Publications by authors named "Yuan-Chuan Tai"

40 Publications

Small-Animal PET: A Technology That Changed Our Field.

Authors:
Yuan-Chuan Tai

J Nucl Med 2020 12;61(Suppl 2):153S-154S

Washington University, St. Louis, Missouri

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http://dx.doi.org/10.2967/jnumed.120.251280DOI Listing
December 2020

Seasonal nitrogen remobilization and the role of auxin transport in poplar trees.

J Exp Bot 2020 Jul;71(15):4512-4530

Department of Plant Science and Landscape Architecture, University of Maryland, College Park, USA.

Seasonal nitrogen (N) cycling in Populus, involves bark storage proteins (BSPs) that accumulate in bark phloem parenchyma in the autumn and decline when shoot growth resumes in the spring. Little is known about the contribution of BSPs to growth or the signals regulating N remobilization from BSPs. Knockdown of BSP accumulation via RNAi and N sink manipulations were used to understand how BSP storage influences shoot growth. Reduced accumulation of BSPs delayed bud break and reduced shoot growth following dormancy. Further, 13N tracer studies also showed that BSP accumulation is an important factor in N partitioning from senescing leaves to bark. Thus, BSP accumulation has a role in N remobilization during N partitioning both from senescing leaves to bark and from bark to expanding shoots once growth commences following dormancy. The bark transcriptome during BSP catabolism and N remobilization was enriched in genes associated with auxin transport and signaling, and manipulation of the source of auxin or auxin transport revealed a role for auxin in regulating BSP catabolism and N remobilization. Therefore, N remobilization appears to be regulated by auxin produced in expanding buds and shoots that is transported to bark where it regulates protease gene expression and BSP catabolism.
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http://dx.doi.org/10.1093/jxb/eraa130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382381PMC
July 2020

Augmented Whole-Body Scanning via Magnifying PET.

IEEE Trans Med Imaging 2020 Nov 28;39(11):3268-3277. Epub 2020 Oct 28.

A novel technique, called augmented whole-body scanning via magnifying PET (AWSM-PET), that improves the sensitivity and lesion detectability of a PET scanner for whole-body imaging is proposed and evaluated. A Siemens Biograph Vision PET/CT scanner equipped with one or two high-resolution panel-detectors was simulated to study the effectiveness of AWSM-PET technology. The detector panels are located immediately outside the scanner's axial field-of-view (FOV). A detector panel contains 2 ×8 detector modules each consisting of 32 ×64 LSO crystals ( 1.0 ×1.0 ×10.0 mm each). A Na point source was stepped across the scanner's FOV axially to measure sensitivity profiles at different locations. An elliptical torso phantom containing 7×9 spherical lesions was imaged at different axial locations to mimic a multi-bed-position whole-body imaging protocol. Receiver operating characteristic (ROC) curves were analyzed to evaluate the improvement in lesion detectability by the AWSM-PET technology. Experimental validation was conducted using an existing flat-panel detector integrated with a Siemens Biograph 40 PET/CT scanner to image a torso phantom containing spherical lesions with diameters ranging from 3.3 to 11.4 mm. The contrast-recovery-coefficient (CRC) of the lesions was evaluated for the scanner with or without the AWSM-PET technology. Monte Carlo simulation shows 36%-42% improvement in system sensitivity by a dual-panel AWSM-PET device. The area under the ROC curve is 0.962 by a native scanner for the detection of 4 mm diameter lesions with 5:1 tumor-to-background activity concentration. It was improved to 0.977 and 0.991 with a single- and dual-panel AWSM-PET system, respectively. Experimental studies showed that the average CRC of 3.3 mm and 4.3 mm diameter tumors were improved from 2.8% and 4.2% to 7.9% and 11.0%, respectively, by a single-panel AWSM-PET device. With a high-sensitivity dual-panel device, the corresponding CRC can be further improved to 11.0% and 15.9%, respectively. The principle of the AWSM-PET technology has been developed and validated. Enhanced system sensitivity, CRC and tumor detectability were demonstrated by Monte Carlo simulations and imaging experiments. This technology may offer a cost-effective path to realize high-resolution whole-body PET imaging clinically.
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http://dx.doi.org/10.1109/TMI.2019.2962623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673659PMC
November 2020

A second-generation virtual-pinhole PET device for enhancing contrast recovery and improving lesion detectability of a whole-body PET/CT scanner.

Med Phys 2019 Sep 7;46(9):4165-4176. Epub 2019 Aug 7.

Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.

Purpose: We have developed a second-generation virtual-pinhole (VP) positron emission tomography (PET) device that can position a flat-panel PET detector around a patient's body using a robotic arm to enhance the contrast recovery coefficient (CRC) and detectability of lesions in any region-of-interest using a whole-body PET/computed tomography (CT) scanner.

Methods: We constructed a flat-panel VP-PET device using 32 high-resolution detectors, each containing a 4   4 MPPC array and 16   16 LYSO crystals of 1.0   1.0   3.0 mm each. The flat-panel detectors can be positioned around a patient's body anywhere in the imaging field-of-view (FOV) of a Siemens Biograph 40 PET/CT scanner by a robotic arm. New hardware, firmware and software have been developed to support the additional detector signals without compromising a scanner's native functions. We stepped a Na point source across the axial FOV of the scanner to measure the sensitivity profile of the VP-PET device. We also recorded the coincidence events measured by the scanner detectors and by the VP-PET detectors when imaging phantoms of different sizes. To assess the improvement in the CRC of small lesions, we imaged an elliptical torso phantom measuring 316   228   162 mm that contains spherical tumors with diameters ranging from 3.3 to 11.4 mm with and without the VP-PET device. Images were reconstructed using a list mode Maximum-Likelihood Estimation-Maximization algorithm implemented on multiple graphics processing units (GPUs) to support the unconventional geometries enabled by a VP-PET system. The mean and standard deviation of the CRC were calculated for tumors of different sizes. Monte Carlo simulation was also conducted to image clusters of lesions in a torso phantom using a PET/CT scanner alone or the same scanner equipped with VP-PET devices. Receiver operating characteristic (ROC) curves were analyzed for three system configurations to evaluate the improvement in lesion detectability by the VP-PET device over the native PET/CT scanner.

Results: The repeatability in positioning the flat-panel detectors using a robotic arm is better than 0.15 mm in all three directions. Experimental results show that the average CRC of 3.3, 4.3, and 6.0 mm diameter tumors was 0.82%, 2.90%, and 5.25%, respectively, when measured by the native scanner. The corresponding CRC was 2.73%, 6.21% and 10.13% when imaged by the VP-PET insert device with the flat-panel detector under the torso phantom. These values may be further improved to 4.31%, 9.65% and 18.01% by a future dual-panel VP-PET insert device if DOI detectors are employed to triple its detector efficiency. Monte Carlo simulation results show that the tumor detectability can be improved by a VP-PET device that has a single flat-panel detector. The improvement is greater if the VP-PET device employs a dual-panel design.

