera over 10 days is tested.The PET camera maintains a temperature of 18.00 ± 0.05 °C over the course of 12 h while the ambient temperature varied 0.61 °C, from 22.83 to 23.44 °C. The 511 keV photopeak energy resolution over a period of 8.66 h is measured to be 11.3% FWHM with a maximum photopeak fluctuation of 4 keV. Between measurements of PSAPD gain separated by at least 2 day, the maximum photopeak shift was 6 keV.The proposed thermal regulation scheme for tightly packed silicon photodetectors provides for stable operation of the constructed subsection of a PET camera over long durations of time. The energy resolution of the system is not degraded despite shifts in ambient temperature and photodetector heat generation. The thermal regulation scheme also provides a consistent operating environment between separate runs of the camera over different days. Inter-run consistency allows for reuse of system calibration parameters from study to study, reducing the time required to calibrate the system and hence to obtain a reconstructed image.

View details for DOI 10.1118/1.4903889

View details for PubMedID 25563270

View details for PubMedCentralID PMC4277559
Side readout of long scintillation crystal elements with digital SiPM for TOF-DOI PET MEDICAL PHYSICS Yeom, J. Y., Vinke, R., Levin, C. S. 2014; 41 (12)
Abstract

Side readout of scintillation light from crystal elements in positron emission tomography (PET) is an alternative to conventional end-readout configurations, with the benefit of being able to provide accurate depth-of-interaction (DOI) information and good energy resolution while achieving excellent timing resolution required for time-of-flight PET. This paper explores different readout geometries of scintillation crystal elements with the goal of achieving a detector that simultaneously achieves excellent timing resolution, energy resolution, spatial resolution, and photon sensitivity.The performance of discrete LYSO scintillation elements of different lengths read out from the end/side with digital silicon photomultipliers (dSiPMs) has been assessed.Compared to 3 × 3 × 20 mm(3) LYSO crystals read out from their ends with a coincidence resolving time (CRT) of 162 ± 6 ps FWHM and saturated energy spectra, a side-readout configuration achieved an excellent CRT of 144 ± 2 ps FWHM after correcting for timing skews within the dSiPM and an energy resolution of 11.8% ± 0.2% without requiring energy saturation correction. Using a maximum likelihood estimation method on individual dSiPM pixel response that corresponds to different 511 keV photon interaction positions, the DOI resolution of this 3 × 3 × 20 mm(3) crystal side-readout configuration was computed to be 0.8 mm FWHM with negligible artifacts at the crystal ends. On the other hand, with smaller 3 × 3 × 5 mm(3) LYSO crystals that can also be tiled/stacked to provide DOI information, a timing resolution of 134 ± 6 ps was attained but produced highly saturated energy spectra.The energy, timing, and DOI resolution information extracted from the side of long scintillation crystal elements coupled to dSiPM have been acquired for the first time. The authors conclude in this proof of concept study that such detector configuration has the potential to enable outstanding detector performance in terms of timing, energy, and DOI resolution.

View details for DOI 10.1118/1.4901524

View details for Web of Science ID 000346176300035

View details for PubMedID 25471979

View details for PubMedCentralID PMC4247369
The lower timing resolution bound for scintillators with non-negligible optical photon transport time in time-of-flight PET PHYSICS IN MEDICINE AND BIOLOGY Vinke, R., Olcott, P. D., Cates, J. W., Levin, C. S. 2014; 59 (20): 6215-6229
View details for DOI 10.1088/0031-9155/59/20/6215

View details for Web of Science ID 000343092300016
The lower timing resolution bound for scintillators with non-negligible optical photon transport time in time-of-flight PET. Physics in medicine and biology Vinke, R., Olcott, P. D., Cates, J. W., Levin, C. S. 2014; 59 (20): 6215-6229
Abstract

In this work, a method is presented that can calculate the lower bound of the timing resolution for large scintillation crystals with non-negligible photon transport. Hereby, the timing resolution bound can directly be calculated from Monte Carlo generated arrival times of the scintillation photons. This method extends timing resolution bound calculations based on analytical equations, as crystal geometries can be evaluated that do not have closed form solutions of arrival time distributions. The timing resolution bounds are calculated for an exemplary 3 mm × 3 mm × 20 mm LYSO crystal geometry, with scintillation centers exponentially spread along the crystal length as well as with scintillation centers at fixed distances from the photosensor. Pulse shape simulations further show that analog photosensors intrinsically operate near the timing resolution bound, which can be attributed to the finite single photoelectron pulse rise time.

View details for DOI 10.1088/0031-9155/59/20/6215

View details for PubMedID 25255807

View details for PubMedCentralID PMC4216231
Thermal regulation for APDs in a 1 mm(3) resolution clinical PET camera: design, simulation and experimental verification PHYSICS IN MEDICINE AND BIOLOGY Zhai, J., Vandenbroucke, A., Levin, C. S. 2014; 59 (14): 3951-3967
View details for DOI 10.1088/0031-9155/59/14/3951

View details for Web of Science ID 000338771300018
Thermal regulation for APDs in a 1?mm(3) resolution clinical PET camera: design, simulation and experimental verification. Physics in medicine and biology Zhai, J., Vandenbroucke, A., Levin, C. S. 2014; 59 (14): 3951-3967
Abstract

We are developing a 1 mm(3) resolution positron emission tomography camera dedicated to breast imaging. The camera collects high energy photons emitted from radioactively labeled agents introduced in the patients in order to detect molecular signatures of breast cancer. The camera comprises many layers of lutetium yttrium oxyorthosilicate (LYSO) scintillation crystals coupled to position sensitive avalanche photodiodes (PSAPDs). The main objectives of the studies presented in this paper are to investigate the temperature profile of the layers of LYSO-PSAPD detectors (a.k.a. 'fins') residing in the camera and to use these results to present the design of the thermal regulation system for the front end of the camera. The study was performed using both experimental methods and simulation. We investigated a design with a heat-dissipating fin. Three fin configurations are tested: fin with Al windows (FwW), fin without Al windows (FwoW) and fin with alumina windows (FwAW). A Fluent® simulation was conducted to study the experimentally inaccessible temperature of the PSAPDs. For the best configuration (FwW), the temperature difference from the center to a point near the edge is 1.0 K when 1.5 A current was applied to the Peltier elements. Those of FwoW and FwAW are 2.6 K and 1.7 K, respectively. We conclude that the design of a heat-dissipating fin configuration with 'aluminum windows' (FwW) that borders the scintillation crystal arrays of 16 adjacent detector modules has better heat dissipation capabilities than the design without 'aluminum windows' (FwoW) and the design with 'alumina windows' (FwAW), respectively.

View details for DOI 10.1088/0031-9155/59/14/3951

View details for PubMedID 24971652
A new dual threshold time-over-threshold circuit for fast timing in PET PHYSICS IN MEDICINE AND BIOLOGY Grant, A. M., Levin, C. S. 2014; 59 (13): 3421-3430
Abstract

Time-over-threshold (ToT) is attractive as a method of combined timing and energy encoding in positron emission tomography (PET) due to its simplicity in implementation and readout. However, conventional single threshold ToT has a nonlinear response and generally suffers from a tradeoff between timing and energy resolution. The resulting poor performance is not fit for applications requiring fast timing, such as time-of-flight (ToF) PET. In this work it is shown experimentally that by replacing single threshold ToT with a dual threshold method in a new compact circuit, excellent time resolution can be achieved (154 ps FWHM for 3 × 3 × 5 mm(3) LYSO crystals), suitable for ToF. Dual threshold ToT timing results have been compared to a similar single threshold design, demonstrating that dual threshold ToT performance is far superior to that of single threshold ToT (154 ps versus 418 ps coincidence time resolution for the dual and single threshold cases, respectively). A method of correcting for nonlinearity in dual threshold ToT energy spectra is also demonstrated.

View details for DOI 10.1088/0031-9155/59/13/3421

View details for Web of Science ID 000338424800014

View details for PubMedID 24889105
RF-Penetrable PET insert for simultaneous PET/MR imaging. EJNMMI physics Lee, B. J., Grant, A. M., Chang, C., Levin, C. S. 2014; 1: A5-?
View details for DOI 10.1186/2197-7364-1-S1-A5

View details for PubMedID 26501638

View details for PubMedCentralID PMC4545802
Analog electro-optical readout of SiPMs for compact, low power ToF PET/MRI. EJNMMI physics Bieniosek, M. F., Levin, C. S. 2014; 1: A12-?
View details for DOI 10.1186/2197-7364-1-S1-A12

View details for PubMedID 26501597

View details for PubMedCentralID PMC4545846
Performance of a high sensitivity time-of-flight PET ring operating simultaneously within a 3T MR system. EJNMMI physics Levin, C. S., Jansen, F., Deller, T., Maramraju, S. H., Grant, A., Iagaru, A. 2014; 1: A72-?
View details for DOI 10.1186/2197-7364-1-S1-A72

View details for PubMedID 26501663

View details for PubMedCentralID PMC4545961
A method to achieve spatial linearity and uniform resolution at the edges of monolithic scintillation crystal detectors PHYSICS IN MEDICINE AND BIOLOGY Vinke, R., Levin, C. S. 2014; 59 (12): 2975-2995
Abstract

We have performed Monte Carlo simulations of the scintillation light transport between adjacent monolithic LYSO crystals that are optically coupled together using coupling media of varying refractive index. The scintillation light from the crystals was read out by SiPM arrays from the large crystal face. Scintillation event positioning results show that this optical coupling technique preserves the shape of the light spread function near and across the interface between the two crystals in order to substantially reduce the edge-artifacts observed in monolithic scintillation crystals, while not degrading the timing performance.

View details for DOI 10.1088/0031-9155/59/12/2975

View details for Web of Science ID 000337176600008

View details for PubMedID 24841984
Study of electrode pattern design for a CZT-based PET detector PHYSICS IN MEDICINE AND BIOLOGY Gu, Y., Levin, C. S. 2014; 59 (11): 2599-2621
Abstract

We are developing a 1 mm resolution small animal positron emission tomography (PET) system using 3D positioning cadmium zinc telluride photon detectors comprising 40 mm × 40 mm × 5 mm crystals metalized with a cross-strip electrode pattern with a 1 mm anode strip pitch. We optimized the electrode pattern design for intrinsic sensitivity and spatial, energy and time resolution performance using a test detector comprising cathode and steering electrode strips of varying dimensions. The study found 3 and 5 mm width cathode strips locate charge-shared photon interactions near cathode strip boundaries with equal precision. 3 mm width cathode strips exhibited large time resolution variability as a function of photon interaction location between the anode and cathode planes (~26 to ~127.5 ns full width at half maximum (FWHM) for 0.5 mm and 4.2 mm depths, respectively). 5 mm width cathode strips by contrast exhibited more stable time resolution for the same interaction locations (~34 to ~83 ns FWHM), provided more linear spatial positioning in the direction orthogonal to the electrode planes, and as much as 68.4% improvement in photon sensitivity over the 3 mm wide cathode strips. The results were understood by analyzing the cathode strips' weighting functions, which indicated a stronger 'small pixel' effect in the 3 mm wide cathode strips. Photon sensitivity and anode energy resolution were seen to improve with decreasing steering electrode bias from 0 to -80 V w.r.t. the anode potential. A slight improvement in energy resolution was seen for wider steering electrode strips (400 versus 100 µm) for charge-shared photon interactions. Although this study successfully focused on electrode pattern features for PET performance, the results are generally applicable to semiconductor photon detectors employing cross-trip electrode patterns.

View details for DOI 10.1088/0031-9155/59/11/2599

View details for Web of Science ID 000336459000005

View details for PubMedID 24786208

View details for PubMedCentralID PMC4065862
Clinical evaluation of a novel intraoperative handheld gamma camera for sentinel lymph node biopsy. Physica medica Olcott, P., Pratx, G., Johnson, D., Mittra, E., Niederkohr, R., Levin, C. S. 2014; 30 (3): 340-345
Abstract

Preoperative lymphoscintigraphy (PLS) combined with intraoperative gamma probe (GP) localization is standard procedure for localizing the sentinel lymph nodes (SLN) in melanoma and breast cancer. In this study, we evaluated the ability of a novel intraoperative handheld gamma camera (IHGC) to image SLNs during surgery.The IHGC is a small-field-of-view camera optimized for real-time imaging of lymphatic drainage patterns. Unlike conventional cameras, the IHGC can acquire useful images in a few seconds in a free-running fashion and be moved manually around the patient to find a suitable view of the node. Thirty-nine melanoma and eleven breast cancer patients underwent a modified SLN biopsy protocol in which nodes localized with the GP were imaged with the IHGC. The IHGC was also used to localize additional nodes that could not be found with the GP.The removal of 104 radioactive SLNs was confirmed ex vivo by GP counting. In vivo, the relative node detection sensitivity was 88.5 (82.3, 94.6)% for the IHGC (used in conjunction with the GP) and 94.2 (89.7, 98.7)% for the GP alone, a difference not found to be statistically significant (McNemar test, p = 0.24).Small radioactive SLNs can be visualized intraoperatively using the IHGC with exposure time of 20 s or less, with no significant difference in node detection sensitivity compared to a GP. The IHGC is a useful complement to the GP, especially for SLNs that are difficult to locate with the GP alone.

View details for DOI 10.1016/j.ejmp.2013.10.005

View details for PubMedID 24239343
Development of an Ultrahigh Resolution Block Detector Based on 0.4 mm Pixel Ce:GAGG Scintillators and a Silicon Photomultiplier Array IEEE TRANSACTIONS ON NUCLEAR SCIENCE Yamamoto, S., Yeom, J. Y., Kamada, K., Endo, T., Levin, C. S. 2013; 60 (6): 4582-4587
View details for DOI 10.1109/TNS.2013.2282294

View details for Web of Science ID 000328971500001
Readout strategy of an electro-optical coupled PET detector for time-of-flight PET/MRI PHYSICS IN MEDICINE AND BIOLOGY Bieniosek, M. F., Olcott, P. D., Levin, C. S. 2013; 58 (20): 7227-7238
Abstract

Combining PET with MRI in a single system provides clinicians with complementary molecular and anatomical information. However, existing integrated PET/MRI systems do not have time-of-flight (ToF) PET capabilities. This work describes an MRI-compatible front-end electronic system with ToF capabilities. The approach employs a fast arrival-time pickoff comparator to digitize the timing information, and a laser diode to drive a 10 m fiber-optic cable to optically transmit asynchronous timing information to a photodiode receiver readout system. The FWHM jitter of the comparator and this electo-optical link is 11.5 ps in response to a fast digital pulse. When configured with LYSO scintillation crystals and Hamamatsu MPPC silicon photo-multipliers the comparator and electro-optical link achieved a 511 keV coincidence time resolution of 254.7 ps +/- 8.0 ps FWHM with 3 × 3 × 20 mm(3) crystals and 166.5 +/- 2.5 ps FWHM with 3 × 3 × 5 mm(3) crystals.

View details for DOI 10.1088/0031-9155/58/20/7227

View details for Web of Science ID 000325172500013

View details for PubMedID 24061218
Readout strategy of an electro-optical coupled PET detector for time-of-flight PET/MRI. Physics in medicine and biology Bieniosek, M. F., Olcott, P. D., Levin, C. S. 2013; 58 (20): 7227-7238
Abstract

Combining PET with MRI in a single system provides clinicians with complementary molecular and anatomical information. However, existing integrated PET/MRI systems do not have time-of-flight (ToF) PET capabilities. This work describes an MRI-compatible front-end electronic system with ToF capabilities. The approach employs a fast arrival-time pickoff comparator to digitize the timing information, and a laser diode to drive a 10 m fiber-optic cable to optically transmit asynchronous timing information to a photodiode receiver readout system. The FWHM jitter of the comparator and this electo-optical link is 11.5 ps in response to a fast digital pulse. When configured with LYSO scintillation crystals and Hamamatsu MPPC silicon photo-multipliers the comparator and electro-optical link achieved a 511 keV coincidence time resolution of 254.7 ps +/- 8.0 ps FWHM with 3 × 3 × 20 mm(3) crystals and 166.5 +/- 2.5 ps FWHM with 3 × 3 × 5 mm(3) crystals.

