Trapping of Nicotinic Acetylcholine Receptor Ligands Assayed by In Vitro Cellular Studies and In Vivo PET Imaging.

A question relevant to nicotine addiction is how nicotine and other nicotinic receptor membrane-permeant ligands, such as the anti-smoking drug varenicline (Chantix), distribute in brain. Ligands, like varenicline, with high pKa and high affinity for α4ß2-type nicotinic receptors (α4ß2Rs) are trapped in intracellular acidic vesicles containing α4ß2Rs in vitro Nicotine, with lower pKa and α4ß2R affinity, is not trapped. Here, we extend our results by imaging nicotinic PET ligands in vivo in male and female mouse brain and identifying the trapping brain organelle in vitro as Golgi satellites (GSats). Two PET 18F-labeled imaging ligands were chosen: [18F]2-FA85380 (2-FA) with varenicline-like pKa and affinity and [18F]Nifene with nicotine-like pKa and affinity. [18F]2-FA PET-imaging kinetics were very slow consistent with 2-FA trapping in α4ß2R-containing GSats. In contrast, [18F]Nifene kinetics were rapid, consistent with its binding to α4ß2Rs but no trapping. Specific [18F]2-FA and [18F]Nifene signals were eliminated in ß2 subunit knock-out (KO) mice or by acute nicotine (AN) injections demonstrating binding to sites on ß2-containing receptors. Chloroquine (CQ), which dissipates GSat pH gradients, reduced [18F]2-FA distributions while having little effect on [18F]Nifene distributions in vivo consistent with only [18F]2-FA trapping in GSats. These results are further supported by in vitro findings where dissipation of GSat pH gradients blocks 2-FA trapping in GSats without affecting Nifene. By combining in vitro and in vivo imaging, we mapped both the brain-wide and subcellular distributions of weak-base nicotinic receptor ligands. We conclude that ligands, such as varenicline, are trapped in neurons in α4ß2R-containing GSats, which results in very slow release long after nicotine is gone after smoking.SIGNIFICANCE STATEMENT Mechanisms of nicotine addiction remain poorly understood. An earlier study using in vitro methods found that the anti-smoking nicotinic ligand, varenicline (Chantix) was trapped in α4ß2R-containing acidic vesicles. Using a fluorescent-labeled high-affinity nicotinic ligand, this study provided evidence that these intracellular acidic vesicles were α4ß2R-containing Golgi satellites (GSats). In vivo PET imaging with F-18-labeled nicotinic ligands provided additional evidence that differences in PET ligand trapping in acidic vesicles were the cause of differences in PET ligand kinetics and subcellular distributions. These findings combining in vitro and in vivo imaging revealed new mechanistic insights into the kinetics of weak base PET imaging ligands and the subcellular mechanisms underlying nicotine addiction.

Evaluation of an Image-Derived Input Function for Kinetic Modeling of Nicotinic Acetylcholine Receptor-Binding PET Ligands in Mice.

Positron emission tomography (PET) radioligands that bind with high-affinity to α4ß2-type nicotinic receptors (α4ß2Rs) allow for in vivo investigations of the mechanisms underlying nicotine addiction and smoking cessation. Here, we investigate the use of an image-derived arterial input function and the cerebellum for kinetic analysis of radioligand binding in mice. Two radioligands were explored: 2-[18F]FA85380 (2-FA), displaying similar pKa and binding affinity to the smoking cessation drug varenicline (Chantix), and [18F]Nifene, displaying similar pKa and binding affinity to nicotine. Time-activity curves of the left ventricle of the heart displayed similar distribution across wild type mice, mice lacking the ß2-subunit for ligand binding, and acute nicotine-treated mice, whereas reference tissue binding displayed high variation between groups. Binding potential estimated from a two-tissue compartment model fit of the data with the image-derived input function were higher than estimates from reference tissue-based estimations. Rate constants of radioligand dissociation were very slow for 2-FA and very fast for Nifene. We conclude that using an image-derived input function for kinetic modeling of nicotinic PET ligands provides suitable results compared to reference tissue-based methods and that the chemical properties of 2-FA and Nifene are suitable to study receptor response to nicotine addiction and smoking cessation therapies.

Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics.

In the field of nuclear medicine, the ß+ -emitting 43Sc and ß- -emitting 47Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, scandium is a group-3 transition metal (like 177Lu) and exhibits affinity for DOTA-based chelators, which have been studied in depth, making the barrier to implementation lower for 43/47Sc than for other proposed true theranostics. Before 43/47Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established and each isotope's radiolabeling and animal imaging capabilities studied with a widely utilized tracer. As such, a simple means of converting an 18 MeV biomedical cyclotron to support solid targets and produce 43Sc via the 42Ca(d,n)43Sc reaction has been devised, exhibiting reasonable yields. The NatTi(γ,p)47Sc reaction is also investigated along with the successful implementation of chemical separation and purification methods for 43/47Sc. The conjugation of 43/47Sc with PSMA-617 at specific activities of up to 8.94 MBq/nmol and the subsequent imaging of LNCaP-ENZaR tumor xenografts in mouse models with both 43/47Sc-PSMA-617 are also presented.

The optimal 18F-fluoromisonidazole PET threshold to define tumor hypoxia in preclinical squamous cell carcinomas using pO2 electron paramagnetic resonance imaging as reference truth.

PURPOSE: To identify the optimal threshold in 18F-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pO2 EPRI) as ground truth for hypoxia, defined by pO2 [Formula: see text] 10 mmHg. METHODS: Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue. Dynamic contrast enhanced (DCE) MRI parametric images of Ktrans and ve were generated to model tumor vascular properties. Images from PET/EPR/MRI were co-registered and resampled to isotropic 0.5 mm voxel resolution for analysis. PET images were converted to standardized uptake value (SUV) and tumor-to-muscle ratio (TMR) units. FMISO uptake thresholds were evaluated using receiver operating characteristic (ROC) curve analysis to find the optimal FMISO threshold and unit with maximum overall hypoxia similarity (OHS) with pO2 EPRI, where OHS = 1 shows perfect overlap and OHS = 0 shows no overlap. The means of dice similarity coefficient, normalized Hausdorff distance, and accuracy were used to define the OHS. Monotonic relationships between EPRI/PET/DCE-MRI were evaluated with the Spearman correlation coefficient ([Formula: see text]) to quantify association of vasculature on hypoxia imaged with both FMISO PET and pO2 EPRI. RESULTS: FMISO PET thresholds to define hypoxia with maximum OHS (both OHS = 0.728 [Formula: see text] 0.2) were SUV [Formula: see text] 1.4 [Formula: see text] SUVmean and SUV [Formula: see text] 0.6 [Formula: see text] SUVmax. Weak-to-moderate correlations (|[Formula: see text]|< 0.70) were observed between PET/EPRI hypoxia images with vascular permeability (Ktrans) or fractional extracellular-extravascular space (ve) from DCE-MRI. CONCLUSION: This is the first in vivo comparison of FMISO uptake with pO2 EPRI to identify the optimal FMISO threshold to define tumor hypoxia, which may successfully direct hypoxic tumor boosts in patients, thereby enhancing tumor control.

Simultaneous activity and attenuation estimation in TOF-PET with TV-constrained nonconvex optimization.

An alternating direction method of multipliers (ADMM) framework is developed for nonsmooth biconvex optimization for inverse problems in imaging. In particular, the simultaneous estimation of activity and attenuation (SAA) problem in time-of-flight positron emission tomography (TOF-PET) has such a structure when maximum likelihood estimation (MLE) is employed. The ADMM framework is applied to MLE for SAA in TOF-PET, resulting in the ADMM-SAA algorithm. This algorithm is extended by imposing total variation (TV) constraints on both the activity and attenuation map, resulting in the ADMM-TVSAA algorithm. The performance of this algorithm is illustrated using the penalized maximum likelihood activity and attenuation estimation (P-MLAA) algorithm as a reference. Additional results on step-size tuning and on the use of unconstrained ADMM-SAA are presented in the previous arXiv submission: arXiv:2303.17042v1.