Conclusions: We have developed a prototype flat-panel VP-PET device and integrated it with a clinical PET/CT scanner. It significantly enhances the contrast of lesions, especially for those that are borderline detectable by the native scanner, within regions-of-interest specified by users. Simulation demonstrated the enhancement in lesion detectability with the VP-PET device. This technology may become a cost-effective solution for organ-specific imaging tasks.
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http://dx.doi.org/10.1002/mp.13724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739194PMC
September 2019

Cherenkov luminescence imaging of shallow sources in semitransparent media.

J Biomed Opt 2019 02;24(2):1-9

Washington University in St. Louis, Department of Radiology, St. Louis, Missouri, United States.

We experimentally investigated the Cherenkov luminescence imaging (CLI) of the isotopes with different beta particles energies (Cu64, F18, Au198, P32, and Br76) in semitransparent biological equivalent media. The main focus of this work is to characterize the CLI when the sources are at the depth comparable with the range of beta particles. The experimental results were compared with Monte Carlo (MC) simulation results to fine tune the simulation parameters to better model the phantom materials. This approach can be applied to estimate the CLI performance for different phantom materials and isotopes. This work also demonstrates some unique properties of high energy beta particles that can be beneficial for CLI, including the possibility to utilize the betas escaped from the object for imaging purposes.
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http://dx.doi.org/10.1117/1.JBO.24.2.026001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988091PMC
February 2019

Feasibility study of a point-of-care positron emission tomography system with interactive imaging capability.

Med Phys 2019 Apr 14;46(4):1798-1813. Epub 2019 Feb 14.

Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MI, 63110, USA.

Purpose: We investigated the feasibility of a novel positron emission tomography (PET) system that provides near real-time feedback to an operator who can interactively scan a patient to optimize image quality. The system should be compact and mobile to support point-of-care (POC) molecular imaging applications. In this study, we present the key technologies required and discuss the potential benefits of such new capability.

Methods: The core of this novel PET technology includes trackable PET detectors and a fully three-dimensional, fast image reconstruction engine implemented on multiple graphics processing units (GPUs) to support dynamically changing geometry by calculating the system matrix on-the-fly using a tube-of-response approach. With near real-time image reconstruction capability, a POC-PET system may comprise a maneuverable front PET detector and a second detector panel which can be stationary or moved synchronously with the front detector such that both panels face the region-of-interest (ROI) with the detector trajectory contoured around a patient's body. We built a proof-of-concept prototype using two planar detectors each consisting of a photomultiplier tube (PMT) optically coupled to an array of 48 × 48 lutetium-yttrium oxyorthosilicate (LYSO) crystals (1.0 × 1.0 × 10.0 mm each). Only 38 × 38 crystals in each arrays can be clearly re-solved and used for coincidence detection. One detector was mounted to a robotic arm which can position it at arbitrary locations, and the other detector was mounted on a rotational stage. A cylindrical phantom (102 mm in diameter, 150 mm long) with nine spherical lesions (8:1 tumor-to-background activity concentration ratio) was imaged from 27 sampling angles. List-mode events were reconstructed to form images without or with time-of-flight (TOF) information. We conducted two Monte Carlo simulations using two POC-PET systems. The first one uses the same phantom and detector setup as our experiment, with the detector coincidence re-solving time (CRT) ranging from 100 to 700 ps full-width-at-half-maximum (FWHM). The second study simulates a body-size phantom (316 × 228 × 160 mm ) imaged by a larger POC-PET system that has 4 × 6 modules (32 × 32 LYSO crystals/module, four in axial and six in transaxial directions) in the front panel and 3 × 8 modules (16 × 16 LYSO crystals/module, three in axial and eight in transaxial directions) in the back panel. We also evaluated an interactive scanning strategy by progressively increasing the number of data sets used for image reconstruction. The updated images were analyzed based on the number of data sets and the detector CRT.

Results: The proof-of-concept prototype re-solves most of the spherical lesions despite a limited number of coincidence events and incomplete sampling. TOF information reduces artifacts in the reconstructed images. Systems with better timing resolution exhibit improved image quality and reduced artifacts. We observed a reconstruction speed of 0.96 × 10 events/s/iteration for 600 × 600 × 224 voxel rectilinear space using four GPUs. A POC-PET system with significantly higher sensitivity can interactively image a body-size object from four angles in less than 7 min.

Conclusions: We have developed GPU-based fast image reconstruction capability to support a PET system with arbitrary and dynamically changing geometry. Using TOF PET detectors, we demonstrated the feasibility of a PET system that can provide timely visual feedback to an operator who can scan a patient interactively to support POC imaging applications.
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http://dx.doi.org/10.1002/mp.13397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453727PMC
April 2019

Focused ultrasound combined with microbubble-mediated intranasal delivery of gold nanoclusters to the brain.

J Control Release 2018 09 26;286:145-153. Epub 2018 Jul 26.

Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130, USA; Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO 63108, USA. Electronic address:

Focused ultrasound combined with microbubble-mediated intranasal delivery (FUSIN) is a new brain drug delivery technique. FUSIN utilizes the nasal route for direct nose-to-brain drug administration, thereby bypassing the blood-brain barrier (BBB) and minimizing systemic exposure. It also uses FUS-induced microbubble cavitation to enhance transport of intranasally (IN) administered agents to the FUS-targeted brain location. Previous studies have provided proof-of-concept data showing the feasibility of FUSIN to deliver dextran and the brain-derived neurotrophic factor to the caudate putamen of mouse brains. The objective of this study was to evaluate the biodistribution of IN administered gold nanoclusters (AuNCs) and assess the feasibility and short-term safety of FUSIN for the delivery of AuNCs to the brainstem. Three experiments were performed. First, the whole-body biodistribution of IN administered Cu-alloyed AuNCs (Cu-AuNCs) was assessed using in vivo positron emission tomography/computed tomography (PET/CT) and verified with ex vivo gamma counting. Control mice were intravenously (IV) injected with the Cu-AuNCs. Second, Cu-AuNCs and Texas red-labeled AuNCs (TR-AuNCs) were used separately to evaluate FUSIN delivery outcome in the brain. Cu-AuNCs or TR-AuNCs were administered to mice through the nasal route, followed by FUS sonication at the brainstem in the presence of systemically injected microbubbles. The spatial distribution of Cu-AuNCs and TR-AuNCs were examined by autoradiography and fluorescence microscopy of ex vivo brain slices, respectively. Third, histological analysis was performed to evaluate any potential histological damage to the nose and brain after FUSIN treatment. The experimental results revealed that IN administration induced significantly lower Cu-AuNCs accumulation in the blood, lungs, liver, spleen, kidney, and heart compared with IV injection. FUSIN enhanced the delivery of Cu-AuNCs and TR-AuNCs at the FUS-targeted brain region compared with IN delivery alone. No histological-level tissue damage was detected in the nose, trigeminal nerve, and brain. These results suggest that FUSIN is a promising technique for noninvasive, spatially targeted, and safe delivery of nanoparticles to the brain with minimal systemic exposure.
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http://dx.doi.org/10.1016/j.jconrel.2018.07.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138562PMC
September 2018

Focused Ultrasound Enabled Trans-Blood Brain Barrier Delivery of Gold Nanoclusters: Effect of Surface Charges and Quantification Using Positron Emission Tomography.

