Yttrium-90 Activity Quantification in PET/CT-Guided Biopsy Specimens from Colorectal Hepatic Metastases Immediately after Transarterial Radioembolization Using Micro-CT and Autoradiography.

PURPOSE: To evaluate the yttrium-90 (90Y) activity distribution in biopsy tissue samples of the treated liver to quantify the dose with higher spatial resolution than positron emission tomography (PET) for accurate investigation of correlations with microscopic biological effects and to evaluate the radiation safety of this procedure. MATERIALS AND METHODS: Eighty-six core biopsy specimens were obtained from 18 colorectal liver metastases (CLMs) immediately after 90Y transarterial radioembolization (TARE) with either resin or glass microspheres using real-time 90Y PET/CT guidance in 17 patients. A high-resolution micro-computed tomography (micro-CT) scanner was used to image the microspheres in part of the specimens and allow quantification of 90Y activity directly or by calibrating autoradiography (ARG) images. The mean doses to the specimens were derived from the measured specimens' activity concentrations and from the PET/CT scan at the location of the biopsy needle tip for all cases. Staff exposures were monitored. RESULTS: The mean measured 90Y activity concentration in the CLM specimens at time of infusion was 2.4 ± 4.0 MBq/mL. The biopsies revealed higher activity heterogeneity than PET. Radiation exposure to the interventional radiologists during post-TARE biopsy procedures was minimal. CONCLUSIONS: Counting the microspheres and measuring the activity in biopsy specimens obtained after TARE are safe and feasible and can be used to determine the administered activity and its distribution in the treated and biopsied liver tissue with high spatial resolution. Complementing 90Y PET/CT imaging with this approach promises to yield more accurate direct correlation of histopathological changes and absorbed dose in the examined specimens.

High-Resolution Anamorphic SPECT Imaging.

We have developed a gamma-ray imaging system that combines a high-resolution silicon detector with two sets of movable, half-keel-edged copper-tungsten blades configured as crossed slits. These apertures can be positioned independently between the object and detector, producing an anamorphic image in which the axial and transaxial magnifications are not constrained to be equal. The detector is a 60 mm × 60 mm, one-millimeter-thick, one-megapixel silicon double-sided strip detector with a strip pitch of 59 µm. The flexible nature of this system allows the application of adaptive imaging techniques. We present system details; calibration, acquisition, and reconstruction methods; and imaging results.

Fisher Information Analysis of Depth-of-Interaction Estimation in Double-Sided Strip Detectors.

In very-high-spatial-resolution gamma-ray imaging applications, such as preclinical PET and SPECT, estimation of 3D interaction location inside the detector crystal can be used to minimize parallax error in the imaging system. In this work, we investigate the effect of bias voltage setting on depth-of-interaction (DOI) estimates for a semiconductor detector with a double-sided strip geometry. We first examine the statistical properties of the signals and develop expressions for likelihoods for given gamma-ray interaction positions. We use Fisher Information to quantify how well (in terms of variance) the measured signals can be used for DOI estimation with different bias-voltage settings. We performed measurements of detector response versus 3D position as a function of applied bias voltage by scanning with highly collimated synchrotron radiation at the Advanced Photon Source at Argonne National Laboratory. Experimental and theoretical results show that the optimum bias setting depends on whether or not the estimated event position will include the depth of interaction. We also found that for this detector geometry, the z-resolution changes with depth.

Correction of multiplexing artefacts in multi-pinhole SPECT through temporal shuttering, de-multiplexing of projections, and alternating reconstruction.