Simultaneous Activity and Attenuation Estimation in TOF-PET With TV-Constrained Nonconvex Optimization.

An alternating direction method of multipliers (ADMM) framework is developed for nonsmooth biconvex optimization for inverse problems in imaging. In particular, the simultaneous estimation of activity and attenuation (SAA) problem in time-of-flight positron emission tomography (TOF-PET) has such a structure when maximum likelihood estimation (MLE) is employed. The ADMM framework is applied to MLE for SAA in TOF-PET, resulting in the ADMM-SAA algorithm. This algorithm is extended by imposing total variation (TV) constraints on both the activity and attenuation map, resulting in the ADMM-TVSAA algorithm. The performance of this algorithm is illustrated using the penalized maximum likelihood activity and attenuation estimation (P-MLAA) algorithm as a reference.

Validation of the design of a high-sensitivity and high-resolution PET system for a preclinical PET/EPR hybrid scanner.

We report the development of a high-sensitivity and high-resolution PET subsystem for a next-generation preclinical PET/EPR hybrid scanner for investigating and improving hypoxia imaging with PET. The PET subsystem consists of 14 detector modules (DM) installed within a cylindrical supporting frame whose outer and inner diameters are 115mm and 60mm, respectively. Each DM contains eight detector units (DU) in a row and each DU is made of a 12×12 array of 1×1×10mm3 LYSO crystals (with a 1.05mm pitch) coupled to a 4×4 silicon photomultiplier (SiPM) array that has a 3.2mm pitch (Hamamatsu multi-pixel photon counter (MPPC) array 14161-3050HS-04). The PET subsystem has a 104mm axial field-of-view (AFOV) that is sufficient for full-body mouse imaging, therefore enabling temporal and spatial correlation studies of tumor hypoxia between PET and EPR. It employs 1mm-width crystals to support sub-millimeter image resolution that is desired for mouse imaging. Al-though a DM contains 1,152 LYSO crystals, by use of a newly devised signal readout method only six outputs are produced. Recently a partial prototype of this subsystem consisting of four DMs is built. In this paper, we present performance measurement results obtained for the developed DMs and initial imaging results obtained by the prototype. The developed DMs show uniformly superior performance in identifying the hit crystal and detector unit, in energy resolution, and in coincidence time resolution. The images obtained for a 22Na point source and a 18F-filled U-shaped tube source show an image resolution of about 1.1mm and 1.2mm FWHM in the transverse and axial directions respectively, and demonstrate successful imaging over the entire 104mm AFOV of the prototype. This estimated image resolution however includes the contribution by the source size.

DOI- and TOF-capable PET array detector using double-ended light readout and stripline-based row and column electronic readout.

We investigate a highly multiplexing readout for depth-of-interaction (DOI) and time-of-flight PET detector consisting of an N×N crystals whose light outputs at the front and back ends are detected by using silicon photomultipliers (SiPM). The front N×N SiPM array is read by using a stripline (SL) configured to support discrimination of the row position of the signal-producing crystal. The back N×N SiPM array is similarly read by an SL for column discrimination. Hence, the detector has only four outputs. We built 4×4 and 8×8 detector modules (DM) by using 3.0×3.0×20 mm3 lutetium-yttrium oxyorthosilicates. The outputs were sampled and processed offline. For both DMs, crystal discrimination was successful. For the 4×4 DM, we obtained an average energy resolution (ER) of 14.1%, an average DOI resolution of 2.5 mm, a non DOI-corrected coincidence resolving time (CRT), measured in coincidence with a single-pixel reference detector, of about 495 ps. For the 8×8 DM, the average ER, average DOI resolution and average CRT were 16.4%, 2.9 mm, and 641 ps, respectively. We identified the intercrystal scattering as a probable cause for the CRT deterioration when the DM was increased from 4×4 to 8×8.

The value of using heterogeneous detector groups for the development of time-of-flight (TOF) positron emission tomography (PET) systems.