Small 2018 07 2;14(30):e1703115. Epub 2018 Jul 2.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Focused ultrasound (FUS) technology is reported to enhance the delivery of Cu-integrated ultrasmall gold nanoclusters ( Cu-AuNCs) across the blood-brain barrier (BBB) as measured by positron emission tomography (PET). To better define the optimal physical properties for brain delivery, Cu-AuNCs with different surface charges are synthesized and characterized. In vivo biodistribution studies are performed to compare the individual organ uptake of each type of Cu-AuNCs. Quantitative PET imaging post-FUS treatment shows site-targeted brain penetration, retention, and diffusion of the negative, neutral, and positive Cu-AuNCs. Autoradiography is performed to compare the intrabrain distribution of these nanoclusters. PET Imaging demonstrates the effective BBB opening and successful delivery of Cu-AuNCs into the brain. Of the three Cu-AuNCs investigated, the neutrally charged nanostructure performs the best and is the candidate platform for future theranostic applications in neuro-oncology.
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http://dx.doi.org/10.1002/smll.201703115DOI Listing
July 2018

Focused ultrasound-enabled delivery of radiolabeled nanoclusters to the pons.

J Control Release 2018 08 1;283:143-150. Epub 2018 Jun 1.

Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130, USA; Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO 63108, USA. Electronic address:

The goal of this study was to establish the feasibility of integrating focused ultrasound (FUS)-mediated delivery of Cu-integrated gold nanoclusters (Cu-AuNCs) to the pons for in vivo quantification of the nanocluster brain uptake using positron emission tomography (PET) imaging. FUS was targeted at the pons for the blood-brain barrier (BBB) disruption in the presence of systemically injected microbubbles, followed by the intravenous injection of Cu-AuNCs. The spatiotemporal distribution of the Cu-AuNCs in the brain was quantified using in vivo microPET/CT imaging at different time points post injection. Following PET imaging, the accumulation of radioactivity in the pons was further confirmed using autoradiography and gamma counting, and the gold concentration was quantified using inductively coupled plasma-mass spectrometry (ICP-MS). We found that the noninvasive and localized BBB opening by the FUS successfully delivered the Cu-AuNCs to the pons. We also demonstrated that in vivo real-time microPET/CT imaging was a reliable method for monitoring and quantifying the brain uptake of Cu-AuNCs delivered by the FUS. This drug delivery platform that integrates FUS, radiolabeled nanoclusters, and PET imaging provides a new strategy for noninvasive and localized nanoparticle delivery to the pons with concurrent in vivo quantitative imaging to evaluate delivery efficiency. The long-term goal is to apply this drug delivery platform to the treatment of pontine gliomas.
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http://dx.doi.org/10.1016/j.jconrel.2018.05.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035767PMC
August 2018

Penetration depth of photons in biological tissues from hyperspectral imaging in shortwave infrared in transmission and reflection geometries.

J Biomed Opt 2016 12;21(12):126006

Washington University School of Medicine, Department of Radiology, St. Louis, Missouri, United States.

Measurement of photon penetration in biological tissues is a central theme in optical imaging. A great number of endogenous tissue factors such as absorption, scattering, and anisotropy affect the path of photons in tissue, making it difficult to predict the penetration depth at different wavelengths. Traditional studies evaluating photon penetration at different wavelengths are focused on tissue spectroscopy that does not take into account the heterogeneity within the sample. This is especially critical in shortwave infrared where the individual vibration-based absorption properties of the tissue molecules are affected by nearby tissue components. We have explored the depth penetration in biological tissues from 900 to 1650 nm using Monte–Carlo simulation and a hyperspectral imaging system with Michelson spatial contrast as a metric of light penetration. Chromatic aberration-free hyperspectral images in transmission and reflection geometries were collected with a spectral resolution of 5.27 nm and a total acquisition time of 3 min. Relatively short recording time minimized artifacts from sample drying. Results from both transmission and reflection geometries consistently revealed that the highest spatial contrast in the wavelength range for deep tissue lies within 1300 to 1375 nm; however, in heavily pigmented tissue such as the liver, the range 1550 to 1600 nm is also prominent.
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http://dx.doi.org/10.1117/1.JBO.21.12.126006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147011PMC
December 2016

A simultaneous beta and coincidence-gamma imaging system for plant leaves.

Phys Med Biol 2016 May 11;61(9):3572-95. Epub 2016 Apr 11.

Department of Electrical and Systems Engineering, Washington University in St. Louis, MO, USA.

Positron emitting isotopes, such as (11)C, (13)N, and (18)F, can be used to label molecules. The tracers, such as (11)CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have a higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to poor positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (simultaneous beta-gamma imager). The imager can simultaneously detect positrons ([Formula: see text]) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs beta and gamma images independently to estimate the thickness component of the beta forward model and afterward jointly estimates the radioactivity distribution in the object. We have validated the physics model and reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed (11)CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the structural similarity (SSIM) index for comparing the leaf images from the simultaneous beta-gamma imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively.
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http://dx.doi.org/10.1088/0031-9155/61/9/3572DOI Listing
May 2016

Biodistribution and Radiation Dosimetry of the Enterobacteriaceae-Specific Imaging Probe [(18)F]Fluorodeoxysorbitol Determined by PET/CT in Healthy Human Volunteers.

Mol Imaging Biol 2016 10;18(5):782-7

Department of Nuclear Medicine, Peking Union Medical College Hospital, 1# Shuaifuyuan, Dongcheng District, Beijing, China.

Purpose: [(18)F]fluorodeoxysorbitol ([(18)F]FDS) is the first radiopharmaceutical specific for a category of bacteria and has the potential to specifically detect Enterobacteriaceae infections. The purpose of this study was to testify the safety and investigate the biodistribution and radiation dosimetry of [(18)F]FDS in healthy human bodies.