View details for DOI 10.1088/0031-9155/58/20/7227

View details for PubMedID 24061218
Readout Electronics and Data Acquisition of a Positron Emission Tomography Time-of-Flight Detector Module With Waveform Digitizer IEEE TRANSACTIONS ON NUCLEAR SCIENCE Yeom, J. Y., Vinke, R., Spanoudaki, V. C., Hong, K. J., Levin, C. S. 2013; 60 (5): 3735-3741
View details for DOI 10.1109/TNS.2013.2264947

View details for Web of Science ID 000325827700049
Trends of Data Path Topologies for Data Acquisition Systems in Positron Emission Tomography IEEE TRANSACTIONS ON NUCLEAR SCIENCE Kim, E., Hong, K. J., Yeom, J. Y., Olcott, P. D., Levin, C. S. 2013; 60 (5): 3746-3757
View details for DOI 10.1109/TNS.2013.2281419

View details for Web of Science ID 000325827700051
Cross-Strip Multiplexed Electro-Optical Coupled Scintillation Detector for Integrated PET/MRI IEEE TRANSACTIONS ON NUCLEAR SCIENCE Olcott, P. D., Glover, G., Levin, C. S. 2013; 60 (5): 3198-3204
View details for DOI 10.1109/TNS.2013.2271916

View details for Web of Science ID 000325827200005
Compact pulse width modulation circuitry for silicon photomultiplier readout. Physics in medicine and biology Bieniosek, M. F., Olcott, P. D., Levin, C. S. 2013; 58 (15): 5049-5059
Abstract

The adoption of solid-state photodetectors for positron emission tomography (PET) system design and the interest in 3D interaction information from PET detectors has lead to an increasing number of readout channels in PET systems. To handle these additional readout channels, PET readout electronics should be simplified to reduce the power consumption, cost, and size of the electronics for a single channel. Pulse-width modulation (PWM), where detector pulses are converted to digital pulses with width proportional to the detected photon energy, promises to simplify PET readout by converting the signals to digital form at the beginning of the processing chain, and allowing a single time-to-digital converter to perform the data acquisition for many channels rather than routing many analogue channels and digitizing in the back end. Integrator based PWM systems, also known as charge-to-time converters (QTCs), are especially compact, reducing the front-end electronics to an op-amp integrator with a resistor discharge, and a comparator. QTCs, however, have a long dead-time during which dark count noise is integrated, reducing the output signal-to-noise ratio. This work presents a QTC based PWM circuit with a gated integrator that shows performance improvements over existing QTC based PWM. By opening and closing an analogue switch on the input of the integrator, the circuit can be controlled to integrate only the portions of the signal with a high signal-to-noise ratio. It also allows for multiplexing different detectors into the same PWM circuit while avoiding uncorrelated noise propagation between photodetector channels. Four gated integrator PWM circuits were built to readout the spatial channels of two position sensitive solid-state photomultiplier (PS-SSPM). Results show a 4 × 4 array 0.9 mm × 0.9 mm × 15 mm of LYSO crystals being identified on the 5 mm × 5 mm PS-SSPM at room temperature with no degradation for twofold multiplexing. In principle, much larger multiplexing ratios are possible, limited only by count rate issues.

View details for DOI 10.1088/0031-9155/58/15/5049

View details for PubMedID 23831601
Compact pulse width modulation circuitry for silicon photomultiplier readout PHYSICS IN MEDICINE AND BIOLOGY Bieniosek, M. F., Olcott, P. D., Levin, C. S. 2013; 58 (15)
View details for DOI 10.1088/0031-9155/58/15/5049

View details for Web of Science ID 000322028000006

View details for PubMedID 23831601
Single-photon sampling architecture for solid-state imaging sensors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Van Den Berg, E., Candes, E., Chinn, G., Levin, C., Olcott, P. D., Sing-Long, C. 2013; 110 (30): E2752-E2761
Abstract

Advances in solid-state technology have enabled the development of silicon photomultiplier sensor arrays capable of sensing individual photons. Combined with high-frequency time-to-digital converters (TDCs), this technology opens up the prospect of sensors capable of recording with high accuracy both the time and location of each detected photon. Such a capability could lead to significant improvements in imaging accuracy, especially for applications operating with low photon fluxes such as light detection and ranging and positron-emission tomography. The demands placed on on-chip readout circuitry impose stringent trade-offs between fill factor and spatiotemporal resolution, causing many contemporary designs to severely underuse the technology's full potential. Concentrating on the low photon flux setting, this paper leverages results from group testing and proposes an architecture for a highly efficient readout of pixels using only a small number of TDCs. We provide optimized design instances for various sensor parameters and compute explicit upper and lower bounds on the number of TDCs required to uniquely decode a given maximum number of simultaneous photon arrivals. To illustrate the strength of the proposed architecture, we note a typical digitization of a 60 × 60 photodiode sensor using only 142 TDCs. The design guarantees registration and unique recovery of up to four simultaneous photon arrivals using a fast decoding algorithm. By contrast, a cross-strip design requires 120 TDCs and cannot uniquely decode any simultaneous photon arrivals. Among other realistic simulations of scintillation events in clinical positron-emission tomography, the above design is shown to recover the spatiotemporal location of 99.98% of all detected photons.

View details for DOI 10.1073/pnas.1216318110

View details for Web of Science ID 000322112300005

View details for PubMedID 23836643
Fast Timing Silicon Photomultipliers for Scintillation Detectors IEEE PHOTONICS TECHNOLOGY LETTERS Yeom, J. Y., Vinke, R., Pavlov, N., Bellis, S., Wall, L., O'Neill, K., Jackson, C., Levin, C. S. 2013; 25 (14): 1309-1312
View details for DOI 10.1109/LPT.2013.2264049

View details for Web of Science ID 000321151600003
Sparse Signal Recovery Methods for Multiplexing PET Detector Readout IEEE TRANSACTIONS ON MEDICAL IMAGING Chinn, G., Olcott, P. D., Levin, C. S. 2013; 32 (5): 932-942
Abstract

Nuclear medicine imaging detectors are commonly multiplexed to reduce the number of readout channels. Because the underlying detector signals have a sparse representation, sparse recovery methods such as compressed sensing may be used to develop new multiplexing schemes. Random methods may be used to create sensing matrices that satisfy the restricted isometry property. However, the restricted isometry property provides little guidance for developing multiplexing networks with good signal-to-noise recovery capability. In this work, we describe compressed sensing using a maximum likelihood framework and develop a new method for constructing multiplexing (sensing) matrices that can recover signals more accurately in a mean square error sense compared to sensing matrices constructed by random construction methods. Signals can then be recovered by maximum likelihood estimation constrained to the support recovered by either greedy l₀ iterative algorithms or l₁-norm minimization techniques. We show that this new method for constructing and decoding sensing matrices recovers signals with 4%-110% higher SNR than random Gaussian sensing matrices, up to 100% higher SNR than partial DCT sensing matrices 50%-2400% higher SNR than cross-strip multiplexing, and 22%-210% higher SNR than Anger multiplexing for photoelectric events.

View details for DOI 10.1109/TMI.2013.2246182

View details for Web of Science ID 000318643500009

View details for PubMedID 23475349
Distributed MLEM: An Iterative Tomographic Image Reconstruction Algorithm for Distributed Memory Architectures IEEE TRANSACTIONS ON MEDICAL IMAGING Cui, J., Pratx, G., Meng, B., Levin, C. S. 2013; 32 (5): 957-967
Abstract

The processing speed for positron emission tomography (PET) image reconstruction has been greatly improved in recent years by simply dividing the workload to multiple processors of a graphics processing unit (GPU). However, if this strategy is generalized to a multi-GPU cluster, the processing speed does not improve linearly with the number of GPUs. This is because large data transfer is required between the GPUs after each iteration, effectively reducing the parallelism. This paper proposes a novel approach to reformulate the maximum likelihood expectation maximization (MLEM) algorithm so that it can scale up to many GPU nodes with less frequent inter-node communication. While being mathematically different, the new algorithm maximizes the same convex likelihood function as MLEM, thus converges to the same solution. Experiments on a multi-GPU cluster demonstrate the effectiveness of the proposed approach.

View details for DOI 10.1109/TMI.2013.2252913

View details for Web of Science ID 000318643500011

View details for PubMedID 23529079
First Performance Results of Ce:GAGG Scintillation Crystals With Silicon Photomultipliers Symposium on Radiation Measurements and Applications (SORMA) Yeom, J. Y., Yamamoto, S., Derenzo, S. E., Spanoudaki, V. C., Kamada, K., Endo, T., Levin, C. S. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2013: 988–92
View details for DOI 10.1109/TNS.2012.2233497

View details for Web of Science ID 000320856500088
Optimizing timing performance of silicon photomultiplier-based scintillation detectors PHYSICS IN MEDICINE AND BIOLOGY Yeom, J. Y., Vinke, R., Levin, C. S. 2013; 58 (4): 1207-1220
Abstract

Precise timing resolution is crucial for applications requiring photon time-of-flight (ToF) information such as ToF positron emission tomography (PET). Silicon photomultipliers (SiPM) for PET, with their high output capacitance, are known to require custom preamplifiers to optimize timing performance. In this paper, we describe simple alternative front-end electronics based on a commercial low-noise RF preamplifier and methods that have been implemented to achieve excellent timing resolution. Two radiation detectors with L(Y)SO scintillators coupled to Hamamatsu SiPMs (MPPC S10362-33-050C) and front-end electronics based on an RF amplifier (MAR-3SM+), typically used for wireless applications that require minimal additional circuitry, have been fabricated. These detectors were used to detect annihilation photons from a Ge-68 source and the output signals were subsequently digitized by a high speed oscilloscope for offline processing. A coincident resolving time (CRT) of 147 ± 3 ps FWHM and 186 ± 3 ps FWHM with 3 × 3 × 5 mm(3) and with 3 × 3 × 20 mm(3) LYSO crystal elements were measured, respectively. With smaller 2 × 2 × 3 mm(3) LSO crystals, a CRT of 125 ± 2 ps FWHM was achieved with slight improvement to 121 ± 3 ps at a lower temperature (15° C). Finally, with the 20 mm length crystals, a degradation of timing resolution was observed for annihilation photon interactions that occur close to the photosensor compared to shallow depth-of-interaction (DOI). We conclude that commercial RF amplifiers optimized for noise, besides their ease of use, can produce excellent timing resolution comparable to best reported values acquired with custom readout electronics. On the other hand, as timing performance degrades with increasing photon DOI, a head-on detector configuration will produce better CRT than a side-irradiated setup for longer crystals.

View details for DOI 10.1088/0031-9155/58/4/1207

View details for Web of Science ID 000314396800029

View details for PubMedID 23369872

View details for PubMedCentralID PMC3675904
In situ study of the impact of inter- and intra-reader variability on region of interest (ROI) analysis in preclinical molecular imaging. American journal of nuclear medicine and molecular imaging Habte, F., Budhiraja, S., Keren, S., Doyle, T. C., Levin, C. S., Paik, D. S. 2013; 3 (2): 175-181
Abstract

We estimated reader-dependent variability of region of interest (ROI) analysis and evaluated its impact on preclinical quantitative molecular imaging. To estimate reader variability, we used five independent image datasets acquired each using microPET and multispectral fluorescence imaging (MSFI). We also selected ten experienced researchers who utilize molecular imaging in the same environment that they typically perform their own studies. Nine investigators blinded to the data type completed the ROI analysis by drawing ROIs manually that delineate the tumor regions to the best of their knowledge and repeated the measurements three times, non-consecutively. Extracted mean intensities of voxels within each ROI are used to compute the coefficient of variation (CV) and characterize the inter- and intra-reader variability. The impact of variability was assessed through random samples iterated from normal distributions for control and experimental groups on hypothesis testing and computing statistical power by varying subject size, measured difference between groups and CV. The results indicate that inter-reader variability was 22.5% for microPET and 72.2% for MSFI. Additionally, mean intra-reader variability was 10.1% for microPET and 26.4% for MSFI. Repeated statistical testing showed that a total variability of CV < 50% may be needed to detect differences < 50% between experimental and control groups when six subjects (n = 6) or more are used and statistical power is adequate (80%). Surprisingly high variability has been observed mainly due to differences in the ROI placement and geometry drawn between readers, which may adversely affect statistical power and erroneously lead to negative study outcomes.

View details for PubMedID 23526701
An MLEM Method for Joint Tissue Activity Distribution and Photon Attenuation Map Reconstruction in PET 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Mihlin, A., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163500025
A 16-Channel FPGA-Based Time-to-Digital Converter for Pulse Width Modulation Circuitry for Silicon Photomultiplier Readout 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Hong, K. J., Bieniosek, M. F., Kim, E., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163501012
Novel Photon-Counting Energy-Resolving Ultra-Fast X-Ray Detector 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Ertosun, M. G., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163500013
Scintillation Crystal Side-Readout with SiPMs for Improved Time Resolution 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Bieniosek, M. F., Yeom, J. Y., Alvarez, L. C., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163500070
Optical Encoding and Multiplexing of Detector Signals with Dual Threshold Time-over-Threshold 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Grant, A. M., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163501008
Studies of Electromagnetic Interference of PET Detector Insert for Simultaneous PET/MRI 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Lee, B. J., Olcott, P. D., Hong, K. J., Grant, A. M., Chang, C., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163500037
Electrical delay line multiplexing for pulsed mode radiation detectors 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Vinke, R., Yeom, J. Y., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163500008
First measurements of a 512 PSAPD prototype of a sub-mm resolution clinical PET camera 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Vandenbroucke, A., Reynolds, P. D., Lau, F. W., INNES, D. R., Freese, D. L., Hsu, D. F., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163501220
Characterization of PET Data Acquisition System with Compressed Sensing Detectors 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Chang, C., Olcott, P. D., Hong, K. J., Grant, A. M., Lee, B. J., Kim, E., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163501024
General spatial distortion correction method for solid-state position sensitive detectors in PET 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Cui, S., Vandenbroucke, A., Bieniosek, M., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163500021
A Pulse Width Modulation Readout Method for Densely Packed Solid State Photodetectors 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Bieniosek, M. F., Hong, K. J., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163501009
3D Printing for Cost-Effective, Customized, Reusable Multi-Modality Imaging Phantoms 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Bieniosek, M. F., Lee, B. J., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163501001
Analyzing the Stability of 256 APDs Through Leakage Current and Temperature Monitoring in a 1 mm(3) Resolution Clinical PET System 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Freese, D. L., Vandenbroucke, A., Innes, D., Lau, F. W., Hsu, D. F., Reynolds, P. D., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163500072
Comparison of End/Side Scintillator Readout with Digital-SiPM for ToF PET 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Yeom, J. Y., Vinke, R., Bieniosek, M. F., Levin, C. S. IEEE. 2013
View details for Web of Science ID 000347163501136
Signal Conditioning Technique for Position Sensitive Photodetectors to Manipulate Pixelated Crystal Identification Capabilities IEEE TRANSACTIONS ON NUCLEAR SCIENCE Lau, F. W., Vandenbroucke, A., Reynolds, P., Ho, H., Innes, D., Levin, C. S. 2012; 59 (5): 1815-1822
View details for DOI 10.1109/TNS.2012.2209893

View details for Web of Science ID 000310142800005
Influence of temperature and bias voltage on the performance of a high resolution PET detector built with position sensitive avalanche photodiodes JOURNAL OF INSTRUMENTATION Vandenbroucke, A., McLaughlin, T. J., Levin, C. S. 2012; 7
View details for DOI 10.1088/1748-0221/7/08/P08001

View details for Web of Science ID 000308869800012
Study of PET intrinsic spatial resolution and contrast recovery improvement for PET/MRI systems PHYSICS IN MEDICINE AND BIOLOGY Peng, H., Levin, C. S. 2012; 57 (9)
Abstract

This paper studied PET intrinsic spatial resolution and contrast recovery improvement for PET/MRI dual modality systems. A Monte Carlo simulation tool was developed to study positron diffusion in tissues with and without a magnetic field for six commonly used isotopes ((18)F, (11)C, (13)N, (15)O, (68)Ga and (82)Rb). A convolution process was implemented to investigate PET intrinsic spatial resolution, taking into account three factors: positron diffusion range, collinear photon annihilation and finite detector element width. The resolution improvement was studied quantitatively as a function of magnetic field strength for three PET system configurations (whole-body, brain-dedicated and small-animal PET). When the magnetic field strength increases up to 10 T, the system spatial resolution in directions orthogonal to the field for (15)O, (68)Ga and (82)Rb is comparable to that of (18)F without the magnetic field. Beyond 10 T, no significant improvement of spatial resolution was observed. In addition, the modulation transfer function was studied to predict the intrinsic contrast recovery improvement for several existing and promising PET/MRI configurations.