Objective.Single-photon emission computed tomography (SPECT) with pinhole collimators can provide high-resolution imaging, but is often limited by low sensitivity. Acquiring projections simultaneously through multiple pinholes affords both high resolution and high sensitivity. However, the overlap of projections from different pinholes on detectors, known as multiplexing, has been shown to cause artefacts which degrade reconstructed images.Approach.Multiplexed projection sets were considered here using an analytic simulation model of AdaptiSPECT-C-a brain-dedicated multi-pinhole SPECT system. AdaptiSPECT-C has fully adaptable aperture shutters, so can acquire projections with a combination of multiplexed and non-multiplexed frames using temporal shuttering. Two strategies for reducing multiplex artefacts were considered: an algorithm to de-multiplex projections, and an alternating reconstruction strategy for projections acquired with a combination of multiplexed and non-multiplexed frames. Geometric and anthropomorphic digital phantoms were used to assess a number of metrics.Main results.Both de-multiplexing strategies showed a significant reduction in image artefacts and improved fidelity, image uniformity, contrast recovery and activity recovery (AR). In all cases, the two de-multiplexing strategies resulted in superior metrics to those from images acquired with only mux-free frames. The de-multiplexing algorithm provided reduced image noise and superior uniformity, whereas the alternating strategy improved contrast and AR.Significance.The use of these de-multiplexing algorithms means that multi-pinhole SPECT systems can acquire projections with more multiplexing without degradation of images.

Characterization, Bioactivity, and Biodistribution of 35 kDa Hyaluronan Fragment.

It has been reported that hyaluronic acid (HA) with a 35 kDa molecular weight (HA35) acts biologically to protect tissue from injury, but its biological properties are not yet fully characterized. This study aimed to evaluate the cellular effects and biodistribution of HA35 compared to HA with a 1600 kDa molecular weight (HA1600). We assessed the effects of HA35 and HA1600 on cell migration, NO and ROS generation, and gene expression in cultured macrophages, microglia, and lymphocytes. HA35 was separately radiolabeled with 99mTc and 125I and administered to C57BL/6J mice for in vivo biodistribution imaging. In vitro studies indicated that HA35 and HA1600 similarly enhanced cell migration through HA receptor binding mechanisms, reduced the generation of NO and ROS, and upregulated gene expression profiles related to cell signaling pathways in immune cells. HA35 showed a more pronounced effect in regulating a broader range of genes in macrophages and microglia than HA1600. Upon intradermal or intravenous administration, radiolabeled HA35 rapidly accumulated in the liver, spleen, and lymph nodes. In conclusion, HA35 not only exhibits effects on cellular bioactivity comparable to those of HA1600 but also exerts biological effects on a broader range of immune cell gene expression. The findings herein offer valuable insights for further research into the therapeutic potential of HA35 in inflammation-mediated tissue injury.

An eNAMPT-neutralizing mAb reduces post-infarct myocardial fibrosis and left ventricular dysfunction.

Myocardial infarction (MI) triggers adverse ventricular remodeling (VR), cardiac fibrosis, and subsequent heart failure. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is postulated to play a significant role in VR processing via activation of the TLR4 inflammatory pathway. We hypothesized that an eNAMPT specific monoclonal antibody (mAb) could target and neutralize overexpressed eNAMPT post-MI and attenuate chronic cardiac inflammation and fibrosis. We investigated humanized ALT-100 and ALT-300 mAb with high eNAMPT-neutralizing capacity in an infarct rat model to test our hypothesis. ALT-300 was 99mTc-labeled to generate 99mTc-ALT-300 for imaging myocardial eNAMPT expression at 2 hours, 1 week, and 4 weeks post-IRI. The eNAMPT-neutralizing ALT-100 mAb (0.4 mg/kg) or saline was administered intraperitoneally at 1 hour and 24 hours post-reperfusion and twice a week for 4 weeks. Cardiac function changes were determined by echocardiography at 3 days and 4 weeks post-IRI. 99mTc-ALT-300 uptake was initially localized to the ischemic area at risk (IAR) of the left ventricle (LV) and subsequently extended to adjacent non-ischemic areas 2 hours to 4 weeks post-IRI. Radioactive uptake (%ID/g) of 99mTc-ALT-300 in the IAR increased from 1 week to 4 weeks (0.54 ± 0.16 vs. 0.78 ± 0.13, P < 0.01). Rats receiving ALT-100 mAb exhibited significantly improved myocardial histopathology and cardiac function at 4 weeks, with a significant reduction in the collagen volume fraction (%LV) compared to controls (21.5 ± 6.1% vs. 29.5 ± 9.9%, P < 0.05). Neutralization of the eNAMPT/TLR4 inflammatory cascade is a promising therapeutic strategy for MI by reducing chronic inflammation, fibrosis, and preserving cardiac function.