Procedures: Six healthy subjects were intravenously injected with 320-520 MBq [(18)F]FDS. On each subject, 21 whole-body emission scans and a brain scan were conducted at settled time points within the next 4 h. Residence time for each source organ was determined by multi-exponential regression. Absorbed doses for target organs and effective dose were calculated via OLINDA/EXM.

Results: No adverse events due to [(18)F]FDS injection were observed in the study. The tracer was cleared rapidly from the blood pool through the urinary system. A small portion was cleared into the gut through the hepatobiliary system. The effective dose (ED) was estimated to be 0.021 ± 0.001 mSv/MBq. The organ receiving the highest absorbed dose was the urinary bladder wall (0.25 ± 0.03 mSv/MBq).

Conclusions: [(18)F]FDS is safe and well tolerated. The effective dose was comparable to that of other F-18 labeled radiotracers. [(18)F]FDS is suitable for human use from a radiation dosimetry perspective.
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http://dx.doi.org/10.1007/s11307-016-0946-9DOI Listing
October 2016

A generalized reconstruction framework for unconventional PET systems.

Med Phys 2015 Aug;42(8):4591-609

Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri 63110.

Purpose: Quantitative estimation of the radionuclide activity concentration in positron emission tomography (PET) requires precise modeling of PET physics. The authors are focused on designing unconventional PET geometries for specific applications. This work reports the creation of a generalized reconstruction framework, capable of reconstructing tomographic PET data for systems that use right cuboidal detector elements positioned at arbitrary geometry using a regular Cartesian grid of image voxels.

Methods: The authors report on a variety of design choices and optimization for the creation of the generalized framework. The image reconstruction algorithm is maximum likelihood-expectation-maximization. System geometry can be specified using a simple script. Given the geometry, a symmetry seeking algorithm finds existing symmetry in the geometry with respect to the image grid to improve the memory usage/speed. Normalization is approached from a geometry independent perspective. The system matrix is computed using the Siddon's algorithm and subcrystal approach. The program is parallelized through open multiprocessing and message passing interface libraries. A wide variety of systems can be modeled using the framework. This is made possible by modeling the underlying physics and data correction, while generalizing the geometry dependent features.

Results: Application of the framework for three novel PET systems, each designed for a specific application, is presented to demonstrate the robustness of the framework in modeling PET systems of unconventional geometry. Three PET systems of unconventional geometry are studied. (1) Virtual-pinhole half-ring insert integrated into Biograph-40: although the insert device improves image quality over conventional whole-body scanner, the image quality varies depending on the position of the insert and the object. (2) Virtual-pinhole flat-panel insert integrated into Biograph-40: preliminary results from an investigation into a modular flat-panel insert are presented. (3) Plant PET system: a reconfigurable PET system for imaging plants, with resolution of greater than 3.3 mm, is shown. Using the automated symmetry seeking algorithm, the authors achieved a compression ratio of the storage and memory requirement by a factor of approximately 50 for the half-ring and flat-panel systems. For plant PET system, the compression ratio is approximately five. The ratio depends on the level of symmetry that exists in different geometries.

Conclusions: This work brings the field closer to arbitrary geometry reconstruction. A generalized reconstruction framework can be used to validate multiple hypotheses and the effort required to investigate each system is reduced. Memory usage/speed can be improved with certain optimizations.
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http://dx.doi.org/10.1118/1.4923180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506302PMC
August 2015

A compact high resolution flat panel PET detector based on the new 4-side buttable MPPC for biomedical applications.

Nucl Instrum Methods Phys Res A 2015 Sep;794:151-159

Washington University in St Louis, MO 63110, USA.

Compact high-resolution panel detectors using virtual pinhole (VP) PET geometry can be inserted into existing clinical or pre-clinical PET systems to improve regional spatial resolution and sensitivity. Here we describe a compact panel PET detector built using the new Though Silicon Via (TSV) multi-pixel photon counters (MPPC) detector. This insert provides high spatial resolution and good timing performance for multiple bio-medical applications. Because the TSV MPPC design eliminates wire bonding and has a package dimension which is very close to the MPPC's active area, it is 4-side buttable. The custom designed MPPC array (based on Hamamatsu S12641-PA-50(x)) used in the prototype is composed of 4 × 4 TSV-MPPC cells with a 4.46 mm pitch in both directions. The detector module has 16 × 16 lutetium yttrium oxyorthosilicate (LYSO) crystal array, with each crystal measuring 0.92 × 0.92 × 3 mm with 1.0 mm pitch. The outer diameter of the detector block is 16.8 × 16.8 mm. Thirty-two such blocks will be arranged in a 4 × 8 array with 1 mm gaps to form a panel detector with detection area around 7 cm × 14 cm in the full-size detector. The flood histogram acquired with Ge-68 source showed excellent crystal separation capability with all 256 crystals clearly resolved. The detector module's mean, standard deviation, minimum (best) and maximum (worst) energy resolution were 10.19%, +/-0.68%, 8.36% and 13.45% FWHM, respectively. The measured coincidence time resolution between the block detector and a fast reference detector (around 200 ps single photon timing resolution) was 0.95 ns. When tested with Siemens Cardinal electronics the performance of the detector blocks remain consistent. These results demonstrate that the TSV-MPPC is a promising photon sensor for use in a flat panel PET insert composed of many high resolution compact detector modules.
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http://dx.doi.org/10.1016/j.nima.2015.04.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465487PMC
September 2015

Cherenkov luminescence imaging in transparent media and the imaging of thin or shallow sources.

J Biomed Opt 2015 03;20(3):036011

In this work, we demonstrated the possibility of high spatial resolution Cherenkov luminescence imaging (CLI) for objects in transparent media. We also demonstrated the possibility of the CLI of thin opaque objects using optical transducers. Results demonstrate that submillimeter resolution CLI is achievable for beta-emitting radionuclides, including ⁷⁶Br that emits positrons of very high energy. The imaging of beta-emitters through scintillation detectors exhibits lower resolution when compared to CLI of the same sources. The application of optical transducers for the CLI was demonstrated using plants labeled with ¹¹CO₂ and phantoms containing beta-emitters.
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http://dx.doi.org/10.1117/1.JBO.20.3.036011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365802PMC
March 2015

A dedicated high-resolution PET imager for plant sciences.

Phys Med Biol 2014 Oct 5;59(19):5613-29. Epub 2014 Sep 5.

Department of Radiology, Washington University in St Louis, MO 63110, USA.