Objective. Much recent attention on positron emission tomography (PET) is the development of time-of-flight (TOF) systems with ever-improving coincidence time resolution (CTR). This is because, when all other factors remain the same, a better CTR leads to images of better statistics and effectively increases the sensitivity of the system. However, detector designs that aggressively improve the CTR often compromise the detection efficiency (DE) and offset the benefit gained. Under this circumstance, in developing a TOF PET system it may be beneficial to employ heterogeneous detector groups to balance the overall CTR and DE of the system. In this study, we examine the potential value of this system design strategy by considering two-dimensional systems that assume several representative ways of mixing two detector groups.Approach. The study is based on computer simulation and specifically considers medium time-resolution (MTR) detectors that have a 528 ps CTR and high time-resolution (HTR) detectors that have a 100 ps CTR and a DE that is 0.7 times that of the MTR detector. We examine contrast recovery, noise, and subjective quality of the resulting images under various ways of mixing the MTR and HTR detectors.Main results. With respect to the traditional configuration that adopts only the HTR detectors, symmetric heterogeneous configurations may offer comparable or better images while using considerably fewer HTRs. On the other hand, asymmetric heterogeneous configurations may allow the use of only a few HTRs for improving image quality locally.Significance. This study demonstrates the value of the proposed system-level design strategy of using heterogeneous detector groups for achieving high effective system sensitivity by factoring into the tradeoff between the CTR and DE of the detector.

A Preclinical Positron Emission Tomography (PET) and Electron-Paramagnetic-Resonance-Imaging (EPRI) Hybrid System: PET Detector Module.

We report the design and experimental validation of a compact positron emission tomography (PET) detector module (DM) intended for building a preclinical PET and electron-paramagnetic-resonance-imaging hybrid system that supports sub-millimeter image resolution and high-sensitivity, whole-body animal imaging. The DM is eight detector units (DU) in a row. Each DU contains 12×12 lutetium-yttrium oxyorthosilicate (LYSO) crystals having a 1.05 mm pitch read by 4×4 silicon photomultipliers (SiPM) having a 3.2 mm pitch. A small-footprint, highly-multiplexing readout employing only passive electronics is devised to produce six outputs for the DM, including two outputs derived from SiPM cathodes for determining event time and active DU and four outputs derived from SiPM anodes for determining energy and active crystal. Presently, we have developed two DMs that are 1.28×10.24 cm2 in extent and approximately 1.8 cm in thickness, with their outputs sampled at 0.7 GS/s and analyzed offline. For both DMs, our results show successfully discriminated DUs and crystals. With no correction for SiPM nonlinearity, the average energy resolution for crystals in a DU ranges from 14% to 16%. While not needed for preclinical imaging, the DM may support 300-400 ps time-of-flight resolution.

Multiplexing Readout for Time-of-Flight (TOF) PET Detectors Using Striplines.

A recent trend in PET instrumentation is the use of silicon photomultipliers (SiPMs) for high-resolution and time-of-flight (TOF) detection. Due to its small size, a PET system can use a large number of SiPMs and hence effective and scalable multiplexing readout methods become important. Unfortunately, multiplexing readout generally degrades the fast timing properties necessary for TOF, especially at high channel reduction. Previously, we developed a stripline (SL) based readout method for PET that uses a time-based multiplexing mechanism. This method maintains fast timing by design and has been successfully used for TOF PET detectors. In this paper, we present a more systematic study in which we examine how two important design parameters of the readout - the number of inputs on an SL (n SL) and the pathlength between adjacent input positions (Δℓ) - affect its detection performance properties for PET. Our result shows that, up to n SL = 32 the readout can achieve accurate pixel discrimination and causes little degradation in the energy resolution. The TOF resolution is compromised mildly and a coincidence resolving time on the order of 300 ps FWHM can be achieved for LYSO- and SiPM-based detectors. We also discuss strategies in using the readout to further reduce the number of electronic channels that a PET system would otherwise need.

Improving Tumor Hypoxia Location in 18F-Misonidazole PET with Dynamic Contrast-enhanced MRI Using Quantitative Electron Paramagnetic Resonance Partial Oxygen Pressure Images.