Resolution recovery on list mode MLEM reconstruction for dynamic cardiac SPECT system.

The Dynamic Cardiac SPECT (DC-SPECT) system is being developed at the Massachusetts General Hospital, featuring a static cardio focus asymmetrical geometry enabling simultaneous high-resolution and high-sensitivity imaging. Among 14 design iterations of the DC-SPECT with varying number of detector heads, system sensitivity and resolution, the current version under development features 10 mm FWHM geometrical resolution (without resolution recovery) and 0.07% sensitivity at the center of the FOV, this is 1.5× resolution gain and 7× sensitivity gain compared to a conventional dual head gamma camera (0.01% sensitivity and 15-mm resolution). This work presents improvement in imaging resolution by implementing a spatially variant point spread function (SV-PSF) with list mode MLEM reconstruction. A resolution recovery method by PSF deconvolution is validated on list mode MLEM reconstruction for the DC-SPECT. A spatial invariant PSF is included as an additional test to show the influence of the PSF modelling accuracy on reconstructed image quality. We compare the MLEM reconstruction with and without PSF deconvolution; an analytic model is used for the calculation of system response, and the results are compared to the reconstruction with system modelling using Monte Carlo (MC) based methods. Results show that with PSF modelling applied, the quality of the reconstructed image is improved, and the DC-SPECT system can achieve a 4.5 mm central spatial resolution with average 795 counts/Mbq. Both the SV-PSF and the spatial-invariant PSF improve the image quality, and the reconstruction with SV-PSF generates line profiles closer to the ground truth. The results show substantial improvement over the GE Discovery 570c performance (7 mm spatial resolution with an average 460 counts/MBq, 5.8 mm resolution at the FOV center). The impact of PSF deconvolution is significant, improvement of the reconstructed image quality is evident in comparison to MC simulated system matrix with the same sampling size in the simulation.

Mesh modeling of system geometry and anatomy phantoms for realistic GATE simulations and their inclusion in SPECT reconstruction.

Objective.Monte-Carlo simulation studies have been essential for advancing various developments in single photon emission computed tomography (SPECT) imaging, such as system design and accurate image reconstruction. Among the simulation software available, Geant4 application for tomographic emission (GATE) is one of the most used simulation toolkits in nuclear medicine, which allows building systems and attenuation phantom geometries based on the combination of idealized volumes. However, these idealized volumes are inadequate for modeling free-form shape components of such geometries. Recent GATE versions alleviate these major limitations by allowing users to import triangulated surface meshes.Approach.In this study, we describe our mesh-based simulations of a next-generation multi-pinhole SPECT system dedicated to clinical brain imaging, called AdaptiSPECT-C. To simulate realistic imaging data, we incorporated in our simulation the XCAT phantom, which provides an advanced anatomical description of the human body. An additional challenge with the AdaptiSPECT-C geometry is that the default voxelized XCAT attenuation phantom was not usable in our simulation due to intersection of objects of dissimilar materials caused by overlap of the air containing regions of the XCAT beyond the surface of the phantom and the components of the imaging system.Main results.We validated our mesh-based modeling against the one constructed by idealized volumes for a simplified single vertex configuration of AdaptiSPECT-C through simulated projection data of123I-activity distributions. We resolved the overlap conflict by creating and incorporating a mesh-based attenuation phantom following a volume hierarchy. We then evaluated our reconstructions with attenuation and scatter correction for projections obtained from simulation consisting of mesh-based modeling of the system and the attenuation phantom for brain imaging. Our approach demonstrated similar performance as the reference scheme simulated in air for uniform and clinical-like123I-IMP brain perfusion source distributions.Significance.This work enables the simulation of complex SPECT acquisitions and reconstructions for emulating realistic imaging data close to those of actual patients.

PEGylated and Non-PEGylated TCP-1 Probes for Imaging of Colorectal Cancer.