PET provides an in vivo molecular and functional imaging capability that could be valuable for studying the interaction of plants in changing environments at the whole-plant level. We have developed a dedicated plant PET imager housed in a plant growth chamber (PGC), which provides a fully controlled environment. The system currently contains two types of scintillation detector modules from commercial small animal PET scanners: 84 microPET® detectors, which are made with scintillation crystal arrays of 2.2 mm(3) × 2.2 mm(3) × 10 mm(3) crystals to provide a large detection area; and 32 Inveon™ detectors, which are made with scintillation crystal arrays of 1.5 mm(3) × 1.5 mm(3) × 10 mm(3) crystals to provide higher spatial resolution. The detector modules are configured to form two half-rings, which provide a 15 cm-diameter trans-axial field of view (FOV) for dynamic tomographic imaging of small plants. Alternatively, the Inveon detectors can be reconfigured to form quarter-rings, which provide a 25 cm FOV using step-and-shoot motion. The imager contains two linear stages that move detectors vertically at different heights for multisection scanning, and two rotation stages to collect coincidence events from all angles when using the step-and-shoot acquisition. The detector modules and mechanical components of the imager are housed inside a PGC that regulates the environmental parameters. The system has a typical energy resolution of 15% for the Inveon detectors and 24% for the microPET detectors, timing resolution of 1.8 ns, and sensitivity of 1.3%, 1.4% and 3.0% measured at the center of the FOV, 5 cm off to the larger half-ring and 5 cm off to the smaller half-ring, respectively (with a 350-650 keV energy window and 3.1 ns timing window). The system's spatial resolution is capable of resolving rod sources of 1.25 mm diameter spaced 2.5 mm apart (center to center) using the ML-EM reconstruction algorithm. Preliminary imaging experiments using soybean and wild type and mutant maize labeled with (11)CO2 produced high-quality dynamic PET images that reveal the translocation and distribution patterns of photoassimilates. This system can be used to provide an in vivo molecular and functional imaging capability for plant research.
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http://dx.doi.org/10.1088/0031-9155/59/19/5613DOI Listing
October 2014

Improving PET imaging for breast cancer using virtual pinhole PET half-ring insert.

Phys Med Biol 2013 Sep 2;58(18):6407-27. Epub 2013 Sep 2.

Department of Electrical and Systems Engineering, Washington University in St Louis, MO 63130, USA.

A PET insert with detector having smaller crystals and placed near a region of interest in a conventional PET scanner can improve image resolution locally due to the virtual-pinhole PET (VP-PET) effect. This improvement is from the higher spatial sampling of the imaging area near the detector. We have built a prototype half-ring PET insert for head-and-neck cancer imaging applications. In this paper, we extend the use of the insert to breast imaging and show that such a system provides high resolution images of breast and axillary lymph nodes while maintaining the full imaging field of view capability of a clinical PET scanner. We characterize the resolution and contrast recovery for tumors across the imaging field of view. First, we model the system using Monte Carlo methods to determine its theoretical limit of improvement. Simulations were conducted with hot spherical tumors embedded in background activity at tumor-to-background contrast ranging from 3:1 to 12:1. Tumors are arranged in a Derenzo-like pattern with their diameters ranging from 2 to 12 mm. Experimental studies were performed using a chest phantom with cylindrical breast attachment. Tumors of different sizes arranged in a Derenzo-like pattern with tumor-to-background ratio of 6:1 are inserted into the breast phantom. Imaging capability of mediastinum and axillary lymph nodes is explored. Both Monte Carlo simulations and experiment show clear improvement in image resolution and contrast recovery with VP-PET half-ring insert. The degree of improvement in resolution and contrast recovery depends on location of the tumor. The full field of view imaging capability is shown to be maintained. Minor artifacts are introduced in certain regions.
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http://dx.doi.org/10.1088/0031-9155/58/18/6407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890243PMC
September 2013

Multimodal fluorescence-mediated tomography and SPECT/CT for small-animal imaging.

J Nucl Med 2013 Apr 27;54(4):639-46. Epub 2013 Feb 27.

Department of Biomedical Engineering, Washington University, St. Louis, MO 63110, USA.

Unlabelled: Spatial and temporal coregistration of nuclear and optical images can enable the fusion of the information from these complementary molecular imaging modalities. A critical challenge is in integrating the optical and nuclear imaging hardware. Flexible fiber-based fluorescence-mediated tomography (FMT) systems provide a viable solution. The various bore sizes of small-animal nuclear imaging systems can potentially accommodate the FMT fiber imaging arrays. In addition, FMT imaging facilitates coregistration of the nuclear and optical contrasts in time. Herein, we combine a fiber-based FMT system with a preclinical SPECT/CT platform. Feasibility of in vivo imaging is demonstrated by tracking a monomolecular multimodal imaging agent (MOMIA) during transport from the forepaw to the axillary lymph node region of a rat.

Methods: The fiber-based, video-rate FMT imaging system is composed of 12 sources (785- and 830-nm laser diodes) and 13 detectors. To maintain high temporal sampling, the system simultaneously acquires ratio-metric data at each detector. A 3-dimensional finite element model derived from CT projections provides anatomically based light propagation modeling. Injection of a MOMIA intradermally into the forepaw of rats provided spatially and temporally coregistered nuclear and optical contrasts. FMT data were acquired concurrently with SPECT and CT data. The incorporation of SPECT data as a priori information in the reconstruction of FMT data integrated both optical and nuclear contrasts.

Results: Accurate depth localization of phantoms with different thicknesses was accomplished with an average center-of-mass error of 4.1 ± 2.1 mm between FMT and SPECT measurements. During in vivo tests, fluorescence and radioactivity from the MOMIA were colocalized in spatially coincident regions with an average center-of-mass error of 2.68 ± 1.0 mm between FMT and SPECT for axillary lymph node localization. Intravital imaging with surgical exposure of the lymph node validated the localization of the optical contrast.

Conclusion: The feasibility of integrating a fiber-based, video-rate FMT system with a commercial preclinical SPECT/CT platform was established. These coregistered FMT and SPECT/CT results with MOMIAs may facilitate the development of the next generation of preclinical and clinical multimodal optical-nuclear platforms for a broad array of imaging applications and help elucidate the underlying biologic processes relevant to cancer diagnosis and therapy monitoring.
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http://dx.doi.org/10.2967/jnumed.112.105742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956308PMC
April 2013

3-D Spatial Resolution of 350 m Pitch Pixelated CdZnTe Detectors for Imaging Applications.

IEEE Trans Nucl Sci 2013 Feb 17;60(1):9-15. Epub 2012 Sep 17.

Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110 USA.