View details for DOI 10.1088/0031-9155/57/9/N101

View details for Web of Science ID 000303046200001

View details for PubMedID 22481596
Promising New Photon Detection Concepts for High-Resolution Clinical and Preclinical PET JOURNAL OF NUCLEAR MEDICINE Levin, C. S. 2012; 53 (2): 167-170
Abstract

The ability of PET to visualize and quantify regions of low concentration of PET tracer representing subtle cellular and molecular signatures of disease depends on relatively complex biochemical, biologic, and physiologic factors that are challenging to control, as well as on instrumentation performance parameters that are, in principle, still possible to improve on. Thus, advances to the latter can somewhat offset barriers of the former. PET system performance parameters such as spatial resolution, contrast resolution, and photon sensitivity contribute significantly to PET's ability to visualize and quantify lower concentrations of signal in the presence of background. In this report we present some technology innovations under investigation toward improving these PET system performance parameters. We focus particularly on a promising advance known as 3-dimensional position-sensitive detectors, which are detectors capable of distinguishing and measuring the position, energy, and arrival time of individual interactions of multi-interaction photon events in 3 dimensions. If successful, these new strategies enable enhancements such as the detection of fewer diseased cells in tissue or the ability to characterize lower-abundance molecular targets within cells. Translating these advanced capabilities to the clinic might allow expansion of PET's roles in disease management, perhaps to earlier stages of disease. In preclinical research, such enhancements enable more sensitive and accurate studies of disease biology in living subjects.

View details for DOI 10.2967/jnumed.110.084343

View details for Web of Science ID 000300032800006

View details for PubMedID 22302960
The Trend of Data Path Structures for Data Acquisition Systems in Positron Emission Tomography 18th IEEE-NPSS Real Time Conference (RT) Kim, E., Hong, K. J., Yeom, J. Y., Olcott, P. D., Levin, C. S. IEEE. 2012
View details for Web of Science ID 000316572100091
Characterization of Detector Layers from a 1 mm(3) Resolution Clinical PET System IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Reynolds, P. D., Lau, F. W., Vandenbroucke, A., Innes, D., Yoruk, U., Levin, C. S. IEEE. 2012: 3804–3807
View details for Web of Science ID 000326814203210
Performance of Fast Timing Silicon Photomultipliers for Scintillation Detectors IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Yeom, J., Vinke, R., Pavlov, N., Bellis, S., O'Neill, K., Jackson, C., Levin, C. S. IEEE. 2012: 2845–2847
View details for Web of Science ID 000326814202209
Characterization of Inter-detector Effects in a 3-D Position-Sensitive Dual-CZT Detector Modules for PET IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Gu, Y., Levin, C. S. IEEE. 2012: 4088–4090
View details for Web of Science ID 000326814204038
Optimizing Timing Performance of Silicon Photomultiplier Based Scintillation Detectors IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Yeom, J., Vinke, R., Levin, C. S. IEEE. 2012: 3119–3121
View details for Web of Science ID 000326814203048
Timing Performance Comparison of P-on-N and N-on-P Silicon Photomultipliers IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Vinke, R., Yeom, J. Y., Mazzillo, M., Sanfilippo, D., Piana, A., Levin, C. S. IEEE. 2012: 2128–2130
View details for Web of Science ID 000326814202047
Improved Compressed Sensing Multiplexing for PET Detector Readout IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Chinn, G., Olcott, P. D., Levin, C. S. IEEE. 2012: 2472–2474
View details for Web of Science ID 000326814202123
PET DAQ System for Compressed Sensing Detector Modules IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Kim, E., Hong, K. J., Olcott, P. D., Levin, C. S. IEEE. 2012: 2798–2801
View details for Web of Science ID 000326814202198
FPGA-based Time-to-Digital Converter for Time-of-Flight PET Detector IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Hong, K. J., Kim, E., Yeom, J. Y., Olcott, P. D., Levin, C. S. IEEE. 2012: 2463–2465
View details for Web of Science ID 000326814202120
Design and Implementation of Scalable DAQ Software for a High-Resolution PET Camera IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Yoruk, U., Vandenbroucke, A., Reynolds, P. D., Levin, C. S. IEEE. 2012: 2537–2539
View details for Web of Science ID 000326814202139
A cost-effective modular programmable HV distribution system for photodetectors IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Lau, F. W., Yeom, J. Y., Vandenbroucke, A., Reynolds, P. D., Innes, D., Levin, C. S. IEEE. 2012: 3504–3506
View details for Web of Science ID 000326814203137
A Method to Achieve Spatial Linearity and Uniform Resolution at the Edges of Monolithic Scintillation Crystal Detectors for PET IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Vinke, R., Olcott, P. D., Yearn, J. Y., Levin, C. S. IEEE. 2012: 2270–2273
View details for Web of Science ID 000326814202075
GPU-Enabled PET Motion Compensation Using Sparse and Low-Rank Decomposition IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Cui, J., Yang, J., Graves, E., Levin, C. S. IEEE. 2012: 3367–3370
View details for Web of Science ID 000326814203104
Strategies to Achieve More Compact Pulse Width Modulation Circuitry for Silicon Photomultiplier Readout IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop Bieniosek, M. F., Olcott, P. D., Levin, C. S. IEEE. 2012: 3812–3814
View details for Web of Science ID 000326814203212
Readout Electronics and Data Acquisition of a Time of Flight Detector for Positron Emission Tomography 18th IEEE-NPSS Real Time Conference (RT) Yeom, J. Y., Vinke, R., Spanoudaki, V., Hong, K. J., Levin, C. S. IEEE. 2012
View details for Web of Science ID 000316572100054
Fully 3D list-mode time-of-flight PET image reconstruction on GPUs using CUDA MEDICAL PHYSICS Cui, J., Pratx, G., Prevrhal, S., Levin, C. S. 2011; 38 (12): 6775-6786
Abstract

List-mode processing is an efficient way of dealing with the sparse nature of positron emission tomography (PET) data sets and is the processing method of choice for time-of-flight (ToF) PET image reconstruction. However, the massive amount of computation involved in forward projection and backprojection limits the application of list-mode reconstruction in practice, and makes it challenging to incorporate accurate system modeling.The authors present a novel formulation for computing line projection operations on graphics processing units (GPUs) using the compute unified device architecture (CUDA) framework, and apply the formulation to list-mode ordered-subsets expectation maximization (OSEM) image reconstruction. Our method overcomes well-known GPU challenges such as divergence of compute threads, limited bandwidth of global memory, and limited size of shared memory, while exploiting GPU capabilities such as fast access to shared memory and efficient linear interpolation of texture memory. Execution time comparison and image quality analysis of the GPU-CUDA method and the central processing unit (CPU) method are performed on several data sets acquired on a preclinical scanner and a clinical ToF scanner.When applied to line projection operations for non-ToF list-mode PET, this new GPU-CUDA method is >200 times faster than a single-threaded reference CPU implementation. For ToF reconstruction, we exploit a ToF-specific optimization to improve the efficiency of our parallel processing method, resulting in GPU reconstruction >300 times faster than the CPU counterpart. For a typical whole-body scan with 75 × 75 × 26 image matrix, 40.7 million LORs, 33 subsets, and 3 iterations, the overall processing time is 7.7 s for GPU and 42 min for a single-threaded CPU. Image quality and accuracy are preserved for multiple imaging configurations and reconstruction parameters, with normalized root mean squared (RMS) deviation less than 1% between CPU and GPU-generated images for all cases.A list-mode ToF OSEM library was developed on the GPU-CUDA platform. Our studies show that the GPU reformulation is considerably faster than a single-threaded reference CPU method especially for ToF processing, while producing virtually identical images. This new method can be easily adapted to enable more advanced algorithms for high resolution PET reconstruction based on additional information such as depth of interaction (DoI), photon energy, and point spread functions (PSFs).

View details for DOI 10.1118/1.3661998

View details for Web of Science ID 000298250100045

View details for PubMedID 22149859
Online detector response calculations for high-resolution PET image reconstruction PHYSICS IN MEDICINE AND BIOLOGY Pratx, G., Levin, C. 2011; 56 (13): 4023-4040
Abstract

Positron emission tomography systems are best described by a linear shift-varying model. However, image reconstruction often assumes simplified shift-invariant models to the detriment of image quality and quantitative accuracy. We investigated a shift-varying model of the geometrical system response based on an analytical formulation. The model was incorporated within a list-mode, fully 3D iterative reconstruction process in which the system response coefficients are calculated online on a graphics processing unit (GPU). The implementation requires less than 512 Mb of GPU memory and can process two million events per minute (forward and backprojection). For small detector volume elements, the analytical model compared well to reference calculations. Images reconstructed with the shift-varying model achieved higher quality and quantitative accuracy than those that used a simpler shift-invariant model. For an 8 mm sphere in a warm background, the contrast recovery was 95.8% for the shift-varying model versus 85.9% for the shift-invariant model. In addition, the spatial resolution was more uniform across the field-of-view: for an array of 1.75 mm hot spheres in air, the variation in reconstructed sphere size was 0.5 mm RMS for the shift-invariant model, compared to 0.07 mm RMS for the shift-varying model.

View details for DOI 10.1088/0031-9155/56/13/018

View details for Web of Science ID 000291866800020

View details for PubMedID 21677367

View details for PubMedCentralID PMC3147176
A Maximum NEC Criterion for Compton Collimation to Accurately Identify True Coincidences in PET IEEE TRANSACTIONS ON MEDICAL IMAGING Chinn, G., Levin, C. S. 2011; 30 (7): 1341-1352
Abstract

In this work, we propose a new method to increase the accuracy of identifying true coincidence events for positron emission tomography (PET). This approach requires 3-D detectors with the ability to position each photon interaction in multi-interaction photon events. When multiple interactions occur in the detector, the incident direction of the photon can be estimated using the Compton scatter kinematics (Compton Collimation). If the difference between the estimated incident direction of the photon relative to a second, coincident photon lies within a certain angular range around colinearity, the line of response between the two photons is identified as a true coincidence and used for image reconstruction. We present an algorithm for choosing the incident photon direction window threshold that maximizes the noise equivalent counts of the PET system. For simulated data, the direction window removed 56%-67% of random coincidences while retaining > 94% of true coincidences from image reconstruction as well as accurately extracted 70% of true coincidences from multiple coincidences.

View details for DOI 10.1109/TMI.2011.2113379

View details for Web of Science ID 000292164900004

View details for PubMedID 21317079

View details for PubMedCentralID PMC3667991
Investigation of a clinical PET detector module design that employs large-area avalanche photodetectors PHYSICS IN MEDICINE AND BIOLOGY Peng, H., Olcott, P. D., Spanoudaki, V., Levin, C. S. 2011; 56 (12): 3603-3627
Abstract

We investigated the feasibility of designing an Anger-logic PET detector module using large-area high-gain avalanche photodiodes (APDs) for a brain-dedicated PET/MRI system. Using Monte Carlo simulations, we systematically optimized the detector design with regard to the scintillation crystal, optical diffuser, surface treatment, layout of large-area APDs, and signal-to-noise ratio (SNR, defined as the 511 keV photopeak position divided by the standard deviation of noise floor in an energy spectrum) of the APD devices. A detector prototype was built comprising an 8 × 8 array of 2.75 × 3.00 × 20.0 mm3 LYSO (lutetium-yttrium-oxyorthosilicate) crystals and a 22.0 × 24.0 × 9.0 mm3 optical diffuser. From the four designs of the optical diffuser tested, two designs employing a slotted diffuser are able to resolve all 64 crystals within the block with good uniformity and peak-to-valley ratio. Good agreement was found between the simulation and experimental results. For the detector employing a slotted optical diffuser, the energy resolution of the global energy spectrum after normalization is 13.4 ± 0.4%. The energy resolution of individual crystals varies between 11.3 ± 0.3% and 17.3 ± 0.4%. The time resolution varies between 4.85 ± 0.04 (center crystal), 5.17 ± 0.06 (edge crystal), and 5.18 ± 0.07 ns (corner crystal). The generalized framework proposed in this work helps to guide the design of detector modules for selected PET system configurations, including scaling the design down to a preclinical PET system, scaling up to a whole-body clinical scanner, as well as replacing APDs with other novel photodetectors that have higher gain or SNR such as silicon photomultipliers.

View details for DOI 10.1088/0031-9155/56/12/010

View details for Web of Science ID 000291095700011

View details for PubMedID 21610292
Study of a high-resolution, 3D positioning cadmium zinc telluride detector for PET PHYSICS IN MEDICINE AND BIOLOGY Gu, Y., Matteson, J. L., Skelton, R. T., Deal, A. C., Stephan, E. A., Duttweiler, F., Gasaway, T. M., Levin, C. S. 2011; 56 (6): 1563-1584
Abstract

This paper investigates the performance of 1 mm resolution cadmium zinc telluride (CZT) detectors for positron emission tomography (PET) capable of positioning the 3D coordinates of individual 511 keV photon interactions. The detectors comprise 40 mm × 40 mm × 5 mm monolithic CZT crystals that employ a novel cross-strip readout with interspersed steering electrodes to obtain high spatial and energy resolution. The study found a single anode FWHM energy resolution of 3.06 ± 0.39% at 511 keV throughout most of the detector volume. Improved resolution is expected with properly shielded front-end electronics. Measurements made using a collimated beam established the efficacy of the steering electrodes in facilitating enhanced charge collection across anodes, as well as a spatial resolution of 0.44 ± 0.07 mm in the direction orthogonal to the electrode planes. Finally, measurements based on coincidence electronic collimation yielded a point spread function with 0.78 ± 0.10 mm FWHM, demonstrating 1 mm spatial resolution capability transverse to the anodes-as expected from the 1 mm anode pitch. These findings indicate that the CZT-based detector concept has excellent performance and shows great promise for a high-resolution PET system.

View details for DOI 10.1088/0031-9155/56/6/004

View details for Web of Science ID 000287848600004

View details for PubMedID 21335649

View details for PubMedCentralID PMC3274175
Investigating the temporal resolution limits of scintillation detection from pixellated elements: comparison between experiment and simulation PHYSICS IN MEDICINE AND BIOLOGY Spanoudaki, V. C., Levin, C. S. 2011; 56 (3): 735-756
Abstract

This study investigates the physical limitations involved in the extraction of accurate timing information from pixellated scintillation detectors for positron emission tomography (PET). Accurate physical modeling of the scintillation detection process, from scintillation light generation through detection, is devised and performed for varying detector attributes, such as the crystal element length, light yield, decay time and surface treatment. The dependence of light output and time resolution on these attributes, as well as on the photon interaction depth (DoI) of the annihilation quanta within the crystal volume, is studied and compared with experimental results. A theoretical background which highlights the importance of different time blurring factors for instantaneous ('ideal') and exponential ('realistic') scintillation decay is developed and compared with simulated data. For the case of a realistic scintillator, our experimental and simulation findings suggest that dependence of detector performance on DoI is more evident for crystal elements with rough ('as cut') compared to polished surfaces (maximum observed difference of 64% (25%) and 22% (19%) in simulation (measurement) for light output and time resolution, respectively). Furthermore we observe distinct trends of the detector performance dependence on detector element length and surface treatment. For short crystals (3 × 3 × 5 mm(3)) an improvement in light output and time resolution for 'as cut' compared to polished crystals is observed (3% (7%) and 9% (9%) for simulation (measurement), respectively). The trend is reversed for longer crystals (3 × 3 × 20 mm(3)) and an improvement in light output and time uncertainty for polished compared to 'as cut' crystals is observed (36% (6%) and 40% (20%) for simulation (measurement), respectively). The results of this study are used to guide the design of PET detectors with combined time of flight (ToF) and DoI features.

View details for DOI 10.1088/0031-9155/56/3/013

View details for Web of Science ID 000286223100013

View details for PubMedID 21239845
Convex Optimization of Coincidence Time Resolution for a High-Resolution PET System IEEE TRANSACTIONS ON MEDICAL IMAGING Reynolds, P. D., Olcott, P. D., Pratx, G., Lau, F. W., Levin, C. S. 2011; 30 (2): 391-400
Abstract

We are developing a dual panel breast-dedicated positron emission tomography (PET) system using LSO scintillators coupled to position sensitive avalanche photodiodes (PSAPD). The charge output is amplified and read using NOVA RENA-3 ASICs. This paper shows that the coincidence timing resolution of the RENA-3 ASIC can be improved using certain list-mode calibrations. We treat the calibration problem as a convex optimization problem and use the RENA-3's analog-based timing system to correct the measured data for time dispersion effects from correlated noise, PSAPD signal delays and varying signal amplitudes. The direct solution to the optimization problem involves a matrix inversion that grows order (n(3)) with the number of parameters. An iterative method using single-coordinate descent to approximate the inversion grows order (n). The inversion does not need to run to convergence, since any gains at high iteration number will be low compared to noise amplification. The system calibration method is demonstrated with measured pulser data as well as with two LSO-PSAPD detectors in electronic coincidence. After applying the algorithm, the 511 keV photopeak paired coincidence time resolution from the LSO-PSAPD detectors under study improved by 57%, from the raw value of 16.3 ±0.07 ns full-width at half-maximum (FWHM) to 6.92 ±0.02 ns FWHM ( 11.52 ±0.05 ns to 4.89 ±0.02 ns for unpaired photons).