PURPOSE: Previous studies indicate that 99mTc- and fluorescent-labeled c[Cys-Thr-Pro-Ser-Pro-Phe-Ser-His-Cys]OH (TCP-1) peptides were able to detect colorectal cancer (CRC) and tumor-associated vasculature. This study was designed to characterize the targeting properties of PEGylated and non-PEGylated TCP-1 peptides for CRC imaging. PROCEDURES: Cell uptake of cyanine 7 (Cy7)-labeled TCP-1 probes (Cy7-PEG4-TCP-1 and Cy7-TCP-1) was investigated in three CRC cell lines (human, HCT116 and HT29; mouse, CT26). Xenograft and orthotopic CRC tumor models with HCT116 and CT26 cells were used to characterize biodistribution and CRC tumor-targeting properties of TCP-1 fluorescence and radioligand with and without PEGylation, [99mTc]Tc-HYNIC-PEG4-TCP-1 vs. [99mTc]Tc-HYNIC-TCP-1. RESULTS: Fluorescence images showed that TCP-1 probes were distributed in the cytoplasm and nucleus of CRC cells. When CT26 cells were treated with unlabeled TCP-1 peptide prior to the cell incubation with Cy7-PEG4-TCP-1, cell fluorescent signals were significantly reduced relative to the cells without blockade. Relative to Cy7-TCP-1, superior brilliance and visibility of fluorescence was observed in the tumor with Cy7-PEG4-TCP-1 and maintained up to 18 h post-injection. [99mTc]Tc-HYNIC-PEG4-TCP-1 images in xenograft and orthotopic CRC models demonstrated that TCP-1 PEGylation preserved tumor-targeting capability of TCP-1, but its distribution (%ID/g) in the liver and intestine was higher than that of [99mTc]Tc-HYNIC-TCP-1 (1.51 ± 0.29 vs 0.53 ± 0.12, P < 0.01). Better tumor visualization by [99mTc]Tc-HYNIC-TCP-1 was observed in the orthotopic CRC model due to lower intestinal radioactivity. CONCLUSIONS: TCP-1-based probes undergo endocytosis and localize in the cytoplasm and nucleus of human and mouse CRC cells. Tumor detectability of fluorescent TCP-1 peptide with a PEG4 spacer is promising due to its enhanced tumor binding affinity and rapid clearance kinetics from nontumor tissues. Non-PEGylated [99mTc]Tc-HYNIC-TCP-1 exhibits lower nonspecific accumulation in the liver and gastrointestinal tract and might have better capability for detecting CRC lesions in clinical sites. TCP-1 may represent an innovative targeting molecule for detecting CRC noninvasively.

A System Calibration and Fast Iterative Reconstruction Method for Next-Generation SPECT Imagers.

Recently, high-resolution gamma cameras have been developed with detectors containing > 105-106 elements. Single-photon emission computed tomography (SPECT) imagers based on these detectors usually also have a large number of voxel bins and therefore face memory storage issues for the system matrix when performing fast tomographic reconstructions using iterative algorithms. To address these issues, we have developed a method that parameterizes the detector response to a point source and generates the system matrix on the fly during MLEM or OSEM on graphics hardware. The calibration method, interpolation of coefficient data, and reconstruction results are presented in the context of a recently commissioned small-animal SPECT imager, called FastSPECT III.