We are currently investigating the feasibility of using highly pixelated Cadmium Zinc Telluride (CdZnTe) detectors for sub-500 m resolution PET imaging applications. A 20 mm × 20 mm × 5 mm CdZnTe substrate was fabricated with 350 m pitch pixels (250 m anode pixels with 100 m gap) and coplanar cathode. Charge sharing among the pixels of a 350 m pitch detector was studied using collimated 122 keV and 511 keV gamma ray sources. For a 350 m pitch CdZnTe detector, scatter plots of the charge signal of two neighboring pixels clearly show more charge sharing when the collimated beam hits the gap between adjacent pixels. Using collimated Co-57 and Ge-68 sources, we measured the count profiles and estimated the intrinsic spatial resolution of 350 m pitch detector biased at -1000 V. Depth of interaction was analyzed based on two methods, i.e., cathode/anode ratio and electron drift time, in both 122 keV and 511 keV measurements. For single-pixel photopeak events, a linear correlation between cathode/anode ratio and electron drift time was shown, which would be useful for estimating the DOI information and preserving image resolution in CdZnTe PET imaging applications.
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http://dx.doi.org/10.1109/TNS.2012.2213611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328192PMC
February 2013

Use of systematic surface roughing to enhance the spatial resolution of the dual-ended readout of axially-oriented 100 mm long LYSO crystals.

Phys Med Biol 2012 Dec 23;57(24):N501-12. Epub 2012 Nov 23.

Department of Physics & Astronomy, University of Manitoba, Winnipeg, Canada.

In this work we explored the effects of using systematic band patterns of surface roughing to modulate the light transport in a dual-ended readout detector for PET imaging that uses 100 mm long LYSO crystals oriented in the axial direction. The long surfaces of 3 × 2 × 100 mm³ LYSO crystals, initially polished on all sides, were systematically roughed in a band pattern with 0.8 mm bands of roughed surface spaced at 5 mm increments over the central 8 cm of the crystal length. Cases of one to four surfaces of the crystal roughed with this pattern were explored. Two configurations of bands were examined for the opposite surfaces of the crystals: (i) bands created in the same axial location (coinciding bands) and (ii) band locations interleaved (interleaving bands). Each crystal was then wrapped in Teflon and read out at both ends using position sensitive photomultiplier tubes (PSPMTs). An electronically collimated 511 keV photon beam was oriented perpendicular to the long direction of the crystal and data acquired at discrete locations along the crystal length. The ratio of the two PMT signals was used to find the axial position of interaction and axial-positioning resolution in the light sharing direction of the dual-ended readout detector while their sum was used to determine the light output and energy resolution. The axial-positioning resolution corrected for the beam width improved from an average of 8.7 mm FWHM with no surface treatment to 5.9, 3.9 or 3.4 mm FWHM for coinciding band patterns on one, two or four surfaces, respectively. The banding patterns resulted in degraded energy resolution, with a decrease from 11.1% FWHM for the untreated crystal to 12.0%, 13.5% and 13.6% for the patterns on one, two and four surfaces, respectively. When the axial-positioning resolution is corrected for the beam width, we estimated the best resolution for the case of four banded surfaces to be 3.4 mm FWHM in this study. The same axial-positioning resolution was obtained when interleaving bands were created on only two opposite surfaces with a better energy resolution of 12.2%.
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http://dx.doi.org/10.1088/0031-9155/57/24/N501DOI Listing
December 2012

Investigation of the limitations of the highly pixilated CdZnTe detector for PET applications.

Phys Med Biol 2012 Nov 18;57(22):7355-80. Epub 2012 Oct 18.

Department of Radiology, Washington University, St. Louis, MO 63110, USA.

We are investigating the feasibility of a high resolution positron emission tomography (PET) insert device based on the CdZnTe detector with 350 µm anode pixel pitch to be integrated into a conventional animal PET scanner to improve its image resolution. In this paper, we have used a simplified version of the multi pixel CdZnTe planar detector, 5 mm thick with 9 anode pixels only. This simplified 9 anode pixel structure makes it possible to carry out experiments without a complete application-specific integrated circuits readout system that is still under development. Special attention was paid to the double pixel (or charge sharing) detections. The following characteristics were obtained in experiment: energy resolution full-width-at-half-maximum (FWHM) is 7% for single pixel and 9% for double pixel photoelectric detections of 511 keV gammas; timing resolution (FWHM) from the anode signals is 30 ns for single pixel and 35 ns for double pixel detections (for photoelectric interactions only the corresponding values are 20 and 25 ns); position resolution is 350 µm in x,y-plane and ∼0.4 mm in depth-of-interaction. The experimental measurements were accompanied by Monte Carlo (MC) simulations to find a limitation imposed by spatial charge distribution. Results from MC simulations suggest the limitation of the intrinsic spatial resolution of the CdZnTe detector for 511 keV photoelectric interactions is 170 µm. The interpixel interpolation cannot recover the resolution beyond the limit mentioned above for photoelectric interactions. However, it is possible to achieve higher spatial resolution using interpolation for Compton scattered events. Energy and timing resolution of the proposed 350 µm anode pixel pitch detector is no better than 0.6% FWHM at 511 keV, and 2 ns FWHM, respectively. These MC results should be used as a guide to understand the performance limits of the pixelated CdZnTe detector due to the underlying detection processes, with the understanding of the inherent limitations of MC methods.
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http://dx.doi.org/10.1088/0031-9155/57/22/7355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026640PMC
November 2012

NEMA NU 4-2008 comparison of preclinical PET imaging systems.

J Nucl Med 2012 Aug 14;53(8):1300-9. Epub 2012 Jun 14.

Department of Radiology, University of Manitoba, Winnipeg, Canada.

Unlabelled: The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of small-animal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult.

Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: microPET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET.

Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity.

Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand.
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http://dx.doi.org/10.2967/jnumed.111.099382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128012PMC
August 2012

Image reconstruction and system modeling techniques for virtual-pinhole PET insert systems.

Phys Med Biol 2012 May 11;57(9):2517-38. Epub 2012 Apr 11.

Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO 63130, USA.

Virtual-pinhole PET (VP-PET) imaging is a new technology in which one or more high-resolution detector modules are integrated into a conventional PET scanner with lower resolution detectors. It can locally enhance the spatial resolution and contrast recovery near the add-on detectors, and depending on the configuration, may also increase the sensitivity of the system. This novel scanner geometry makes the reconstruction problem more challenging compared to the reconstruction of data from a stand-alone PET scanner, as new techniques are needed to model and account for the non-standard acquisition. In this paper, we present a general framework for fully 3D modeling of an arbitrary VP-PET insert system. The model components are incorporated into a statistical reconstruction algorithm to estimate an image from the multi-resolution data. For validation, we apply the proposed model and reconstruction approach to one of our custom-built VP-PET systems-a half-ring insert device integrated into a clinical PET/CT scanner. Details regarding the most important implementation issues are provided. We show that the proposed data model is consistent with the measured data, and that our approach can lead to reconstructions with improved spatial resolution and lesion detectability.
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http://dx.doi.org/10.1088/0031-9155/57/9/2517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370660PMC
May 2012

Parallel Beam Approximation for Calculation of Detection Efficiency of Crystals in PET Detector Arrays.