View details for Web of Science ID 000286931000019

View details for PubMedID 20876008
Fast List-Mode Reconstruction for Time-of-Flight PET Using Graphics Hardware IEEE TRANSACTIONS ON NUCLEAR SCIENCE Pratx, G., Surti, S., Levin, C. 2011; 58 (1): 105-109
View details for DOI 10.1109/TNS.2010.2081376

View details for Web of Science ID 000287086900015
Scintillation induced response in passively-quenched Si-based single photon counting avalanche diode arrays OPTICS EXPRESS Spanoudaki, V. C., Levin, C. S. 2011; 19 (2): 1665-1679
Abstract

An optical electrical model which studies the response of Si-based single photon counting arrays, specifically silicon photomultipliers (SiPMs), to scintillation light has been developed and validated with analytically derived and experimental data. The scintillator-photodetector response in terms of relative pulse height, 10%-90% rise/decay times to light stimuli of different rise times (ranging from 0.1 to 5 ns) and decay times (ranging from 1 to 50 ns), as well as for different decay times of the photodetector are compared in theory and simulation. A measured detector response is used as a reference to further validate the model and the results show a mean deviation of simulated over measured values of 1%.

View details for Web of Science ID 000286314600127

View details for PubMedID 21263706
All-optical encoding of PET detector signals IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Grant, A. M., Olcott, P. D., Levin, C. S. IEEE. 2011: 2258–2260
View details for Web of Science ID 000304755602096
Fast and Accurate 3D Compton Cone Projections on GPU Using CUDA IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Cui, J., Chinn, G., Levin, C. S. IEEE. 2011: 2572–2575
View details for Web of Science ID 000304755602167
Silicon Photomultiplier-based Detector Array for TOF PET IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Yeom, J. Y., Spanoudaki, V., Levin, C. S. IEEE. 2011: 2415–2417
View details for Web of Science ID 000304755602130
Energy and Time Characterization of Silicon Photomultiplier Detector Blocks IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Sanjani, S. S., Taghibakhsh, F., Levin, C. S. IEEE. 2011: 3045–3047
View details for Web of Science ID 000304755603062
A New Data Path Design for a PET Data Acquisition System: A Packet Based Approach IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Kim, E., Olcott, P., Levin, C. IEEE. 2011: 3871–3873
View details for Web of Science ID 000304755604023
Functionality Test of a Readout Circuit for a 1mm(3) Resolution Clinical PET System IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Zhai, J., Vandenbroucke, A., Reynolds, P. D., Levin, C. S. IEEE. 2011: 3945–3949
View details for Web of Science ID 000304755604037
Measuring 511 ke V photon interaction locations in three dimensions using 3-D position sensitive scintillation detectors IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Vandenbroucke, A., Lau, F. W., Reynolds, P. O., Levin, C. S. IEEE. 2011: 3635–3638
View details for Web of Science ID 000304755603196
Study of Readout for Groups of Position Sensitive Avalanche Photodiodes Used in a 1 mm(3) Resolution Clinical PET System IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Reynolds, P. D., Lau, F. W., Vandenbroucke, A., Levin, C. S. IEEE. 2011: 3253–3255
View details for Web of Science ID 000304755603108
Signal Conditioning Technique for Position Sensitive Photo detectors to Manipulate Pixelated Crystal Identification Capabilities IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Lau, F. W., Vandenbroucke, A., Reynolds, P., Ho, H., Innes, D., Levin, C. S. IEEE. 2011: 1647–1653
View details for Web of Science ID 000304755601179
Measurement-Based Spatially-Varying Point Spread Function for List-Mode PET Reconstruction on GPU IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Cui, J., Pratx, G., Prevrhal, S., Zhang, B., Shao, L., Levin, C. S. IEEE. 2011: 2593–2596
View details for Web of Science ID 000304755602171
Point Spread Function for PET Detectors Based on the Probability Density Function of the Line Segment IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Gonzalez, E., Cui, J., Pratx, G., Bieniosek, M., Olcott, P. D., Levin, C. S. IEEE. 2011: 4386–4389
View details for Web of Science ID 000304755604132
Methods for Increasing the Sensitivity of Simultaneous Multi-Isotope Positron Emission Tomography IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Gonzalez, E., Olcott, P. D., Bieniosek, M., Levin, C. S. IEEE. 2011: 3597–3601
View details for Web of Science ID 000304755603187
Algorithms that exploit multi-interaction photon events in sub-millimeter resolution CZT detectors for PET IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Chinn, G., Levin, C. S. IEEE. 2011: 3669–3671
View details for Web of Science ID 000304755603203
Time Resolution Performance of an Electro-Optical-Coupled PET Detector for Time-of-Flight PET/MRI IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Bieniosek, M. F., Olcott, P. D., Levin, C. S. IEEE. 2011: 2531–2533
View details for Web of Science ID 000304755602156
Compressed Sensing for the multiplexing of PET detectors IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors Olcott, P. D., Chinn, G., Levin, C. S. IEEE. 2011: 3224–3226
View details for Web of Science ID 000304755603101
Analog signal multiplexing for PSAPD-based PET detectors: simulation and experimental validation PHYSICS IN MEDICINE AND BIOLOGY Lau, F. W., Vandenbroucke, A., Reynolds, P. D., Olcott, P. D., Horowitz, M. A., Levin, C. S. 2010; 55 (23): 7149-7174
Abstract

A 1 mm(3) resolution clinical positron emission tomography (PET) system employing 4608 position-sensitive avalanche photodiodes (PSAPDs) is under development. This paper describes a detector multiplexing technique that simplifies the readout electronics and reduces the density of the circuit board design. The multiplexing scheme was validated using a simulation framework that models the PSAPDs and front-end multiplexing circuits to predict the signal-to-noise ratio and flood histogram performance. Two independent experimental setups measured the energy resolution, time resolution, crystal identification ability and count rate both with and without multiplexing. With multiplexing, there was no significant degradation in energy resolution, time resolution and count rate. There was a relative 6.9 ± 1.0% and 9.4 ± 1.0% degradation in the figure of merit that characterizes the crystal identification ability observed in the measured and simulated ceramic-mounted PSAPD module flood histograms, respectively.

View details for DOI 10.1088/0031-9155/55/23/001

View details for Web of Science ID 000284261000015

View details for PubMedID 21081831
Physical effects of mechanical design parameters on photon sensitivity and spatial resolution performance of a breast-dedicated PET system MEDICAL PHYSICS Spanoudaki, V. C., Lau, F. W., Vandenbroucke, A., Levin, C. S. 2010; 37 (11): 5838-5849
Abstract

This study aims to address design considerations of a high resolution, high sensitivity positron emission tomography scanner dedicated to breast imaging.The methodology uses a detailed Monte Carlo model of the system structures to obtain a quantitative evaluation of several performance parameters. Special focus was given to the effect of dense mechanical structures designed to provide mechanical robustness and thermal regulation to the minuscule and temperature sensitive detectors.For the energies of interest around the photopeak (450-700 keV energy window), the simulation results predict a 6.5% reduction in the single photon detection efficiency and a 12.5% reduction in the coincidence photon detection efficiency in the case that the mechanical structures are interspersed between the detectors. However for lower energies, a substantial increase in the number of detected events (approximately 14% and 7% for singles at a 100-200 keV energy window and coincidences at a lower energy threshold of 100 keV, respectively) was observed with the presence of these structures due to backscatter. The number of photon events that involve multiple interactions in various crystal elements is also affected by the presence of the structures. For photon events involving multiple interactions among various crystal elements, the coincidence photon sensitivity is reduced by as much as 20% for a point source at the center of the field of view. There is no observable effect on the intrinsic and the reconstructed spatial resolution and spatial resolution uniformity.Mechanical structures can have a considerable effect on system sensitivity, especially for systems processing multi-interaction photon events. This effect, however, does not impact the spatial resolution. Various mechanical structure designs are currently under evaluation in order to achieve optimum trade-off between temperature stability, accurate detector positioning, and minimum influence on system performance.

View details for DOI 10.1118/1.3484059

View details for Web of Science ID 000283747600030

View details for PubMedID 21158296

View details for PubMedCentralID PMC2980543
Photo-Detectors for Time of Flight Positron Emission Tomography (ToF-PET) SENSORS Spanoudaki, V. C., Levin, C. S. 2010; 10 (11): 10484-10505
Abstract

We present the most recent advances in photo-detector design employed in time of flight positron emission tomography (ToF-PET). PET is a molecular imaging modality that collects pairs of coincident (temporally correlated) annihilation photons emitted from the patient body. The annihilation photon detector typically comprises a scintillation crystal coupled to a fast photo-detector. ToF information provides better localization of the annihilation event along the line formed by each detector pair, resulting in an overall improvement in signal to noise ratio (SNR) of the reconstructed image. Apart from the demand for high luminosity and fast decay time of the scintillation crystal, proper design and selection of the photo-detector and methods for arrival time pick-off are a prerequisite for achieving excellent time resolution required for ToF-PET. We review the two types of photo-detectors used in ToF-PET: photomultiplier tubes (PMTs) and silicon photo-multipliers (SiPMs) with a special focus on SiPMs.

View details for DOI 10.3390/s101110484

View details for Web of Science ID 000284578200058

View details for PubMedID 22163482

View details for PubMedCentralID PMC3230997
Performance characterization of a new high resolution PET scintillation detector PHYSICS IN MEDICINE AND BIOLOGY Vandenbroucke, A., Foudray, A. M., Olcott, P. D., Levin, C. S. 2010; 55 (19): 5895-5911
Abstract

Performance of a new high resolution PET detection concept is presented. In this new concept, annihilation radiation enters the scintillator detectors edge-on. Each detector module comprises two 8 × 8 LYSO scintillator arrays of 0.91 × 0.91 × 1 mm(3) crystals coupled to two position-sensitive avalanche photodiodes (PSAPDs) mounted on a flex circuit. Appropriate crystal segmentation allows the recording of all three spatial coordinates of the interaction(s) simultaneously with submillimeter resolution. We report an average energy resolution of 14.6 ± 1.7% for 511 keV photons at FWHM. Coincident time resolution was determined to be 2.98 ± 0.13 ns FWHM on average. The coincidence point spread function (PSF) has an average FWHM of 0.837 ± 0.049 mm (using a 500 μm spherical source) and is uniform across the arrays. Both PSF and coincident time resolution degrade when Compton interactions are included in the data. Different blurring factors were evaluated theoretically, resulting in a calculated PSF of 0.793 mm, in good agreement with the measured value.

View details for DOI 10.1088/0031-9155/55/19/018

View details for Web of Science ID 000282061800018

View details for PubMedID 20844332
Effects of multiple-interaction photon events in a high-resolution PET system that uses 3-D positioning detectors MEDICAL PHYSICS Gu, Y., Pratx, G., Lau, F. W., Levin, C. S. 2010; 37 (10): 5494-5508
Abstract

The authors' laboratory is developing a dual-panel, breast-dedicated PET system. The detector panels are built from dual-LSO-position-sensitive avalanche photodiode (PSAPD) modules-units holding two 8 x 8 arrays of 1 mm3 LSO crystals, where each array is coupled to a PSAPD. When stacked to form an imaging volume, these modules are capable of recording the 3-D coordinates of individual interactions of a multiple-interaction photon event (MIPE). The small size of the scintillation crystal elements used increases the likelihood of photon scattering between crystal arrays. In this article, the authors investigate how MIPEs impact the system photon sensitivity, the data acquisition scheme, and the quality and quantitative accuracy of reconstructed PET images.A Monte Carlo simulated PET scan using the dual-panel system was performed on a uniformly radioactive phantom for the photon sensitivity study. To establish the impact of MIPEs on a proposed PSAPD multiplexing scheme, experimental data were collected from a dual-LSO-PSAPD module edge-irradiated with a 22Na point source, the data were compared against simulation data based on an identical setup. To assess the impact of MIPEs on the dual-panel PET images, a simulated PET of a phantom comprising a matrix of hot spherical radiation sources of varying diameters immersed in a warm background was performed. The list-mode output data were used for image reconstruction, where various methods were used for estimating the location of the first photon interaction in MIPEs for more accurate line of response positioning. The contrast recovery coefficient (CRC), contrast to noise ratio (CNR), and the full width at half maximum spatial resolution of the spheres in the reconstructed images were used as figures of merit to facilitate comparison.Compared to image reconstruction employing only events with interactions confined to one LSO array, a potential single photon sensitivity gain of > 46.9% (> 115.7% for coincidence) was noted for a uniform phantom when MIPEs with summed-energy falling within a +/- 12% window around the photopeak were also included. Both experimental and simulation data demonstrate that < 0.4% of the events whose summed-energy deposition falling within that energy window interacted with both crystal arrays within the same dual-LSO-PSAPD module. This result establishes the feasibility of a proposed multiplexed readout of analog output signals of the two PSAPDs within each module. Using MIPEs with summed-energy deposition within the 511 keV +/- 12% photopeak window and a new method for estimating the location of the first photon interaction in MIPEs, the corresponding reconstructed image exhibited a peak CNR of 7.23 for the 8 mm diameter phantom spheres versus a CNR of 6.69 from images based solely on single LSO array interaction events. The improved system photon sensitivity could be exploited to reduce the scan time by up to approximately 10%, while still maintaining image quality comparable to that achieved if MIPEs were excluded.MIPE distribution in the detectors allows the proposed photodetector multiplexing arrangement without significant information loss. Furthermore, acquiring MIPEs can enhance system photon sensitivity and improve PET image CNR and CRC. The system under development can therefore competently acquire and analyze MIPEs and produce high-resolution PET images.

View details for DOI 10.1118/1.3483262

View details for Web of Science ID 000283483700038

View details for PubMedID 21089785

View details for PubMedCentralID PMC2962664
Recent Developments in PET Instrumentation CURRENT PHARMACEUTICAL BIOTECHNOLOGY Peng, H., Levin, C. S. 2010; 11 (6): 555-571
Abstract

Positron emission tomography (PET) is used in the clinic and in vivo small animal research to study molecular processes associated with diseases such as cancer, heart disease, and neurological disorders, and to guide the discovery and development of new treatments. This paper reviews current challenges of advancing PET technology and some of newly developed PET detectors and systems. The paper focuses on four aspects of PET instrumentation: high photon detection sensitivity; improved spatial resolution; depth-of-interaction (DOI) resolution and time-of-flight (TOF). Improved system geometry, novel non-scintillator based detectors, and tapered scintillation crystal arrays are able to enhance the photon detection sensitivity of a PET system. Several challenges for achieving high resolution with standard scintillator-based PET detectors are discussed. Novel detectors with 3-D positioning capability have great potential to be deployed in PET for achieving spatial resolution better than 1 mm, such as cadmium-zinc-telluride (CZT) and position-sensitive avalanche photodiodes (PSAPDs). DOI capability enables a PET system to mitigate parallax error and achieve uniform spatial resolution across the field-of-view (FOV). Six common DOI designs, as well as advantages and limitations of each design, are discussed. The availability of fast scintillation crystals such as LaBr(3), and the silicon photomultiplier (SiPM) greatly advances TOF-PET development. Recent instrumentation and initial results of clinical trials are briefly presented. If successful, these technology advances, together with new probe molecules, will substantially enhance the molecular sensitivity of PET and thus increase its role in preclinical and clinical research as well as evaluating and managing disease in the clinic.