Purpose: To enhance the spatial accuracy of fluorine 18 (18F) misonidazole (MISO) PET imaging of hypoxia by using dynamic contrast-enhanced (DCE) MR images as a basis for modifying PET images and by using electron paramagnetic resonance (EPR) partial oxygen pressure (pO2) as the reference standard. Materials and Methods: Mice (n = 10) with leg-borne MCa4 mammary carcinomas underwent EPR imaging, T2-weighted and DCE MRI, and 18F-MISO PET/CT. Images were registered to the same space for analysis. The thresholds of hypoxia for PET and EPR images were tumor-to-muscle ratios greater than or equal to 2.2 mm Hg and less than or equal to 14 mm Hg, respectively. The Dice similarity coefficient (DSC) and Hausdorff distance (d H ) were used to quantify the three-dimensional overlap of hypoxia between pO2 EPR and 18F-MISO PET images. A training subset (n = 6) was used to calculate optimal DCE MRI weighting coefficients to relate EPR to the PET signal; the group average weights were then applied to all tumors (from six training mice and four test mice). The DSC and d H were calculated before and after DCE MRI-corrected PET images were obtained to quantify the improvement in overlap with EPR pO2 images for measuring tumor hypoxia. Results: The means and standard deviations of the DSC and d H between hypoxic regions in original PET and EPR images were 0.35 mm ± 0.23 and 5.70 mm ± 1.7, respectively, for images of all 10 mice. After implementing a preliminary DCE MRI correction to PET data, the DSC increased to 0.86 mm ± 0.18 and the d H decreased to 2.29 mm ± 0.70, showing significant improvement (P < .001) for images of all 10 mice. Specifically, for images of the four independent test mice, the DSC improved with correction from 0.19 ± 0.28 to 0.80 ± 0.29 (P = .02), and the d H improved from 6.40 mm ± 2.5 to 1.95 mm ± 0.63 (P = .01). Conclusion: Using EPR information as a reference standard, DCE MRI information can be used to correct 18F-MISO PET information to more accurately reflect areas of hypoxia.Keywords: Animal Studies, Molecular Imaging, Molecular Imaging-Cancer, PET/CT, MR-Dynamic Contrast Enhanced, MR-Imaging, PET/MR, Breast, Oncology, Tumor Mircoenvironment, Electron Paramagnetic ResonanceSupplemental material is available for this article.© RSNA, 2021.

Potentials of Digitally Sampling Scintillation Pulses in Timing Determination in PET.

We investigate the potentials of digitally sampling scintillation pulses techniques for positron emission tomography (PET) in this paper, focusing on the determination of the event time. We have built, and continue building, a digital library of PET event waveforms generated with various combinations of photo-detectors and scintillator materials, with various crystal sizes. Events in this digital library are obtained at a high sampling of 20 GSps (Giga-samples per second) so that their waveforms are recorded with high accuracy. To explore the potential advantages of digitally sampling scintillation pulses, we employ a dataset in the above-mentioned library to evaluate two methods for digitizing the event pulses and linear interpolation techniques to analyze the resulting digital samples. Our results show that the two digitization methods that we studied can yield a coincidence timing resolution of about 300 ps FWHM when applied to events generated by a pair of LSO + PMT detector units. This timing resolution is comparable with that is achieved by the same detector pair with a constant fraction discriminator (CFD). As a benchmark, regular-time sampling (RTS) method, usually implemented with very fast traditional analog-to-digital converters (ADCs) for digitizing scintillation pulses, is not feasible for a multi-channel system like a PET system. Digitizing scintillation pulses with multi-voltage threshold (MVT) method could be implemented at a reasonable cost for a PET system. With digitized PET event samples, various digital signal processing (DSP) techniques can be implemented to determine event arrival time. Our results have therefore demonstrated the promising potentials of digitally sampling scintillation pulses techniques in PET imaging.

Windowed image reconstruction for time-of-flight positron emission tomography.