Use of radiolabeled hyaluronic acid for preclinical assessment of inflammatory injury and acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is accompanied by a dramatic increase in lung hyaluronic acid (HA), leading to a dose-dependent reduction of pulmonary oxygenation. This pattern is associated with severe infections, such as COVID-19, and other important lung injury etiologies. HA actively participates in molecular pathways involved in the cytokine storm of COVID-19-induced ARDS. The objective of this study was to evaluate an imaging approach of radiolabeled HA for assessment of dysregulated HA deposition in mouse models with skin inflammation and lipopolysaccharide (LPS)-induced ARDS using a novel portable intensified Quantum Imaging Detector (iQID) gamma camera system. METHODS: HA of 10 kDa molecular weight (HA10) was radiolabeled with 125I and 99mTc respectively to produce [125I]I-HA10 and [99mTc]Tc-HA10, followed by comparative studies on stability, in vivo biodistribution, and uptake at inflammatory skin sites in mice with 12-O-tetradecanoylphorbol-13-acetate (TPA)-inflamed ears. [99mTc]Tc-HA10 was used for iQID in vivo dynamic imaging of mice with ARDS induced by intratracheal instillation of LPS. RESULTS: [99mTc]Tc-HA10 and [125I]I-HA10 had similar biodistribution and localization at inflammatory sites. [99mTc]Tc-HA10 was shown to be feasible in measuring skin injury and monitoring skin wound healing. [99mTc]Tc-HA10 dynamic pulmonary images yielded good visualization of radioactive uptake in the lungs. There was significantly increased lung uptake and slower lung washout in mice with LPS-induced ARDS than in control mice. Postmortem biodistribution measurement of [99mTc]TcHA10 (%ID/g) was 11.0 ± 3.9 vs. 1.3 ± 0.3 in the ARDS mice (n = 6) and controls (n = 6) (P < 0.001), consistent with upregulated HA expression as determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) staining. CONCLUSIONS: [99mTc]Tc-HA10 is promising as a biomarker for evaluating HA dysregulation that contributes to pulmonary injury in ARDS. Rapid iQID imaging of [99mTc]Tc-HA10 clearance from injured lungs may provide a functional template for timely assessment and quantitative monitoring of pulmonary pathophysiology and intervention in ARDS.

Cerebral SPECT imaging with different acquisition schemes using varying levels of multiplexing versus sensitivity in an adaptive multi-pinhole brain-dedicated scanner.

Application of multi-pinhole collimator in pinhole-based SPECT increases detection sensitivity. The presence of multiplexing in projection images due to the usage of multiple pinholes can further improve the sensitivity at the cost of adding data ambiguity. We are developing a next-generation adaptive brain-dedicated SPECT system -AdaptiSPECT-C. The AdaptiSPECT-C can adapt the multiplexing level and system sensitivity using adaptable pinhole modules. In this study, we investigated the performance of 4 data acquisition schemes with different multiplexing levels and sensitivities on cerebral SPECT imaging. Schemes #1, #2, and #3 have <1%, 67%, and 31% overall multiplexing, respectively, while the 4th scheme without multiplexing is considered as ground truth. The ground-truth and schemes #1-3 have 1.0, 1.7, 5.1, and 4.0 times higher sensitivity, respectively, compared to a dual-headed parallel-hole SPECT system at matched spatial resolution. A customized XCAT brain perfusion digital phantom emulating the distribution of I-123 N-isopropyl iodoamphetamine (IMP) in a 99th percentile size male was used for simulations. Data acquisition for each scheme was performed at two count levels (low-count and high-count relative to the recommended clinical count level). The normalized root-mean-square error (NRMSE) for schemes #1, #2, and #3 with the low-count (high-count) scenario showed 11%, 4%, and 5% (10%, 5%, and 6%) deviation, respectively, from that of the multiplex-free ground truth. For both the low-count and high-count scenarios, scheme #1 resulted in the least accurate activity ratio (AR) for almost all the analyzed gray-matter brain regions. Further schemes #2 or #3 led to the most accurate AR values with both low-count and high-count scenarios for all the analyzed gray-matter regions. It was thus observed that even with this large head size which leads to significant multiplexing levels, the higher sensitivity from multiplexing could to some extent mitigate the data ambiguity and be translated into reconstructed images of higher quality.

Improved Performance of a Multipinhole SPECT for DAT Imaging by Increasing Number of Pinholes at the Expense of Increased Multiplexing.

SPECT imaging of dopamine transporters (DAT) in the brain is a widely utilized study to improve the diagnosis of Parkinsonian syndromes, where conventional (parallel-hole and fan-beam) collimators on dual-head scanners are commonly employed. We have designed a multi-pinhole (MPH) collimator to improve the performance of DAT imaging. The MPH collimator focuses on the striatum and hence offers a better trade-off for sensitivity and spatial resolution than the conventional collimators within this clinically most relevant region for DAT imaging. Our original MPH design consisted of 9 pinholes with a background-to-striatal (Bkg/Str) projection multiplexing of 1% only. In this simulation study, we investigated whether further improvements in the performance of MPH imaging could be obtained by increasing the number of pinholes, hence by enhancing the sensitivity and sampling, despite the ambiguity in reconstructing images due to increased multiplexing. We performed analytic simulations of the MPH configurations with 9, 13, and 16 pinholes (aperture diameters: 4-6mm) using a digital phantom modeling DAT imaging. Our quantitative analyses indicated that using 13 (Bkg/Str: 12%) and 16 (Bkg/Str: 22%) pinholes provided better performance than the original 9-pinhole configuration for the acquisition with 2 or 4 angular views, but a similar performance with 8 and 16 views.