IEEE Trans Nucl Sci 2011 Oct;58(5):2148-2154

Radiology Department, Washington University in St. Louis, St. Louis, MO 63130 USA.

In this work we propose a parallel beam approximation for the computation of the detection efficiency of crystals in a PET detector array. In this approximation the detection efficiency of a crystal is estimated using the distance between source and the crystal and the pre-calculated detection cross section of the crystal in a crystal array which is calculated for a uniform parallel beam of gammas. The pre-calculated detection cross sections for a few representative incident angles and gamma energies can be used to create a look-up table to be used in simulation studies or practical implementation of scatter or random correction algorithms. Utilizing the symmetries of the square crystal array, the pre-calculated look-up tables can be relatively small. The detection cross sections can be measured experimentally, calculated analytically or simulated using a Monte Carlo (MC) approach. In this work we used a MC simulation that takes into account the energy windowing, Compton scattering and factors in the "block effect". The parallel beam approximation was validated by a separate MC simulation using point sources located at different positions around a crystal array. Experimentally measured detection efficiencies were compared with Monte Carlo simulated detection efficiencies. Results suggest that the parallel beam approximation provides an efficient and accurate way to compute the crystal detection efficiency, which can be used for estimation of random and scatter coincidences for PET data corrections.
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http://dx.doi.org/10.1109/TNS.2011.2162962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229852PMC
October 2011

A novel phoswich imaging detector for simultaneous beta and coincidence-gamma imaging of plant leaves.

Phys Med Biol 2011 Sep 9;56(17):5583-98. Epub 2011 Aug 9.

Department of Radiology, Washington University in St Louis, MO, USA.

To meet the growing demand for functional imaging technology for use in studying plant biology, we are developing a novel technique that permits simultaneous imaging of escaped positrons and coincidence gammas from annihilation of positrons within an intake leaf. The multi-modality imaging system will include two planar detectors: one is a typical PET detector array and the other is a phoswich imaging detector that detects both beta and gamma. The novel phoswich detector is made of a plastic scintillator, a lutetium oxyorthosilicate (LSO) array, and a position sensitive photomultiplier tube (PS-PMT). The plastic scintillator serves as a beta detector, while the LSO array serves as a gamma detector and light guide that couples scintillation light from the plastic detector to the PMT. In our prototype, the PMT signal was fed into the Siemens QuickSilver electronics to achieve shaping and waveform sampling. Pulse-shape discrimination based on the detectors' decay times (2.1 ns for plastic and 40 ns for LSO) was used to differentiate beta and gamma events using the common PMT signals. Using our prototype phoswich detector, we simultaneously measured a beta image and gamma events (in single mode). The beta image showed a resolution of 1.6 mm full-width-at-half-maximum using F-18 line sources. Because this shows promise for plant-scale imaging, our future plans include development of a fully functional simultaneous beta-and-coincidence-gamma imager with sub-millimeter resolution imaging capability for both modalities.
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http://dx.doi.org/10.1088/0031-9155/56/17/008DOI Listing
September 2011

A sub-millimeter resolution PET detector module using a multi-pixel photon counter array.

Phys Med Biol 2010 May 14;55(9):2573-87. Epub 2010 Apr 14.

Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.

A PET block detector module using an array of sub-millimeter lutetium oxyorthosilicate (LSO) crystals read out by an array of surface-mount, semiconductor photosensors has been developed. The detector consists of a LSO array, a custom acrylic light guide, a 3 x 3 multi-pixel photon counter (MPPC) array (S10362-11-050P, Hamamatsu Photonics, Japan) and a readout board with a charge division resistor network. The LSO array consists of 100 crystals, each measuring 0.8 x 0.8 x 3 mm(3) and arranged in 0.86 mm pitches. A Monte Carlo simulation was used to aid the design and fabrication of a custom light guide to control distribution of scintillation light over the surface of the MPPC array. The output signals of the nine MPPC are multiplexed by a charge division resistor network to generate four position-encoded analog outputs. Flood image, energy resolution and timing resolution measurements were performed using standard NIM electronics. The linearity of the detector response was investigated using gamma-ray sources of different energies. The 10 x 10 array of 0.8 mm LSO crystals was clearly resolved in the flood image. The average energy resolution and standard deviation were 20.0% full-width at half-maximum (FWHM) and +/-5.0%, respectively, at 511 keV. The timing resolution of a single MPPC coupled to a LSO crystal was found to be 857 ps FWHM, and the value for the central region of detector module was 1182 ps FWHM when +/-10% energy window was applied. The nonlinear response of a single MPPC when used to read out a single LSO was observed among the corner crystals of the proposed detector module. However, the central region of the detector module exhibits significantly less nonlinearity (6.5% for 511 keV). These results demonstrate that (1) a charge-sharing resistor network can effectively multiplex MPPC signals and reduce the number of output signals without significantly degrading the performance of a PET detector and (2) a custom light guide to permit light sharing among multiple MPPC and to diffuse and direct scintillation light can reduce the nonlinearity of the detector response within the limited dynamic range of a typical MPPC. As a result, the proposed PET detector module has the potential to be refined for use in high-resolution PET insert applications.
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http://dx.doi.org/10.1088/0031-9155/55/9/010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975434PMC
May 2010

Compton Scattering in Clinical PET/CT With High Resolution Half Ring PET Insert Device.

IEEE Trans Nucl Sci 2010 ;57(3):1045-1051

Radiology Department, Washington University in St. Louis, St. Louis, MO 63130 USA.

The integration of a high resolution PET insert into a conventional PET system can significantly improve the resolution and the contrast of its images within a reduced imaging field of view. For the rest of the scanner imaging field of view, the insert is a highly attenuating and scattering media. In order to use all available coincidence events (including coincidences between 2 detectors in the original scanner, namely the scanner-scanner coincidences), appropriate scatter and attenuation corrections have to be implemented. In this work, we conducted a series of Monte Carlo simulations to estimate the composition of the scattering background and the importance of the scatter correction. We implemented and tested the Single Scatter Simulation (SSS) algorithm for a hypothetical system and show good agreement between the estimated scatter using SSS and Monte Carlo simulated scatter contribution. We further applied the SSS to estimate scatter contribution from an existing prototype PET insert for a clinical PET/CT scanner. The results demonstrated the applicability of SSS to estimate the scatter contribution within a clinical PET/CT system even when there is a high resolution half ring PET insert device in its imaging field of view.
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http://dx.doi.org/10.1109/TNS.2010.2046754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087385PMC
January 2010

Micro insert: a prototype full-ring PET device for improving the image resolution of a small-animal PET scanner.