It has been well recognized that, in comparison with the conventional positron emission tomography (PET), the differential-time measurements made available in time-of-flight (TOF) PET imaging can reduce the propagation of data noise in reconstruction and lead to images having better statistical quality. This observation has been the motivation driving the interest in developing TOF-PET systems. In this paper, we make new observations that can extend the use of TOF-PET. We develop a new mathematical formulation showing that the TOF information can be utilized to achieve new modes of reconstruction. In particular, it enables windowed and regions-of-interest reconstructions by use of TOF-PET measurements having a restricted coverage in the TOF or transverse direction, or both. A class of analytic algorithms is developed to perform such reconstructions. We employ computer-simulated TOF-PET data containing Poisson noise to validate the developed algorithms and evaluate their response to data noise with respect to a confidence-weighting analytic TOF-PET reconstruction method. We also demonstrate that in certain situations, the new reconstruction algorithms can generate images having improved statistics by recruiting suitable subsets of the TOF-PET data to minimize the use of deteriorating measurements in reconstruction. Potential implications of the new reconstruction approach to PET imaging are discussed.

Optimization-Based Image Reconstruction From Low-Count, List-Mode TOF-PET Data.

OBJECTIVE: We investigate an optimization-based approach to image reconstruction from list-mode data in digital time-of-flight (TOF) positron emission tomography (PET) imaging. METHOD: In the study, the image to be reconstructed is designed as a solution to a convex, non-smooth optimization program, and a primal-dual algorithm is developed for image reconstruction by solving the optimization program. The algorithm is first applied to list-mode TOF-PET data of a typical count level from physical phantoms and a human subject. Subsequently, we explore the algorithm's potential for image reconstruction in low-dose and/or fast TOF-PET imaging of practical interest by applying the algorithm to list-mode TOF-PET data of different, low-count levels from the same physical phantoms and human subject. RESULTS: Visual inspection and quantitative-metric analysis reveal that the optimization reconstruction approach investigated can yield images with enhanced spatial and contrast resolution, suppressed image noise, and increased axial volume coverage over the reference images obtained with a standard clinical reconstruction algorithm especially for low-dose TOF-PET data. SIGNIFICANCE: The optimization-based reconstruction approach can be exploited for yielding insights into potential quality upper bound of reconstructed images in, and design of scanning protocols of, TOF-PET imaging of practical significance.

Rational design of silicon structures for optically controlled multiscale biointerfaces.

Silicon-based materials have been widely used. However, remotely controlled and interconnect-free silicon configurations have been rarely explored, because of limited fundamental understanding of the complex physicochemical processes that occur at interfaces between silicon and biological materials. Here, we describe rational design principles, guided by biology, for establishing intracellular, intercellular and extracellular silicon-based interfaces, where the silicon and the biological targets have matched properties. We focused on light-induced processes at these interfaces, and developed a set of matrices to quantify and differentiate the capacitive, Faradaic and thermal outputs from about 30 different silicon materials in saline. We show that these interfaces are useful for the light-controlled non-genetic modulation of intracellular calcium dynamics, of cytoskeletal structures and transport, of cellular excitability, of neurotransmitter release from brain slices, and of brain activity in vivo.

Modularized compact positron emission tomography detector for rapid system development.

We report the development of a modularized compact positron emission tomography (PET) detector that outputs serial streams of digital samples of PET event pulses via an Ethernet interface using the UDP/IP protocol to enable rapid configuration of a PET system by connecting multiple such detectors via a network switch to a computer. Presently, the detector is [Formula: see text] in extent (excluding I/O connectors) and contains an [Formula: see text] array of [Formula: see text] one-to-one coupled lutetium-yttrium oxyorthosilicate/silicon photomultiplier pixels. It employs cross-wire and stripline readouts to merge the outputs of the 216 detector pixels to 24 channels. Signals at these channels are sampled using a built-in 24-ch, 4-level field programmable gate arrays-only multivoltage threshold digitizer. In the computer, software programs are implemented to analyze the digital samples to extract event information and to perform energy qualification and coincidence filtering. We have developed two such detectors. We show that all their pixels can be accurately discriminated and measure a crystal-level energy resolution of 14.4% to 19.4% and a detector-level coincidence time resolution of 1.67 ns FWHM. Preliminary imaging results suggests that a PET system based on the detectors can achieve an image resolution of [Formula: see text].