Improvement in sampling and modulation of multiplexing with temporal shuttering of adaptable apertures in a brain-dedicated multi-pinhole SPECT system.

We are developing a multi-detector pinhole-based stationary brain-dedicated SPECT system: AdaptiSPECT-C. In this work, we introduced a new design prototype with multiple adaptable pinhole apertures for each detector to modulate the multiplexing by employing temporal shuttering of apertures. Temporal shuttering of apertures over the scan time provides the AdaptiSPECT-C with the capability of multiple-frame acquisition. We investigated, through analytic simulation, the impact of projection multiplexing on image quality using several digital phantoms and a customized anthropomorphic phantom emulating brain perfusion clinical distribution. The 105 pinholes in the collimator of the system were categorized into central, axial, and lateral apertures. We generated, through simulation, collimators of different multiplexing levels. Several data acquisition schemes were also created by changing the imaging time share of the acquisition frames. Sensitivity increased by 35% compared to the single-pinhole-per-detector base configuration of the AdaptiSPECT-C when using the central, axial, and lateral apertures with equal acquisition time shares within a triple-frame scheme with a high multiplexing scenario. Axial and angular sampling of the base configuration was enhanced by adding the axial and lateral apertures. We showed that the temporal shuttering of apertures can be exploited, trading the sensitivity, to modulate the multiplexing and to acquire a set of non-multiplexed non-truncated projections. Our results suggested that reconstruction benefited from utilizing both non-multiplexed projections and projections with modulated multiplexing resulting in a noticeably reduction in the multiplexing-induced image artefacts. Contrast recovery factor improved by 20% (9%) compared to the base configuration for a Defrise (hot-rod) phantom study when the central and axial (lateral) apertures with equal time shares were combined. The results revealed that, as an overall trend at each simulated multiplexing level, lowest normalized root-mean-square errors for the brain gray-matter regions were achieved with the combined usage of the central apertures and axial/lateral apertures.

Inclusion of quasi-vertex views in a brain-dedicated multi-pinhole SPECT system for improved imaging performance.

With brain-dedicated multi-detector systems employing pinhole apertures the usage of detectors facing the top of the patient's head (i.e. quasi-vertex (QV) views) can provide the advantage of additional viewing from close to the brain for improved detector coverage. In this paper, we report the results of simulation and reconstruction studies to investigate the impact of the QV views on the imaging performance of AdaptiSPECT-C, a brain-dedicated stationary SPECT system under development. In this design, both primary and scatter photons from regions located inferior to the brain can contribute to SPECT projections acquired by the QV views, and thus degrade AdaptiSPECT-C imaging performance. In this work, we determined the proportion, origin, and nature (i.e. primary, scatter, and multiple-scatter) of counts emitted from structures within the head and throughout the body contributing to projections from the different AdaptiSPECT-C detector rings, as well as from a true vertex view detector. We simulated phantoms used to assess different aspects of image quality (i.e. uniform activity concentration sphere, and Derenzo), as well as anthropomorphic phantoms with different count levels emulating clinical 123I activity distributions (i.e. DaTscan and perfusion). We determined that attenuation and scatter in the patient's body greatly diminish the probability of the photons emitted outside the volume of interest reaching to detectors and being recorded within the 15% photopeak energy window. In addition, we demonstrated that the inclusion of the residual of such counts in the system acquisition does not degrade visual interpretation or quantitative analysis. The addition of the QV detectors improves volumetric sensitivity, angular sampling, and spatial resolution leading to significant enhancement in image quality, especially in the striato-thalamic and superior regions of the brain. Besides, the use of QV detectors improves the recovery of clinically relevant metrics such as the striatal binding ratio and mean activity in selected cerebral structures. Our findings proving the usefulness of the QV ring for brain imaging with 123I agents can be generalized to other commonly used SPECT imaging agents labelled with isotopes, such as 99mTc and likely 111In.