View details for Web of Science ID 000281435100003

View details for PubMedID 20497121
Design study of a high-resolution breast-dedicated PET system built from cadmium zinc telluride detectors PHYSICS IN MEDICINE AND BIOLOGY Peng, H., Levin, C. S. 2010; 55 (9): 2761-2788
Abstract

We studied the performance of a dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging using Monte Carlo simulation. The proposed system consists of two 4 cm thick 12 x 15 cm(2) area cadmium zinc telluride (CZT) panels with adjustable separation, which can be put in close proximity to the breast and/or axillary nodes. Unique characteristics distinguishing the proposed system from previous efforts in breast-dedicated PET instrumentation are the deployment of CZT detectors with superior spatial and energy resolution, using a cross-strip electrode readout scheme to enable 3D positioning of individual photon interaction coordinates in the CZT, which includes directly measured photon depth-of-interaction (DOI), and arranging the detector slabs edge-on with respect to incoming 511 keV photons for high photon sensitivity. The simulation results show that the proposed CZT dual-panel PET system is able to achieve superior performance in terms of photon sensitivity, noise equivalent count rate, spatial resolution and lesion visualization. The proposed system is expected to achieve approximately 32% photon sensitivity for a point source at the center and a 4 cm panel separation. For a simplified breast phantom adjacent to heart and torso compartments, the peak noise equivalent count (NEC) rate is predicted to be approximately 94.2 kcts s(-1) (breast volume: 720 cm(3) and activity concentration: 3.7 kBq cm(-3)) for a approximately 10% energy window around 511 keV and approximately 8 ns coincidence time window. The system achieves 1 mm intrinsic spatial resolution anywhere between the two panels with a 4 cm panel separation if the detectors have DOI resolution less than 2 mm. For a 3 mm DOI resolution, the system exhibits excellent sphere resolution uniformity (sigma(rms)/mean) < or = 10%) across a 4 cm width FOV. Simulation results indicate that the system exhibits superior hot sphere visualization and is expected to visualize 2 mm diameter spheres with a 5:1 activity concentration ratio within roughly 7 min imaging time. Furthermore, we observe that the degree of spatial resolution degradation along the direction orthogonal to the two panels that is typical of a limited angle tomography configuration is mitigated by having high-resolution DOI capabilities that enable more accurate positioning of oblique response lines.

View details for DOI 10.1088/0031-9155/55/9/022

View details for Web of Science ID 000276816400022

View details for PubMedID 20400807
Effects of External Shielding on the Performance of a 1 mm(3) Resolution Breast PET Camera IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Vandenbroucke, A., Innes, D., Levin, C. S. IEEE. 2010: 3644–3648
View details for Web of Science ID 000306402903180
Analytic Pulse Height Correction in Dual-Ended Readout PET Detectors IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Taghibakhsh, F., Levin, C. S., Rowlands, J. A. IEEE. 2010: 2151–2154
View details for Web of Science ID 000306402902067
Optical Network-based PET DAQ System: One Fiber Optical Connection IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Kim, E., Olcott, P., Levin, C. IEEE. 2010: 2020–2025
View details for Web of Science ID 000306402902037
Fully 3-D List-mode Positron Emission Tomography Image Reconstruction on GPU using CUDA IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Cui, J., Pratx, G., Prevrhal, S., Shao, L., Levin, C. S. IEEE. 2010: 2635–2637
View details for Web of Science ID 000306402902173
Readout Design and Validation for a 1 mm(3) Resolution Clinical PET System IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Reynolds, P. D., Lau, F. W., Vandenbroucke, A., Levin, C. S. IEEE. 2010: 3097–3099
View details for Web of Science ID 000306402903058
Improving SNR with a Maximum Likelihood Compressed Sensing Decoder for Multiplexed PET Detectors IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Chinn, G., Olcott, P. D., Levin, C. S. IEEE. 2010: 3353–3356
View details for Web of Science ID 000306402903115
Mixture Model for Fast Estimation of Positron Range IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Olcott, P. D., Gonzalez, E., Vandenbroucke, A., Levin, C. S. IEEE. 2010: 3058–3060
View details for Web of Science ID 000306402903049
Acceleration of PET Monte Carlo simulation using the graphics hardware ray-tracing engine IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors Wang, Z., Olcott, P. D., Levin, C. S. IEEE. 2010: 1848–1855
View details for Web of Science ID 000306402902001
Novel Electro-Optical Coupling Technique for Magnetic Resonance-Compatible Positron Emission Tomography Detectors MOLECULAR IMAGING Olcott, P. D., Peng, H., Levin, C. S. 2009; 8 (2): 74-86
Abstract

A new magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) detector design is being developed that uses electro-optical coupling to bring the amplitude and arrival time information of high-speed PET detector scintillation pulses out of an MRI system. The electro-optical coupling technology consists of a magnetically insensitive photodetector output signal connected to a nonmagnetic vertical cavity surface emitting laser (VCSEL) diode that is coupled to a multimode optical fiber. This scheme essentially acts as an optical wire with no influence on the MRI system. To test the feasibility of this approach, a lutetium-yttrium oxyorthosilicate crystal coupled to a single pixel of a solid-state photomultiplier array was placed in coincidence with a lutetium oxyorthosilicate crystal coupled to a fast photomultiplier tube with both the new nonmagnetic VCSEL coupling and the standard coaxial cable signal transmission scheme. No significant change was observed in 511 keV photopeak energy resolution and coincidence time resolution. This electro-optical coupling technology enables an MRI-compatible PET block detector to have a reduced electromagnetic footprint compared with the signal transmission schemes deployed in the current MRI/PET designs.

View details for DOI 10.2310/7290.2009.00012

View details for Web of Science ID 000265948200004

View details for PubMedID 19397853
Bayesian reconstruction of photon interaction sequences for high-resolution PET detectors. Physics in Medicine and Biology. Selected as Feature Article of the Month, American Institute of Physics, August Pratx, G., Levin, CS. 2009; Vol. 54 (Issue 17,): pp. 5073-5094,
1 mm(3) Resolution Breast-Dedicated PET System IEEE Nuclear Science Symposium/Medical Imaging Conference Lau, F. W., Fang, C., Reynolds, P. D., Olcott, P. D., Vandenbroucke, A., Spanoudaki, V. C., Olutade, F., Horowitz, M. A., Levin, C. S. IEEE. 2009: 5378–5381
View details for Web of Science ID 000268656002327
Front-End Electronics for a 1 mm(3) Resolution Avalanche Photodiode-Based PET System with Analog Signal Multiplexing IEEE Nuclear Science Symposium/Medical Imaging Conference Lau, F. W., Vandenbroucke, A., Reynolds, P. D., Olcott, P. D., Horowitz, M. A., Levin, C. S. IEEE. 2009: 3146–3149
View details for Web of Science ID 000268656001256
Study of a High Resolution, 3-D Positioning Cross-Strip Cadmium Zinc Telluride Detector for PET IEEE Nuclear Science Symposium/Medical Imaging Conference Gu, Y., Matteson, J. L., Skelton, R. T., Deal, A. C., Stephan, E. A., Duttweiler, F., Gasaway, T. M., Levin, C. S. IEEE. 2009: 2871–2878
View details for Web of Science ID 000268656001200
Effects of Multiple Photon Interactions in a High Resolution PET System that Uses 3-D Positioning Detectors IEEE Nuclear Science Symposium/Medical Imaging Conference Gu, Y., Pratx, G., Lau, F. W., Levin, C. S. IEEE. 2009: 3089–3094
View details for Web of Science ID 000268656001243
Effects of Thermal Regulation Structures on the Photon Sensitivity and Spatial Resolution of a 1 mm(3) Resolution Breast-Dedicated PET System IEEE Nuclear Science Symposium/Medical Imaging Conference Spanoudaki, V. C., Vandenbroucke, A., Lau, F. W., Fang, C., Levin, C. S. IEEE. 2009: 5416–5420
View details for Web of Science ID 000268656002334
Performance characterization of a new high resolution PET scintillation detector IEEE Nuclear Science Symposium/Medical Imaging Conference Vandenbroucke, A., Foudray, A. M., Lau, F. W., Olcott, P. D., Reynolds, P. D., Levin, C. S. IEEE. 2009: 2879–2883
View details for Web of Science ID 000268656001201
New Geometry for a Whole Body PET System. Submitted to IEEE Transactions on Nuclear Science, F. Habte,, G. Pratx, P.D. Olcott, C.S. Levin. 2009
High Resolution, Light Multiplexed 3D Positioning Scintillation Detector for High Resolution PET. Submitted to IEEE Transactions on Nuclear Science F. Habte,, P.D. Olcott, C.S. Levin. 2009
Online calculation of the detector response for high-resolution PET iterative image reconstruction. Submitted to IEEE Transactions on Medical Imaging G. Pratx,, C.S. Levin. 2009
Maximum NEC Incident Photon Direction Window Using Compton Kinematics for 3-D Positioning PET Detectors. Submitted to IEEE Transactions on Medical Imaging G. Chinn,, C.S. Levin. 2009
Can large-area avalanche photodiodes be used for a clinical PET/MRI block detector? IEEE Nuclear Science Symposium/Medical Imaging Conference Peng, H., Olcott, P. D., Spanoudaki, V., Levin, C. S. IEEE. 2009: 3948–3953
View details for Web of Science ID 000268656002037
Convex Optimization of Coincidence Time Resolution for High Resolution PET Systems IEEE Nuclear Science Symposium/Medical Imaging Conference Reynolds, P. D., Olcott, P. D., Pratx, G., Lau, F. W., Levin, C. S. IEEE. 2009: 3343–3348
View details for Web of Science ID 000268656001302
Pulse Width Modulation: a Novel Readout Scheme for High Energy Photon Detection IEEE Nuclear Science Symposium/Medical Imaging Conference Olcott, P. D., Levin, C. S. IEEE. 2009: 3804–3809
View details for Web of Science ID 000268656002008
Novel Electro-Optically Coupled MR-Compatible PET Detectors IEEE Nuclear Science Symposium/Medical Imaging Conference Olcott, P. D., Peng, H., Levin, C. S. IEEE. 2009: 3913–3918
View details for Web of Science ID 000268656002030
Charge Collection Studies of a High Resolution CZT-Based Detector for PET IEEE Nuclear Science Symposium/Medical Imaging Conference Matteson, J. L., Gu, Y., Skelton, R. T., Deal, A. C., Stephan, E. A., Duttweiler, F., Huszar, G. L., Gasaway, T. M., Levin, C. S. IEEE. 2009: 5310–5317
View details for Web of Science ID 000268656002315
Optimization of Coincidence Time Resolution for a High Resolution PET System. Submitted to IEEE Transactions on Medical Imaging P.D. Reynolds,, P.D. Olcott, G. Pratx, F.W.Y. Lau, C.S. Levin. 2009
Design study of a high-resolution breast-dedicated PET system built from cadmium zinc telluride detectors. Submitted to Physics in Medicine Biology H. Peng,, P.D. Olcott, C.S. Levin. 2009
Monte Carlo assessment of a dense mechanical design for a 1 mm3 resolution breast-dedicated PET system: effects on photon sensitivity, spatial resolution and multi-interaction photon events. Submitted to Medical Physics V.C. Spanoudaki,, F.W.Y. Lau, A. Vandenbroucke, C.S. Levin. 2009
Study of a High Resolution, 3-D Positioning Cross-Strip Cadmium Zinc Telluride Detector for PET. Submitted to Medical Physics Y. Gu,, J. L. Matteson, R.T. Skelton, A.C. Deal, E.A. Stephan, F. Duttweiler, T. M. Gasaway, C.S. Levin. 2009
Sampling Error in CT-based Partial Volume Correction of Lesions Imaged by PET. Submitted to Journal of Nuclear Medicine D. M. Sigg,, C.S. Levin, A. Quon. 2009
Can large-area avalanche photodiodes be used for a PET detector insert for an MRI system? Submitted to Medical Physics H. Peng,, P.D. Olcott, V. Spanoudaki, C.S. Levin. 2009
A Method to Reject Random Coincidences and Extract True from Multiple Coincidences in PET using 3-D Detectors IEEE Nuclear Science Symposium/Medical Imaging Conference Chinn, G., Levin, C. S. IEEE. 2009: 4515–4520
View details for Web of Science ID 000268656002154
Faster Maximum-Likelihood Reconstruction via Explicit Conjugation of Search Directions IEEE Nuclear Science Symposium/Medical Imaging Conference Pratx, G., Reader, A. J., Levin, C. S. IEEE. 2009: 4336–4341
View details for Web of Science ID 000268656002118
Study of Scintillation Crystal Array Parameters for an Advanced PET Scanner Dedicated to Breast Cancer Imaging IEEE Nuclear Science Symposium/Medical Imaging Conference Vandenbroucke, A., Levin, C. S. IEEE. 2009: 4180–4185
View details for Web of Science ID 000268656002086
Temperature and Bias Voltage Studies of a Large Area Position Sensitive Avalanche Photodiode IEEE Nuclear Science Symposium Conference 2009 Vandenbroucke, A., Lee, J., Spanoudaki, V., Lau, F. W., Reynolds, P. D., Levin, C. S. IEEE. 2009: 3664–3669
View details for Web of Science ID 000280505102062
Performance characterization of a new high resolution PET scintillation detector. Submitted to Physics in Medicine and Biology A. Vandenbrouke,, A.M.K. Foudray, P.D. Olcott, C.S. Levin. 2009
Fast, Accurate and Shift-Varying Line Projections for Iterative Reconstruction Using the GPU. IEEE Transactions in Medical Imaging, March G. Pratx,, P.D. Olcott, G. Chinn, C.S. Levin. 2009; Vol. 28, (No. 3,): 435-445
Multiplexing circuits for PSAPD-Based PET Detectors: Simulation and Experimental Validation. Submitted to IEEE Transactions on Nuclear Science F.W.Y. Lau,, A. Vandenbrouke, P.D. Reynolds, P.D. Olcott, M.A. Horowitz, C.S. Levin. 2009
Simulation study of PET spatial resolution and contrast recovery improvement for PET/MRI dual modality systems. Submitted to Medical Physics H. Peng, C.S Levin, B.A Chronik. 2009
Novel Electro-Optical Coupling Technique for Magnetic Resonance-Compatible Positron Emission Tomography Detectors. Molecular Imaging, MAR-APR P.D. Olcott,, H. Peng, C.S. Levin. 2009; Volume 8, (Issue 2,): 74-86,
New geometry for a whole body PET system. Submitted to IEEE Transactions on Nuclear Science F. Habte,, G. Pratx, P. Olcott, C.S Levin. 2009
New imaging technologies to enhance the molecular sensitivity of positron emission tomography PROCEEDINGS OF THE IEEE Levin, C. S. 2008; 96 (3): 439-467
View details for DOI 10.1109/JPROC.2007.913504

View details for Web of Science ID 000253299600006
Characterization of a Small Animal Time-Domain Fluorescence Tomography Imaging System., IEEE Transactions on Medical Imaging. Jan. S. Keren, O. Gheysens, C.S. Levin, S.S. Gambhir. 2008; Volume 27 (Issue 1,): Page(s):58 - 63.
New Imaging Technologies to Enhance the Molecular Sensitivity of Positron Emission Tomography. Proceedings of the IEEE, March C.S. Levin. 2008; Vol.96, (No.3,): pp. 439-67.
Simulation and Measurement of Gamma-Ray and Annihilation Photon Imaging Detectors. IEEE Transactions on Nuclear Science. F. Habte,, P.D. Olcott, A.M.K. Foudray, C.S. Levin, J. Zhang, G. Chinn. 2008: Undergoing review,
Performance characterization of a miniature, high sensitivity gamma ray camera IEEE TRANSACTIONS ON NUCLEAR SCIENCE Olcott, P. D., Habte, F., Foudray, A. M., Levin, C. S. 2007; 54 (5): 1492-1497
View details for DOI 10.1109/TNS.2007.902367

View details for Web of Science ID 000250313600006
Effects of system geometry and other physical factors on photon sensitivity of high-resolution positron emission tomography PHYSICS IN MEDICINE AND BIOLOGY Habte, F., Foudray, A. M., Olcott, P. D., Levin, C. S. 2007; 52 (13): 3753-3772
Abstract

We are studying two new detector technologies that directly measure the three-dimensional coordinates of 511 keV photon interactions for high-resolution positron emission tomography (PET) systems designed for small animal and breast imaging. These detectors are based on (1) lutetium oxyorthosilicate (LSO) scintillation crystal arrays coupled to position-sensitive avalanche photodiodes (PSAPD) and (2) cadmium zinc telluride (CZT). The detectors have excellent measured 511 keV photon energy resolutions (8% photon sensitivity for the LSO-PSAPD box configuration and >15% for CZT box geometry, using a 350-650 keV energy window setting. These simulation results compare well with analytical estimations. The trend is different for a clinical whole-body PET system that uses conventional LSO-PMT block detectors with larger crystal elements. Simulations predict roughly the same sensitivity for both box and cylindrical detector configurations. This results from the fact that a large system diameter (>80 cm) results in relatively small inter-module gaps in clinical whole-body PET. In addition, the relatively large block detectors (typically >5 x 5 cm(2) cross-sectional area) and large crystals (>4 x 4 x 20 mm(3)) enable a higher fraction of detector scatter photons to be absorbed compared to a small animal system. However, if the four detector sides (panels) of a box-shaped system geometry are configured to move with respect to each other, to better fit the transaxial FOV to the actual size of the object to be imaged, a significant increase in photon sensitivity is possible. Simulation results predict a 60-100% relative increase of photon sensitivity for the proposed small animal PET box configurations and >60% increase for a clinical whole-body system geometry. Thus, simulation results indicate that for a PET system built from rectangular-shaped detector modules, arranging them into a box-shaped system geometry may help us to significantly boost photon sensitivity for both small animal and clinical PET systems.