Investigation of optimization-based reconstruction with an image-total-variation constraint in PET.

Interest remains in reconstruction-algorithm research and development for possible improvement of image quality in current PET imaging and for enabling innovative PET systems to enhance existing, and facilitate new, preclinical and clinical applications. Optimization-based image reconstruction has been demonstrated in recent years of potential utility for CT imaging applications. In this work, we investigate tailoring the optimization-based techniques to image reconstruction for PET systems with standard and non-standard scan configurations. Specifically, given an image-total-variation (TV) constraint, we investigated how the selection of different data divergences and associated parameters impacts the optimization-based reconstruction of PET images. The reconstruction robustness was explored also with respect to different data conditions and activity up-takes of practical relevance. A study was conducted particularly for image reconstruction from data collected by use of a PET configuration with sparsely populated detectors. Overall, the study demonstrates the robustness of the TV-constrained, optimization-based reconstruction for considerably different data conditions in PET imaging, as well as its potential to enable PET configurations with reduced numbers of detectors. Insights gained in the study may be exploited for developing algorithms for PET-image reconstruction and for enabling PET-configuration design of practical usefulness in preclinical and clinical applications.

Spatial-resolution enhancement in computed tomography.

We propose an approach that combines an asymmetric fan-beam configuration and a new reconstruction algorithm to enhancing spatial resolution in computed tomography (CT). The asymmetric configuration can be achieved by changing the center of rotation (COR) from the conventional symmetric configuration. It does not, however, require new detectors and X-ray source nor alter the relative geometry between the detector and the X-ray source. By effectively reducing the distance of the COR to the X-ray source, the asymmetric configuration can increase the effective sampling density in projection data without reducing the size of the field of view (FOV). The proposed algorithm, on the other hand, can reconstruct images directly from data acquired with this asymmetric configuration. We performed numerical studies to demonstrate and validate the proposed acquisition/reconstruction approach. Results in these studies confirm that the proposed approach can lead to enhanced spatial resolution in reconstructed images. The proposed acquisition/reconstruction approach may find applications in micro-CT and industrial CT in which the CORs may be changed.

Performance evaluation of the Trans-PET® BioCaliburn® LH system: a large FOV small-animal PET system.

UNLABELLED: The Trans-PET(®) BioCaliburn(®) LH is a commercial positron emission tomography (PET) system for animal imaging. The system offers a large transaxial field-of-view (FOV) of 13.0 cm to allow imaging of multiple rodents or larger animals. This paper evaluates and reports the performance characteristics of this system. METHODS: in this paper, the system was evaluated for its spatial resolutions, sensitivity, scatter fraction, count rate performance and image quality in accordance with the National Electrical Manufacturers Association (NEMA) NU-4 2008 specification with modifications. Phantoms and animals not specified in the NEMA specification were also scanned to provide further demonstration of its imaging capability. RESULTS: the spatial resolution is 1.0 mm at the center. When using a 350-650 keV energy window and a 5 ns coincidence time window, the sensitivity at the center is 2.04%. The noise equivalent count-rate curve reaches a peak value of 62 kcps at 28 MBq for the mouse-sized phantom and a peak value of 25 kcps at 31 MBq for the rat-sized phantom. The scatter fractions are 8.4% and 17.7% for the mouse- and rat-sized phantoms, respectively. The uniformity and recovery coefficients measured by using the NEMA image-quality phantom both indicate good imaging performance, even though the reconstruction algorithm provided by the vendor does not implement all desired corrections. The Derenzo-phantom images show that the system can resolve 1.0 mm diameter rods. Animal studies demonstrate the capabilities of the system in dynamic imaging and to image multiple rodents. CONCLUSION: the Trans-PET(®) BioCaliburn(®) LH system offers high spatial resolution, a large transaixal FOV and adequate sensitivity. It produces animal images of good quality and supports dynamic imaging. The system is an attractive imaging technology for preclinical research.