J Nucl Med 2008 Oct 15;49(10):1668-76. Epub 2008 Sep 15.

Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri, USA.

Unlabelled: A full-ring PET insert device should be able to enhance the image resolution of existing small-animal PET scanners.

Methods: The device consists of 18 high-resolution PET detectors in a cylindric enclosure. Each detector contains a cerium-doped lutetium oxyorthosilicate array (12 x 12 crystals, 0.72 x 1.51 x 3.75 mm each) coupled to a position-sensitive photomultiplier tube via an optical fiber bundle made of 8 x 16 square multiclad fibers. Signals from the insert detectors are connected to the scanner through the electronics of the disabled first ring of detectors, which permits coincidence detection between the 2 systems. Energy resolution of a detector was measured using a (68)Ge point source, and a calibrated (68)Ge point source stepped across the axial field of view (FOV) provided the sensitivity profile of the system. A (22)Na point source imaged at different offsets from the center characterized the in-plane resolution of the insert system. Imaging was then performed with a Derenzo phantom filled with 19.5 MBq of (18)F-fluoride and imaged for 2 h; a 24.3-g mouse injected with 129.5 MBq of (18)F-fluoride and imaged in 5 bed positions at 3.5 h after injection; and a 22.8-g mouse injected with 14.3 MBq of (18)F-FDG and imaged for 2 h with electrocardiogram gating.

Results: The energy resolution of a typical detector module at 511 keV is 19.0% +/- 3.1%. The peak sensitivity of the system is approximately 2.67%. The image resolution of the system ranges from 1.0- to 1.8-mm full width at half maximum near the center of the FOV, depending on the type of coincidence events used for image reconstruction. Derenzo phantom and mouse bone images showed significant improvement in transaxial image resolution using the insert device. Mouse heart images demonstrated the gated imaging capability of the device.

Conclusion: We have built a prototype full-ring insert device for a small-animal PET scanner to provide higher-resolution PET images within a reduced imaging FOV. Development of additional correction techniques are needed to achieve quantitative imaging with such an insert.
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http://dx.doi.org/10.2967/jnumed.107.050070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021981PMC
October 2008

Virtual-pinhole PET.

J Nucl Med 2008 Mar 20;49(3):471-9. Epub 2008 Feb 20.

Department of Radiology, Washington University, St. Louis, Missouri 63110, USA.

Unlabelled: We proposed and tested a novel geometry for PET system design analogous to pinhole SPECT called the virtual-pinhole PET (VP-PET) geometry to determine whether it could provide high-resolution images.

Methods: We analyzed the effects of photon acolinearity and detector sizes on system resolution and extended the empiric formula for reconstructed image resolution of conventional PET proposed earlier to predict the resolutions of VP-PET. To measure the system resolution of VP-PET, we recorded coincidence events as a (22)Na point source was stepped across the coincidence line of response between 2 detectors made from identical arrays of 12 x 12 lutetium oxyorthosilicate crystals (each measuring 1.51 x 1.51 x 10 mm(3)) separated by 565 mm. To measure reconstructed image resolution, we built 4 VP-PET systems using 4 types of detectors (width, 1.51-6.4 mm) and imaged 4 point sources of (64)Cu (half-life = 12.7 h to allow a long acquisition time). Tangential and radial resolutions were measured and averaged for each source and each system. We then imaged a polystyrene plastic phantom representing a 2.5-cm-thick cross-section of isolated breast volume. The phantom was filled with an aqueous solution of (64)Cu (713 kBq/mL) in which the following were imbedded: 4 spheric tumors ranging from 1.8 to 12.6 mm in inner diameter (ID), 6 micropipettes (0.7- or 1.1-mm ID filled with (64)Cu at 5x, 20x, or 50x background), and a 10.0-mm outer-diameter cold lesion.

Results: The shape and measured full width at half maximum of the line spread functions agree well with the predicted values. Measured reconstructed image resolution (2.40-3.24 mm) was +/-6% of the predicted value for 3 of the 4 systems. In one case, the difference was 12.6%, possibly due to underestimation of the block effect from the low-resolution detector. In phantom experiments, all spheric tumors were detected. Small line sources were detected if the activity concentration is at least 20x background.

Conclusion: We have developed and characterized a novel geometry for PET. A PET system following the VP-PET geometry provides high-resolution images for objects near the system's high-resolution detectors. This geometry may lead to the development of special-purpose PET systems or resolution-enhancing insert devices for conventional PET scanners.
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http://dx.doi.org/10.2967/jnumed.107.043034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024474PMC
March 2008

A feasibility study of a prototype PET insert device to convert a general-purpose animal PET scanner to higher resolution.

J Nucl Med 2008 Jan 12;49(1):79-87. Epub 2007 Dec 12.

Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri 63110, USA.

Unlabelled: We developed a prototype system to evaluate the feasibility of using a PET insert device to achieve higher resolution from a general-purpose animal PET scanner.

Methods: The system consists of a high-resolution PET detector, a computer-controlled rotation stage, and a custom mounting plate. The detector consists of a cerium-doped lutetium oxyorthosilicate array (12 x 12 crystals, 0.8 x 1.66 x 3.75 mm(3) each) directly coupled to a position-sensitive photomultiplier tube (PS-PMT). The detector signals were fed into the scanner electronics to establish coincidences between the 2 systems. The detector was mounted to a rotation stage that is attached to the scanner via the custom mounting plate after removing the transmission source holder. The rotation stage was concentric with the center of the scanner. The angular offset of the insert detector was calibrated via optimizing point-source images. In all imaging experiments, coincidence data were collected from 9 angles to provide 180 degrees sampling. A (22)Na point source was imaged at different offsets from the center to characterize the in-plane resolution of the insert system. A (68)Ge point source was stepped across the axial field of view to measure the sensitivity of the system. A 23.2-g mouse was injected with 38.5 MBq of (18)F-fluoride and imaged at 3 h after injection for 2 h.

Results: The transverse image resolution of the PET insert device ranges from 1.1- to 1.4-mm full width at half maximum (FWHM) without correction for the point-source dimension. This corresponds to approximately 33% improvement over the resolution of the original scanner (1.7- to 1.8-mm FWHM) in 2 of the 3 directions. The sensitivity of the device is 0.064% at the center of the field, 46-fold lower than the sensitivity of an existing animal PET scanner. The mouse bone scan had improved image resolution using the PET insert device over that of the existing animal PET scanner alone.

Conclusion: We have demonstrated the feasibility of using a high-resolution insert device in an existing PET scanner to provide high-resolution PET. A PET insert device with more detector modules will improve sensitivity and may become an alternative to special-purpose PET systems for high-resolution PET.
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http://dx.doi.org/10.2967/jnumed.107.044149DOI Listing
January 2008