View details for DOI 10.1088/0031-9155/52/13/007

View details for Web of Science ID 000247048300007

View details for PubMedID 17664575
A new positioning algorithm for position-sensitive avalanche photodiodes IEEE TRANSACTIONS ON NUCLEAR SCIENCE Zhang, J., Olcott, P. D., Levin, C. S. 2007; 54 (3): 433-437
View details for DOI 10.1109/TNS.2007.894129

View details for Web of Science ID 000247391200004
Performance characterization of a novel thin position-sensitive avalanche photodiode for 1 mm resolution positron emission tomography IEEE TRANSACTIONS ON NUCLEAR SCIENCE Zhang, J., Foudray, A. M., Cott, P. D., Farrell, R., Shah, K., Levin, C. S. 2007; 54 (3): 415-421
View details for DOI 10.1109/TNS.2007.894128

View details for Web of Science ID 000247391200001
Current Trends in Preclinical PET System Design. PET clinics Levin, C. S., Zaidi, H. 2007; 2 (2): 125-160
Abstract

PET is used in laboratory small-animal research to visualize and track certain molecular processes associated with diseases such as cancer, heart disease, and neurologic disorders in living small-animal models of disease. The current and next generation of PET molecular imaging probes, assays, and imaging systems still have substantial room to improve PET's ability to detect, visualize, and quantify low concentrations of probe interacting with its target, which we refer to as the molecular sensitivity. This article focuses on the challenges of advancing PET system and some of the new imaging system technologies under investigation to enhance PET's molecular sensitivity substantially.

View details for DOI 10.1016/j.cpet.2007.12.001

View details for PubMedID 27157870
Study of the performance of a novel 1 mm resolution dual-panel PET camera design dedicated to breast cancer imaging using Monte Carlo simulation MEDICAL PHYSICS Zhang, J., Olcott, P. D., Chinn, G., Foudray, A. M., Levin, C. S. 2007; 34 (2): 689-702
Abstract

We studied the performance of a dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging using Monte Carlo simulation. The PET camera under development has two 10x 15 cm(2) plates that are constructed from arrays of I X 1 X 3 mm(3) LSO crystals coupled to novel ultra-thin (<200 Am) silicon position-sensitive avalanche photodiodes (PSAPD). In this design the photodetectors are configured "edge-on" with respect to incoming photons which encounter a minimum of 2 cm thick of LSO with directly measured photon interaction depth. Simulations predict that this camera will have 10-15% photon sensitivity, for an 8-4 cm panel separation. Detector measurements show approximately 1 mm(3) intrinsic spatial resolution, <12% energy resolution, and approximately 2 ns coincidence time resolution. By performing simulated dual-panel PET studies using a phantom comprising active breast, heart, and torso tissue, count performance was studied as a function of coincident time and energy windows. We also studied visualization of hot spheres of 2.5-4.0 mm diameter and various locations within the simulated breast tissue for 1 X 1 X 3 mm(3), 2 x 2 x 10 mm(3), 3 x 3 x 30 mm(3), and 4 X 4 X 20 mm(3) LSO crystal resolutions and different panel separations. Images were reconstructed by focal plane tomography with attenuation and normalization corrections applied. Simulation results indicate that with an activity concentration ratio of tumor:breast:heart:torso of 10:1:10:1 and 30 s of acquisition time, only the dual-plate PET camera comprising 1 X 1 X 3 mm(3) crystals could resolve 2.5 mm diameter spheres with an average peak-to-valley ratio of 1.3.

View details for DOI 10.1118/1.2409480

View details for Web of Science ID 000244424200035

View details for PubMedID 17388187
Prototype parallel readout system for position sensitive PMT based gamma ray imaging systems IEEE TRANSACTIONS ON NUCLEAR SCIENCE Habte, F., Olcott, P. D., Levin, C. S., Foudray, A. M. 2007; 54 (1): 60-65
View details for DOI 10.1109/TNS.2006.889157

View details for Web of Science ID 000244311600009
Performance Characterization of a Miniature, High Sensitivity Gamma-Ray Camera. IEEE Transactions on Nuclear Science. Part 1 OCT P.D. Olcott,, F. Habte, C.S. Levin, A.M.K. Foudray. 2007; 54(5): 1492-1497
Noise analysis of LSO-PSAPD PET detector front-end multiplexing circuits IEEE Nuclear Science Symposium/Medical Imaging Conference Lau, F. W., Olcott, P. D., Horowitz, M. A., Peng, H., Levin, C. S. IEEE. 2007: 3212–3219
View details for Web of Science ID 000257380402138
A New Positioning Algorithm for Position-Sensitive Avalanche Photodiodes. IEEE transactions on nuclear science Zhang, J., Olcott, P. D., Levin, C. S. 2007; 54 (3)
Abstract

We are using a novel position sensitive avalanche photodiode (PSAPD) for the construction of a high resolution positron emission tomography (PET) camera. Up to now most researchers working with PSAPDs have been using an Anger-like positioning algorithm involving the four corner readout signals of the PSAPD. This algorithm yields a significant non-linear spatial "pin-cushion" distortion in raw crystal positioning histograms. In this paper, we report an improved positioning algorithm, which combines two diagonal corner signals of the PSAPD followed by a 45° rotation to determine the X or Y position of the interaction. We present flood positioning histogram data generated with the old and new positioning algorithms using a 3 × 4 array of 2 × 2 × 3 mm3 and a 3 × 8 array of 1 × 1 × 3 mm3 of LSO crystals coupled to 8 × 8 mm2 PSAPDs. This new algorithm significantly reduces the pin-cushion distortion in raw flood histogram image.

View details for PubMedID 24307743

View details for PubMedCentralID PMC3846097
Effects of System Geometry and Other Physical Factors on Photon Sensitivity of High Resolution Positron Emission Tomography. Physics in Medicine and. Biology. F. Habte,, A.M.K. Foudray, P.D. Olcott, C.S. Levin. 2007; 52: 3753-3772.
A New Positioning Algorithm for Position-Sensitive Avalanche Photodiodes. IEEE Transactions on Nuclear Science. J. Zhang,, P.D. Olcott, C.S. Levin. 2007; Volume 54 (3, Part 1): Page(s):433 ? 437.
Study of the Performance of a Novel 1 mm Resolution Dual-Panel PET Camera Design Dedicated to Breast Cancer Imaging Using Monte Carlo Simulation. Medical Physics Zhang J, Olcott PD, Chinn G, Foudray AMK, Levin CS. 2007; 34(2),: 689-702
Current Trends in Pre-Clinical Positron Emission Tomography System Design. PET Clinics, C.S. Levin,, H. Zaidi. 2007; Vol. 2 (No. 2): pp 125-160
Data acquisition system design for a 1 mm(3) resolution PSAPD-based PET system IEEE Nuclear Science Symposium/Medical Imaging Conference Olcott, P. D., Lau, F. W., Levin, C. S. IEEE. 2007: 3206–3211
View details for Web of Science ID 000257380402137
Design study of a high-resolution breast-dedicated PET system built from cadmium zinc telluride detectors IEEE Nuclear Science Symposium/Medical Imaging Conference Peng, H., Olcott, P. D., Pratx, G., Foudray, A. M., Chinn, G., Levin, C. S. IEEE. 2007: 3700–3704
View details for Web of Science ID 000257380402239
Evaluation of free-running ADCs for high resolution PET data acquisition IEEE Nuclear Science Symposium/Medical Imaging Conference Peng, H., Olcott, P. D., Foudray, A. M., Levin, C. S. IEEE. 2007: 3328–3331
View details for Web of Science ID 000257380402160
Accurately positioning events in a high-resolution PET system that uses 3D CZT detectors IEEE Nuclear Science Symposium/Medical Imaging Conference Pratx, G., Levin, C. S. IEEE. 2007: 2660–2664
View details for Web of Science ID 000257380402023
PET image reconstruction with a Bayesian projector for multi-electronic collimation schemes IEEE Nuclear Science Symposium/Medical Imaging Conference Chinn, G., Levin, C. S. IEEE. 2007: 2799–2802
View details for Web of Science ID 000257380402050
Bayesian estimator for angle recovery: Event classification and reconstruction in positron emission tomography 27th International Workshop on Bayesian Inference and Maximum Entropy Methods in Science and Engineering Foudray, A. M., Levin, C. S. AMER INST PHYSICS. 2007: 362–371
View details for Web of Science ID 000251381000040
Bayesian Estimator for Angle Recovery: Event Classification and Reconstruction in Positron Emission Tomography, Journal of Bayesian Inference and Maximum Entropy Methods in Science and Engineering, American Institutes of Physics, A.M.K. Foudray, and C.S. Levin. 2007; Volume 954: pp. 362-371,
Prototype Parallel Readout System for Position Sensitive PMT based Gamma-Ray Imaging Systems. IEEE Transactions on Nuclear Science. F. Habte,, P.D. Olcott, C. S. Levin, A.M. Foudray. 2007; 54-1(1),: 60-65
Performance Characterization of a Novel Thin Position-Sensitive Avalanche Photodiode for High Resolution Positron Emission Tomography. IEEE Transactions on Nuclear Science. Part 1 June J. Zhang,, A.M.K Foudray, P.D. Olcott, C.S. Levin. 2007; Volume 54 (3): Page(s):415 - 421
Positioning annihilation photon interactions in a thin LSO crystal sheet with a position-sensitive avalanche photodiode IEEE TRANSACTIONS ON NUCLEAR SCIENCE Foudray, A. M., Habte, F., Levin, C. S., Olcott, P. D. 2006; 53 (5): 2549-2556
View details for DOI 10.1109/TNS.2006.877178

View details for Web of Science ID 000241367100012
Fully 3-D List-Mode OSEM Accelerated by Graphics Processing Units 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium Pratx, G., Chinn, G., Habte, F., Olcott, P., Levin, C. IEEE. 2006: 2196–2202
View details for Web of Science ID 000288875602054
GRAY: High Energy Photon Ray Tracer for PET Applications 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium Olcott, P. D., Buss, S. R., Levin, C. S., Pratx, G., Sramek, C. K. IEEE. 2006: 2011–2015
View details for Web of Science ID 000288875602012
Evaluation of a Dual-Head PET Camera Design Dedicated to Breast Cancer Imaging. Physica Medica. J. Zhang,, G. Chinn, A.M.K. Foudray, F. Habte, P.D. Olcott, C.S. Levin. 2006; Vol. XXI (Suppl.1): pp. 94-98
Image Processing Algorithms to Facilitate and Enhance Sentinel Node Detection using a Hand-Held Gamma-Ray Camera in Surgical Breast Cancer Staging. Physica Medica. P.D. Olcott,, C.S. Levin. 2006; Vol. XXI (Suppl. 1): pp.99-101
Characterization of Two Thin Postion-Sensitive Avalanche Photodiodes on a Single Flex Circuit for Use in 3-D Positioning PET Detectors 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium Foudray, A. M., Farrell, R., Olcott, P. D., Shah, K. S., Levin, C. S. IEEE. 2006: 2469–2472
View details for Web of Science ID 000288875602115
A high speed fully digital data acquisition system for Positron Emission Tomography 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium Olcott, P. D., Fallu-Labruyere, A., Habte, F., Levin, C. S., Warburton, W. K. IEEE. 2006: 1909–1911
View details for Web of Science ID 000288875601201
Incident Photon Direction Calculation Using Bayesian Estimation for High Energy Photon Detector Systems with 3D Positioning Capability 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium Foudray, A. M., Chinn, G., Levin, C. S. IEEE. 2006: 2008–2010
View details for Web of Science ID 000288875602011
Impact of High Energy Resolution Detectors on the Performance of a PET System Dedicated to Breast Cancer Imaging. . Physica Medica. Selected Top 10 Most Cited Papers in Physica Medica (European Journal of Medical Physics). C.S. Levin,, F. Habte, A.M.K. Foudray, J. Chang, G. Chinn. 2006; Vol. XXI (Suppl. 1): pp. 28-34
A Method to Include Single Photon Events in Image Reconstruction for a 1 mm Resolution PET System Built with Advanced 3-D Positioning Detectors 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium Chinn, G., Foudray, A. M., Levin, C. S. IEEE. 2006: 1740–1745
View details for Web of Science ID 000288875601167
Accurately Positioning and Incorporating Tissue-Scattered Photons into PET Image Reconstruction 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium Chinn, G., Foudray, A. M., Levin, C. S. IEEE. 2006: 1746–1751
View details for Web of Science ID 000288875601168
Positioning Annihilation Photon Interactions in a Thin LSO Crystal Sheet with a Position-Sensitive Avalanche Photodiodes. IEEE Transactions on Nuclear Science. A.M.K. Foudray,, F. Habte, C.S. Levin, P.D. Olcott. 2006; 53-5(1), (Part 1 Oct): 2549-2556,
Evaluation of a dual-panel PET camera design to breast cancer imaging Workshop on Nuclear Radiology of Breast Cancer Zhang, J., Chinn, G., Foudray, A. M., Habte, F., Olcott, P., Levin, C. S. IST EDITORIALI POLGRAFICI INT. 2006: 94–98
Abstract

We are developing a novel, portable dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging. With a sensitive area of approximately 150 cm(2), this camera is based on arrays of lutetium oxyorthosilicate (LSO) crystals (1x1x3 mm(3)) coupled to 11x11-mm(2) position-sensitive avalanche photodiodes (PSAPD). GATE open source software was used to perform Monte Carlo simulations to optimize the parameters for the camera design. The noise equivalent counting (NEC) rate, together with the true, scatter, and random counting rates were simulated at different time and energy windows. Focal plane tomography (FPT) was used for visualizing the tumors at different depths between the two detector panels. Attenuation and uniformity corrections were applied to images.

View details for Web of Science ID 000245817500026

View details for PubMedID 17646005
2004 Workshop on the Nuclear Radiology of Breast Cancer - Rome (Italy) October 22-23, 2004 - Preface PHYSICA MEDICA Levin, C. S., Tornai, M. P., Pani, R., Garibaldi, F., Mankoff, D. A. 2006; 21: 1-1
View details for Web of Science ID 000245817500001
Impact of high energy resolution detectors on the performance of a PET system dedicated to breast cancer imaging Workshop on Nuclear Radiology of Breast Cancer Levin, C. S., Foudray, A. M., Habte, F. IST EDITORIALI POLGRAFICI INT. 2006: 28–34
Abstract

We are developing a high resolution, high sensitivity PET camera dedicated to breast cancer imaging. We are studying two novel detector technologies for this imaging system: a scintillation detector comprising layers of small lutetium oxyorthosilicate (LSO) crystals coupled to new position sensitive avalanche photodiodes (PSAPDs), and a pure semiconductor detector comprising cadmium zinc telluride (CZT) crystal slabs with thin anode and cathode strips deposited in orthogonal directions on either side of each slab. Both detectors achieve 1 mm spatial resolution with 3-5 mm directly measured photon interaction depth resolution, which promotes uniform reconstructed spatial resolution throughout a compact, breast-size field of view. Both detector types also achieve outstanding energy resolution (<3% and <12%, respectively for LSO-PSAPD and CZT at 511 keV). This paper studies the effects that this excellent energy resolution has on the expected system performance. Results indicate the importance that high energy resolution and narrow energy window settings have in reducing background random as well as scatter coincidences without compromising statistical quality of the dedicated breast PET data. Simulations predict that using either detector type the excellent performance and novel arrangement of these detectors proposed for the system facilitate approximately 20% instrument sensitivity at the system center and a peak noise-equivalent count rate of >4 kcps for 200 microCi in a simulated breast phantom.

View details for Web of Science ID 000245817500011

View details for PubMedID 17645990
Count Rate Studies of a Box-Shaped PET Breast Imaging System Comprised of Position Sensitive Avalanche Photodiodes Utilizing Monte Carlo Simulation. Physica Medica. Angela M. K. Foudray,, F. Habte, G. Chinn, J. Zhang, Craig S. Levin. 2006; Vol. XXI (Suppl. 1): pp. 64-67
2004 Workshop on the Nuclear Radiology of Breast Cancer - Rome (Italy) October 22-23, 2004 ? Preface, Physica Medica, Levin, C., Tornai, MP; Pani, R, Garibaldi, F;, Mankoff, DM. 2006; Volume: 21 (Suppl. 1): Pages: 1-1
Image processing algorithms to facilitate and enhance sentinel node detection using a hand-held gamma ray camera in surgical breast cancer staging Workshop on Nuclear Radiology of Breast Cancer Cott, P. D., Levin, C. S. IST EDITORIALI POLGRAFICI INT. 2006: 99–101
Abstract

We have developed a miniature scintillation camera to be used in surgical cancer staging. The availability of such a compact hand-held gamma camera may in certain cases improve localization of the sentinel lymph node and reduce the duration of a surgical breast cancer staging procedure. We have investigated image processing algorithms applied to planar images that may improve node detection capabilities for breast cancer staging. We have also studied contrast enhancement methods that may be able to identify nodes that would otherwise be missed. Exposure duration for a given camera position can be adaptively shortened or increased by using an optical flow algorithm to estimate camera motion with respect to the current frame. By determining if the camera is in motion or not, the exposure time may be increased to allow more image counts to accumulate at a given camera position. Adaptive exposure time may improve the ease of use of the hand-held camera, and allow regions of interest to be imaged more effectively. We feel that these image processing techniques can improve the utility of a hand-held gamma ray imager for sentinel lymph node detection during breast cancer staging.

View details for Web of Science ID 000245817500027

View details for PubMedID 17646006
Scintillation crystal design features for a miniature gamma ray camera IEEE TRANSACTIONS ON NUCLEAR SCIENCE Dhanasopon, A. P., Levin, C. S., Foudray, A. M., Olcott, P. D., Habte, F. 2005; 52 (5): 1439-1446
View details for DOI 10.1109/TNS.2005.858178

View details for Web of Science ID 000233780800036
Compact readout electronics for position sensitive photomultiplier tubes IEEE TRANSACTIONS ON NUCLEAR SCIENCE Olcott, P. D., Talcott, J. A., Levin, C. S., Habte, F., Foudray, A. M. 2005; 52 (1): 21-27
View details for DOI 10.1109/TNS.2004.843134

View details for Web of Science ID 000228168700004
Scintillation Crystal Design Features for a Miniature Gamma-Ray Camera. IEEE Transactions on Nuclear Science, A.P. Dhanasopon,, C.S. Levin, A. M. K. Foudray, P. D. Olcott, F. Habte. 2005; 52-5(1),: 1439-1446,
Monte Carlo simulation study of a dual-plate PET camera dedicated to breast cancer Imaging Nuclear Science Symposium/Medical Imaging Conference Zhang, J., Olcott, P. D., Foudray, A. M., Chinn, G., Levin, C. S. IEEE. 2005: 1667–1671
View details for Web of Science ID 000241851902102
Finite element model based spatial linearity correction for scintillation detectors that use position sensitive avalanche photodiodes Nuclear Science Symposium/Medical Imaging Conference Olcott, P. D., Zhang, J., Levin, C. S., Habte, F., Foudray, A. M. IEEE. 2005: 2459–2462
View details for Web of Science ID 000241851904005
Performance characterization of a novel thin position-sensitive avalanche photodiode-based detector for high resolution PET Nuclear Science Symposium/Medical Imaging Conference Zhang, J., Foudray, A. M., Olcott, P. D., Levin, C. S. IEEE. 2005: 2478–2482
View details for Web of Science ID 000241851904009
Charge multiplexing readout for position sensitive avalanche photodiodes Nuclear Science Symposium/Medical Imaging Conference Olcott, P. D., Habte, F., Zhang, J., Levin, C. S. IEEE. 2005: 2935–2937
View details for Web of Science ID 000241851904112
Compact Readout Electronics for Position Sensitive Photomultiplier Tubes. IEEE Transactions on Nuclear Science, P.D. Olcott,, .A. Talcott, C.S. Levin, F. Habte, A.M.K. Foudray. 2005; 52-1(1),: 21-27,
Investigation of scintillation light multiplexing for PET detectors based on position sensitive avalanche photodiodes Nuclear Science Symposium/Medical Imaging Conference Habte, F., Olcott, P. D., Levin, C. S., Foudray, A. M. IEEE. 2005: 2027–2030
View details for Web of Science ID 000241851903044
Comparing geometries for a PET system with 3-D photon positioning capability Nuclear Science Symposium/Medical Imaging Conference Chinn, G., Foudray, A. M., Levin, C. S. IEEE. 2005: 1709–1712
View details for Web of Science ID 000241851902111
Component based normalization for PET systems with depth of interaction measurement capability Nuclear Science Symposium/Medical Imaging Conference Foudray, A. M., Chinn, G., Levin, C. S. IEEE. 2005: 2108–2111
View details for Web of Science ID 000241851903063
Primer on Molecular Imaging Technology. European Journal of Nuclear Medicine and Molecular Imaging, C.S. Levin. 2005; , 32-2,: S325-45,
Methods to extract more light from minute scintillation crystals used in an ultra-high resolution Positron Emission Tomography detector 2nd International Conference on Imaging Technologies in Biomedical Sciences Levin, C. S., Habte, F., Foudray, A. M. ELSEVIER SCIENCE BV. 2004: 35–40
View details for DOI 10.1016/j.nima.2004.03.013

View details for Web of Science ID 000222712200008
Study of low noise multichannel readout electronics for high sensitivity PET systems based on avalanche photodiode arrays IEEE TRANSACTIONS ON NUCLEAR SCIENCE Habte, F., Levin, C. S. 2004; 51 (3): 764-769
View details for DOI 10.1109/TNS.2004.829599

View details for Web of Science ID 000222644100025
Investigation of position sensitive avalanche photodiodes for a new high-resolution PET detector design IEEE TRANSACTIONS ON NUCLEAR SCIENCE Levin, C. S., Foudray, A. M., Olcott, P. D., Habte, F. 2004; 51 (3): 805-810
View details for DOI 10.1109/TNS.2004.830112

View details for Web of Science ID 000222644100032
Methods to Extract More Light from Minute Scintillation Crystals Used in an Ultra-High Resolution Positron Emission Tomography Detector. Nuclear Instruments and Methods in Physics Research A, C.S. Levin,, F. Habte, A.M. Foudray. 2004; 527(1-2):: 35-40.
Investigation of Position Sensitive Avalanche Photodiodes for a New High Resolution PET Detector Design. IEEE Transactions on Nuclear Science, C.S. Levin,, A.M.K. Foudray, P.D. Olcott, F. Habte. 2004; 51-3(2),: 805-810,
Positioning annihilation photon interactions in a thin LSO crystal sheet with a position-sensitive avalanche photodiode Nuclear Science Symposium/Medical Imaging Conference Foudray, A. M., Habte, F., Levin, C. S., Olcott, P. D. IEEE. 2004: 2985–2989
View details for Web of Science ID 000232002104070
Characterization of performance of a miniature, high sensitivity gamma ray camera Nuclear Science Symposium/Medical Imaging Conference Olcott, P. D., Habte, F., Levin, C. S., Foudray, A. M. IEEE. 2004: 3997–4000
View details for Web of Science ID 000232002105147
Simulation and measurement of gamma ray and annihilation photon imaging detectors Nuclear Science Symposium/Medical Imaging Conference Habte, F., Olcott, P. D., Foudray, A. M., Levin, C. S., Zhang, J., Chinn, G. IEEE. 2004: 4019–4022
View details for Web of Science ID 000232002105152
Scintillation crystal design features for a miniature gamma ray camera IEEE Nuclear Science Symposium/Medical Imaging Conference Dhanasopon, A. P., Levin, C. S., Foudray, A. M., Olcott, P. D., Talcott, J. A., Habte, F. IEEE. 2004: 1967–1971
View details for Web of Science ID 000223398000437
Investigation of position sensitive avalanche photodiodes for a new high resolution PET detector design IEEE Nuclear Science Symposium/Medical Imaging Conference Levin, C. S., Foudray, A. M., Olcott, P. D., Habte, F. IEEE. 2004: 2262–2266
View details for Web of Science ID 000223398000502
Prototype parallel readout system for position sensitive PMT based gamma ray imaging systems IEEE Nuclear Science Symposium/Medical Imaging Conference Habte, F., Olcott, P. D., Levin, C. S., Foudray, A. M., Talcott, J. A. IEEE. 2004: 1891–1894
View details for Web of Science ID 000223398000420
Compact readout electronics for position sensitive photomultiplier tubes IEEE Nuclear Science Symposium/Medical Imaging Conference Olcott, P. D., Talcott, J. A., Levin, C. S., Habte, F., Foudray, A. M. IEEE. 2004: 1962–1966
View details for Web of Science ID 000223398000436
Study of Low Noise Multi-Channel Readout Electronics for High Sensitivity PET Systems Based on Avalanche Photodiode Arrays. IEEE Transactions on Nuclear Science, F. Habte, and C.S. Levin. 2004; 51-3(2),: 764-9,
Detector design issues for compact nuclear emission cameras dedicated to breast imaging 1st Topical Symposium on Functional Breast Imaging with Advanced Detectors Levin, C. S. ELSEVIER SCIENCE BV. 2003: 60–74
View details for Web of Science ID 000180900800011
Detector Design Issues for Compact Nuclear Emission Cameras Dedicated to Functional Breast Imaging. Nuclear Instruments and Methods in Physics Research A, C.S. Levin. 2003; 497-1,: 60-74,
Investigation of low noise, low cost readout electronics for high sensitivity PET systems based on avalanche photodiode arrays IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC) Habte, F., Levin, C. S. IEEE. 2003: 661–665
View details for Web of Science ID 000185702500143
Initial studies of a new detector design for ultra-high resolution Positron Emission Tomography IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC) Levin, C. S., Habte, F. IEEE. 2003: 1751–1755
View details for Web of Science ID 000185702500385
Design of a high-resolution and high-sensitivity scintillation crystal array for PET with nearly complete light collection IEEE TRANSACTIONS ON NUCLEAR SCIENCE Levin, C. S. 2002; 49 (5): 2236-2243
View details for DOI 10.1109/TNS.2002.803870

View details for Web of Science ID 000179177300032
Evaluation of breast tumor detectability with two dedicated, compact scintillation cameras IEEE TRANSACTIONS ON NUCLEAR SCIENCE McElroy, D. P., Hoffman, E. J., Macdonald, L., Patt, B. E., Iwanczyk, J. S., Yamaguchi, Y., Levin, C. S. 2002; 49 (3): 794-802
View details for Web of Science ID 000178670800028
Performance analysis of an improved 3-D PET Monte Carlo simulation and scatter correction IEEE TRANSACTIONS ON NUCLEAR SCIENCE Holdsworth, C. H., Levin, C. S., Janecek, M., Dahlbom, M., Hoffman, E. J. 2002; 49 (1): 83-89
View details for Web of Science ID 000175427300015
Centered Versus Non-Centered Source For Intracoronary Artery Radiation Therapy: A Model Based on the Scripps Trial. American Heart Journal, Arbab-Zadeh, RJ Russo, V Bhargava, C.S. Levin, SK Jani, J Lucisano, PS Teirstein. 2002; 143-2: 342-8
Expanding the versatility of a more accurate accelerated Monte Carlo simulation for 3D PET: Data correction of PET emission scans using I-124 IEEE Nuclear Science Symposium Holdsworth, C. H., Dahlbom, M., Liu, A., Williams, L., Levin, C. S., Janecek, M., Hoffman, E. J. IEEE. 2002: 2105–2109
View details for Web of Science ID 000178495800461
Design of a high resolution and high sensitivity scintillation crystal array with nearly perfect light collection IEEE Nuclear Science Symposium Levin, C. S. IEEE. 2002: 48–52
View details for Web of Science ID 000178495800011
Design of a High-Resolution and High-Sensitivity Scintillation Crystal Array for PET with Nearly Complete Light Collection. IEEE Transactions on Nuclear Science, C.S. Levin. 2002; 49-5(1),: 2236-43
Evaluation of Breast Tumor Detectability with Two Dedicated, Compact Scintillation Cameras. IEEE Transactions on Nuclear Science, D.P. McElroy,, E.J. Hoffman, L. MacDonald, B.E. Patt, J.S. Iwanczyk, Y. Yamaguchi, C.S. Levin. 2002; 49-3(1),: 794-802,
Performance Analysis of an Improved 3-D PET Monte Carlo Simulation and Scatter Correction. IEEE Transactions on Nuclear Science, C.H. Holdsworth,, C.S. Levin, M. Janecek, M. Dahlbom, E.J. Hoffman. 2002; 49-1(1),: 83-89,
Investigation of microcolumnar scintillators on an optical fiber coupled compact imaging system Medical Imaging Conference (MIC) Tornai, M. P., Archer, C. N., Weisenberger, A. G., Wojcik, R., Popov, V., MAJEWSKI, S., Keppel, C. E., Levin, C. S., Tipnis, S. V., Nagarkar, V. V. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2001: 637–44
View details for Web of Science ID 000170576300005
Investigation of accelerated Monte Carlo techniques for PET simulation and 3D PET scatter correction IEEE TRANSACTIONS ON NUCLEAR SCIENCE Holdsworth, C. H., Levin, C. S., Farquhar, T. H., Dahlbom, M., Hoffman, E. J. 2001; 48 (1): 74-81
View details for Web of Science ID 000167393800011
Investigation of Microcolumnar Scintillators on an Optical Fiber Coupled Compact Imaging System. IEEE Transactions on Nuclear Science, MP Tornai, C Archer, AG Wiesenberger, R. Wojcik, V Popov, CE Keppel, CS Levin, S Majewski, SV Tipnis, VV Nagarkar. 2001; 48-3(2),: 637-44,
Investigation of Accelerated Monte Carlo Techniques for PET Simulation and 3-D PET Scatter Correction. IEEE Transactions on Nuclear Science, C. Holdsworth, C.S. Levin, M. Dahlbom, T. Farquhar, E.J. Hoffman. 2001; 48-1(1),: 74-81
Corrigendum: Calculation of Positron Range and its Effect on Positron Emission Tomography System Spatial Resolution. Physics in Medicine and Biology C.S. Levin, and E. J. Hoffman. 2000; 45-2: 559
Calculation of Positron Range and its Effect on Positron Emission Tomography System Spatial Resolution. Physics in Medicine and Biology C.S. Levin, and E.J. Hoffman. 1999; 44,: 781-799,
Investigation of accelerated monte carlo techniques for PET simulation and 3-D PET scatter correction 1999 IEEE Nuclear Science Symposium and Medical Imaging Conference Holdsworth, C. H., Levin, C. S., Farquhar, T. H., Dahlbom, M., Hoffman, E. J. IEEE. 1999: 1500–1504
View details for Web of Science ID 000089372200311
A miniature phoswich detector for gamma-ray localization and beta imaging 1997 Medical Imaging Conference Tornai, M. P., Levin, C. S., MacDonald, L. R., Holdsworth, C. H., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1998: 1166–73
View details for Web of Science ID 000074190800019
A dual detector beta-ray imaging probe with gamma-ray background suppression for use in intra-operative detection of radiolabeled tumors 7th Pisa Meeting on Advanced Detectors Hoffman, E. J., Tornai, M. P., Levin, C. S., MacDonald, L. R., Holdsworth, C. H. ELSEVIER SCIENCE BV. 1998: 511–16
View details for Web of Science ID 000074975100122
A Miniature Phoswich Detector for Gamma-Ray Localization and Beta Imaging. IEEE Transactions on Nuclear Science, M.P. Tornai,, C.S. Levin, L.R. MacDonald, C.H. Holdsworth, E.J. Hoffman. 1998; 45-3(2),: 1166-73,
A miniature phoswich detector for gamma-ray localization and beta imaging 1997 IEEE Nuclear Science Symposium and Medical Imaging Conference Tornai, M. P., Levin, C. S., MacDonald, L. R., Holdsworth, C. H., Hoffman, E. J. IEEE. 1998: 1028–1032
View details for Web of Science ID 000074401900224
A Dual Detector Beta-Ray Imaging Probe with Gamma-Ray Background Suppression for Use in Intra-Operative Detection of Radiolabeled Tumors. Nuclear Instruments and Methods in Physics Research A E.J. Hoffman,, M.P. Tornai, C.S. Levin, L.R. MacDonald, C.H. Holdsworth. 1998; 409: 511-16,
Design and performance of gamma and beta intra-operative imaging probes V International Conference on Application of Physics in Medicine and Biology (Trieste Medical Physics 96) / IX Congresso AIFB / EFOMP Medical Physics 96 / EUTECH 96 Hoffman, E. J., Tornai, M. P., Levin, C. S., MacDonald, L. R., Siegel, S. ELSEVIER SCI LTD. 1997: 243–246
View details for Web of Science ID 000074057200067
PSPMT and photodiode designs of a small scintillation camera for imaging malignant breast tumors 1996 Medical Imaging Conference (MIC) / Nuclear Science Symposium (NSS) Levin, C. S., Hoffman, E. J., Tornai, M. P., MacDonald, L. R. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1997: 1513–20
View details for Web of Science ID A1997XP91900008
Gamma and beta intra-operative imaging probes 4th International Conference on Position-Sensitive Detectors Hoffman, E. J., Tornai, M. P., Levin, C. S., MacDonald, L. R., Siegel, S. ELSEVIER SCIENCE BV. 1997: 324–29
View details for Web of Science ID A1997XU98100065
Investigation of crystal geometries for fiber coupled gamma imaging intra-operative probes 1996 Medical Imaging Conference (MIC) / Nuclear Science Symposium (NSS) Tornai, M. P., Levin, C. S., MacDonald, L. R., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1997: 1254–61
View details for Web of Science ID A1997XF30000027
Investigation of a new readout scheme for high resolution scintillation crystal arrays using photodiodes 1996 Medical Imaging Conference (MIC) / Nuclear Science Symposium (NSS) Levin, C. S., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1997: 1208–13
View details for Web of Science ID A1997XF30000019
Discrete scintillator coupled mercuric iodide photodetector arrays for breast imaging 1996 Medical Imaging Conference (MIC) / Nuclear Science Symposium (NSS) Tornai, M. P., Patt, B. E., Iwanczyk, J. S., Levin, C. S., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1997: 1127–33
View details for Web of Science ID A1997XF30000006
Development of an intraoperative gamma camera based on a 256-pixel mercuric iodide detector array 1996 Medical Imaging Conference (MIC) / Nuclear Science Symposium (NSS) Patt, B. E., Tornai, M. P., Iwanczyk, J. S., Levin, C. S., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1997: 1242–48
View details for Web of Science ID A1997XF30000025
Annihilation gamma ray background characterization and rejection for a small beta camera used for tumor localization during surgery 1996 Medical Imaging Conference (MIC) / Nuclear Science Symposium (NSS) Levin, C. S., Tornai, M. P., MacDonald, L. R., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1997: 1120–26
View details for Web of Science ID A1997XF30000005
Compton scatter and X-ray crosstalk and the use of very thin intercrystal septa in high-resolution PET detectors IEEE TRANSACTIONS ON NUCLEAR SCIENCE Levin, C. S., Tornai, M. P., Cherry, S. R., MacDonald, L. R., Hoffman, E. J. 1997; 44 (2): 218-224
View details for Web of Science ID A1997WU14300016
Gamma and Beta Intra-Operative Imaging Probes. Nuclear Instruments and Methods in Physics Research A, E.J. Hoffman, M.P. Tornai, C.S. Levin, L.R. MacDonald, S. Siegel. 1997; 392: 324-29
A new photodiode readout scheme for high resolution scintillation crystal arrays 1996 IEEE Nuclear Science Symposium and Medical Imaging Conference Levin, C. S., Hoffman, E. J. IEEE. 1997: 1223–1227
View details for Web of Science ID A1997BH59W00265
PSPMT and PIN diode designs of a small scintillation camera for imaging malignant breast tumors 1996 IEEE Nuclear Science Symposium and Medical Imaging Conference Levin, C. S., Hoffman, E. J., Tornai, M. P., MacDonald, L. R. IEEE. 1997: 1196–1200
View details for Web of Science ID A1997BH59W00259
Investigation of crystal geometries for fiber coupled gamma imaging intra-operative probes 1996 IEEE Nuclear Science Symposium and Medical Imaging Conference Tornai, M. P., Levin, C. S., MacDonald, L. R., Hoffman, E. J. IEEE. 1997: 1135–1139
View details for Web of Science ID A1997BH59W00246
Discrete scintillator coupled mercuric iodide photodetector arrays for breast imaging 1996 IEEE Nuclear Science Symposium and Medical Imaging Conference Tornai, M. P., Patt, B. E., Iwanczyk, J. S., Levin, C. S., Hoffman, E. J. IEEE. 1997: 1034–1038
View details for Web of Science ID A1997BH59W00227
Annihilation gamma ray background characterization and rejection for a positron camera 1996 IEEE Nuclear Science Symposium and Medical Imaging Conference Levin, C. S., Tornai, M. P., MacDonald, L. R., Hoffman, E. J. IEEE. 1997: 1044–1048
View details for Web of Science ID A1997BH59W00229
Development of an Intraoperative Gamma Camera Based on a 256-Pixel Mercuric Iodide Detector Array. IEEE Transactions on Nuclear Science, B.E. Patt,, M.P. Tornai, J.S. Iwanczyk, C.S. Levin, E.J. Hoffman. 1997; 44-3(2),: 1242-48,
Investigation of a New Readout Scheme for High Resolution Scintillation Crystal Arrays Using Photodiodes. IEEE Transactions on Nuclear Science C.S. Levin, and E.J. Hoffman. 1997; 44-3(2),: 1208-13
Compton Scatter and X-Ray Crosstalk and the Use of Very Thin Intercrystal Septa in High Resolution PET Detectors. IEEE Transactions on Nuclear Science C.S. Levin, M.P. Tornai, S.R. Cherry, L.R. MacDonald, E.J. Hoffman. 1997; 44-2: 18-24
Investigation of Crystal Geometries for Fiber Coupled Gamma Imaging Intra-Operative Probes. IEEE Transactions on Nuclear Science, M.P. Tornai, C.S. Levin, L.R. MacDonald, E.J. Hoffman, J. Park. 1997; 44-3(2),: 1254-61
Annihilation Gamma-Ray Background Characterization and Rejection for a Small Beta Camera Used for Tumor Localization During Surgery. IEEE Transactions on Nuclear Science C.S. Levin, M.P. Tornai, L.R. MacDonald, E.J. Hoffman. 1997; 44-4: 1120-26,
Discrete Scintillator Coupled Mercuric Iodide Photodetector Arrays for Breast Imaging. IEEE Transactions on Nuclear Science, M.P. Tornai, B.E. Patt, J.S. Iwanczyk, C.S. Levin, E.J. Hoffman. 1997; 44-3(2),: 1127-33,
PSPMT and Photodiode Designs of a Small Scintillation Camera for Imaging Malignant Breast Tumors. . IEEE Transactions on Nuclear Science, C.S. Levin, E.J. Hoffman, M.P. Tornai, L.R. MacDonald. 1997; 44-4(1),: 1513-20,
Design and Performance of Gamma and Beta Intra-Operative Imaging Probes. Physica Medica E.J. Hoffman, M.P. Tornai, C.S. Levin, L.R. MacDonald, S. Siegel. 1997; Vol. XIII (Suppl. 1): S243-247
Characterization of fluor concentration and geometry in organic scintillators for in situ beta imaging IEEE TRANSACTIONS ON NUCLEAR SCIENCE Tornai, M. P., Hoffman, E. J., MacDonald, L. R., Levin, C. S. 1996; 43 (6): 3342-3347
View details for Web of Science ID A1996WC90500019
Mercuric iodide photodetector arrays for gamma-ray imaging 9th International Workshop on Room Temperature Semiconductor X-Ray and Gamma-Ray Detectors, Associated Electronics and Applications Patt, B. E., Iwanczyk, J. S., Wang, Y. J., Tornai, M. P., Levin, C. S., Hoffman, E. J. ELSEVIER SCIENCE BV. 1996: 295–300
View details for Web of Science ID A1996VW52700066
Design considerations and initial performance of a 1.2 cm(2) beta imaging intra-operative probe 1995 Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC 95) Tornai, M. P., MacDonald, L. R., Levin, C. S., Siegel, S., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1996: 2326–35
View details for Web of Science ID A1996VD77700020
Optimizing light collection from thin scintillators used in a beta-ray camera for surgical use 1995 Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC 95) Levin, C. S., MacDonald, L. R., Tornai, M. P., Hoffman, E. J., Park, J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1996: 2053–60
View details for Web of Science ID A1996UT04400179
Mercuric Iodide Photodetector Arrays for Gamma-Ray Imaging. Nuclear Instruments and Methods in Physics Research A, B.E. Patt, J.S. Iwanczyk, Y.J. Wang, M.P. Tornai, C.S. Levin, E.J. Hoffman. 1996; 380: 295-300
Removal of the effect of compton scattering in 3-D whole body positron emission tomography by Monte Carlo 1995 IEEE Nuclear Science Symposium and Medical Imaging Conference Levin, C. S., Tai, Y. C., Hoffman, E. J., Dahlbom, M., Farquhar, T. H. IEEE. 1996: 1050–1054
View details for Web of Science ID A1996BF95Z00236
Design considerations and initial performance of a 1.2cm(2) beta imaging intra-operative probe 1995 IEEE Nuclear Science Symposium and Medical Imaging Conference Tornai, M. P., MacDonald, L. R., Levin, C. S., Siegel, S., Hoffman, E. J. IEEE. 1996: 1791–1795
View details for Web of Science ID A1996BF95Z00392
Compton scatter and x-ray crosstalk and the use of very thin inter-crystal septa in high resolution pet detectors 1995 IEEE Nuclear Science Symposium and Medical Imaging Conference Levin, C. S., Tornai, M. P., Cherry, S. R., MacDonald, L. R., Hoffman, E. J. IEEE. 1996: 1036–1040
View details for Web of Science ID A1996BF95Z00233
Characterization of fluor concentration and geometry in organic scintillators for in situ beta imaging 1995 IEEE Nuclear Science Symposium and Medical Imaging Conference Tornai, M. P., Hoffman, E. J., MacDonald, L. R., Levin, C. S. IEEE. 1996: 1632–1636
View details for Web of Science ID A1996BF95Z00359
Optimizing light collection from thin scintillators used in a beta-ray camera for surgical use 1995 IEEE Nuclear Science Symposium and Medical Imaging Conference Levin, C. S., MacDonald, L. R., Tornai, M. P., Hoffman, E. J., Park, J. IEEE. 1996: 1796–1800
View details for Web of Science ID A1996BF95Z00393
Miniature Nuclear Emission Imaging System for Intra-Operative Applications. In: Proceedings from UCLA International Conference on Imaging Detectors in High Energy & Astroparticle Physics M.P. Tornai, L.R. MacDonald, C.S. Levin, S. Siegel, E.J. Hoffman, J. Park, M. Atac, D.B. Cline. 1996: 133-47
Characterization of Fluor Concentration and Geometry in Organic Scintillators for in situ Beta Imaging. IEEE Transactions on Nuclear Science, M.P. Tornai, E.J. Hoffman, C.S. Levin, L.R. MacDonald. 1996; 43-6(2): 3342-47
Design Considerations and Initial Performance of a 1.2 cm2 Beta Imaging Intra-Operative Probe. IEEE Transactions on Nuclear Science, M.P. Tornai, L.R. MacDonald, C.S. Levin, S. Siegel, E.J. Hoffman. 1996; 43-4(1): 2326-2335
Optimizing Light Collection from Thin Scintillators Used in a Beta-Ray Camera for Surgical Use. IEEE Transactions on Nuclear Science, C.S. Levin, L.R. MacDonald, M.P. Tornai, E.J. Hoffman, J. Park. 1996; 43-3(2),: 2053-60
DEVELOPMENT OF A MERCURIC IODIDE DETECTOR ARRAY FOR MEDICAL IMAGING APPLICATIONS NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT Patt, B. E., Iwanczyk, J. S., Tornai, M. P., Levin, C. S., Hoffman, E. J. 1995; 366 (1): 173-182
View details for Web of Science ID A1995TG30900023
INVESTIGATION OF THE PHYSICAL ASPECTS OF BETA-IMAGING PROBES USING SCINTILLATING FIBERS AND VISIBLE-LIGHT PHOTON COUNTERS 1994 Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC) MacDonald, L. R., Tornai, M. P., Levin, C. S., Park, J., Atac, M., Cline, D. B., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1995: 1351–57
View details for Web of Science ID A1995RP81900195
A MONTE-CARLO CORRECTION FOR THE EFFECT OF COMPTON-SCATTERING IN 3-D PET BRAIN IMAGING 1994 Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC) Levin, C. S., Dahlbom, M., Hoffman, E. J. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1995: 1181–85
View details for Web of Science ID A1995RP81900173
A COMPARISON OF PET DETECTOR MODULES EMPLOYING RECTANGULAR AND ROUND PHOTOMULTIPLIER TUBES 1994 Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC) Cherry, S. R., Tornai, M. P., Levin, C. S., Siegel, S., Hoffman, E. J., Andreaco, M. S., Williams, C. W. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 1995: 1064–68
View details for Web of Science ID A1995RP81900154
A Monte Carlo Correction for the Effect of Compton Scattering in 3-D PET Brain Imaging. . IEEE Transactions on Nuclear Science, C.S. Levin, M. Dahlbom, E.J. Hoffman. 1995; 42-4(1, 2): 1181-1185
Small area, fiber coupled scintillation camera for imaging beta-ray distributions intra-operatively Conference on Photoelectronic Detectors, Cameras, and Systems MacDonald, L. R., Tornai, M. P., Levin, C. S., Park, J., Atac, M., Cline, D. B., Hoffman, E. J. SPIE - INT SOC OPTICAL ENGINEERING. 1995: 92–101
View details for Web of Science ID A1995BE06Y00009
Small Area, Fiber Coupled Scintillation Camera for Imaging Beta-Ray Distributions Intra-Operatively. In: Photoelectronic Detectors, Cameras and Systems, Eds. C.B. Johnson, E.J. Fenyves, Proceedings of SPIE, the International Society for Optical Engineering, SPIE, Bellingham, WA. L.R. MacDonald, M.P. Tornai, C.S. Levin, J. Park, M. Atac, D.B. Cline, E.J. Hoffman. 1995; 2551: 92-101
Development of a Mercuric Iodide Detector Array for Medical Imaging Applications. Nuclear Instruments and Methods in Physics Research A, B.E. Patt, J.S. Iwanczyk, M.P. Tornai, C.S. Levin, E.J. Hoffman 1995; 42-4(1, 2): 1181-1185
A Comparison of PET Detector Modules Employing Rectangular and Round Photomultiplier Tubes. IEEE Transactions on Nuclear Science, S. R. Cherry, M.P. Tornai, C.S. Levin, S. Siegel, E.J. Hoffman. 1995; 42-4(1, 2): 1064-1068
Investigation of the Physical Aspects of Beta Imaging Probes Using Scintillating Fibers and Visible Light Photon Counters. IEEE Transactions on Nuclear Science, L.R. MacDonald, M.P. Tornai, C.S. Levin, J. Park, M. Atac, D.B. Cline, E.J Hoffman. 1995; 42-4(1, 2): 1351-1357
Development of a Mercuric Iodide Detector Array for in-vivo X-Ray Imaging. Advances in X-Ray Analysis, B.E. Patt, J.S. Iwanczyk, M.P. Tornai, C.S. Levin, E.J. Hoffman. 1995; 38: 615-24
Investigation of the physical aspects of beta imaging probes using scintillating fibers and visible light photon counters 1994 Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC) MacDonald, L. R., Tornai, M. P., Levin, C. S., Park, J., Atac, M., Cline, D. B., Hoffman, E. J. I E E E. 1994: 1380–1384
View details for Web of Science ID A1994BD85P00284
A Monte Carlo correction for compton scattering effects in 3D pet brain imaging 1994 Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC) Levin, C. S., Dahlbom, M., Hoffman, E. J. I E E E. 1994: 1502–1506
View details for Web of Science ID A1994BD85P00311

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

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