Kinetic characterization of a novel cationic (99m)Tc(I)-tricarbonyl complex, (99m)Tc-15C5-PNP, for myocardial perfusion imaging.

BACKGROUND: Intense liver uptake of (99m)Tc-sestamibi (MIBI) often interferes with visualization of myocardial perfusion in the inferior wall of the left ventricle. To develop improved myocardial perfusion agents, crown ether-containing dithiocarbamates and bisphosphines have been introduced in recent years. This study was designed to investigate the myocardial imaging properties and in vivo kinetics of a cationic (99m)Tc(I)-tricarbonyl complex, (99m)Tc-15C5-PNP, in comparison with MIBI. METHODS: Dynamic cardiac images were acquired for 60 minutes after intravenous tracer injection using a small-animal SPECT system in healthy control rats and rats with myocardial infarcts. Myocardial and liver time-activity curves were generated for radiopharmaceutical kinetic analysis. RESULTS: Good visualization of the left ventricular wall and perfusion defects could be achieved 20 minutes after (99m)Tc-15C5-PNP administration. (99m)Tc-15C5-PNP images in all hearts with infarcts showed perfusion defects, which were comparable to MIBI images. The kinetic curves plotted from 1 to 60 minutes demonstrated that (99m)Tc-15C5-PNP has a shorter washout half-life (6.4 ± 3.2 vs 124 ± 30.5 minutes, P < .01) in the liver, lower residual liver activity (14.5 ± 10.2% vs 36.5 ± 28.9%, P < .01), and higher heart/liver ratio than MIBI. CONCLUSIONS: (99m)Tc-15C5-PNP has potential for rapid myocardial perfusion imaging with low liver uptake.

Maximum-Likelihood Estimation With a Contracting-Grid Search Algorithm.

A fast search algorithm capable of operating in multi-dimensional spaces is introduced. As a sample application, we demonstrate its utility in the 2D and 3D maximum-likelihood position-estimation problem that arises in the processing of PMT signals to derive interaction locations in compact gamma cameras. We demonstrate that the algorithm can be parallelized in pipelines, and thereby efficiently implemented in specialized hardware, such as field-programmable gate arrays (FPGAs). A 2D implementation of the algorithm is achieved in Cell/BE processors, resulting in processing speeds above one million events per second, which is a 20× increase in speed over a conventional desktop machine. Graphics processing units (GPUs) are used for a 3D application of the algorithm, resulting in processing speeds of nearly 250,000 events per second which is a 250× increase in speed over a conventional desktop machine. These implementations indicate the viability of the algorithm for use in real-time imaging applications.

Deep learning based methods for gamma ray interaction location estimation in monolithic scintillation crystal detectors.

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

Investigation of Axial and Angular Sampling in Multi-Detector Pinhole-SPECT Brain Imaging.

We designed a dedicated multi-detector multi-pinhole brain SPECT scanner to generate images of higher quality compared to general-purpose systems. The system, AdaptiSPECT-C, is intended to adapt its sensitivity-resolution trade-off by varying its aperture configurations allowing both high-sensitivity dynamic and high-spatial-resolution static imaging. The current system design consists of 23 detector heads arranged in a truncated spherical geometry. In this work, we investigated the axial and angular sampling capability of the current stationary system design. Two data acquisition schemes using limited rotation of the gantry and two others using axial translation of the imaging bed were also evaluated concerning their impact on image quality through improved sampling. Increasing both angular and axial sampling in the current prototype system resulted in quantitative improvements in image quality metrics and qualitative appearance of the images as determined in studies with specifically selected phantoms. Visual improvements for the brain phantoms with clinical distributions were less pronounced but presented quantitative improvements in the fidelity (normalized root-mean-square error (NRMSE)) and striatal specific binding ratio (SBR) for a dopamine transporter (DAT) distribution, and in NRMSE and activity recovery for a brain perfusion distribution. More pronounced improvements with increased sampling were seen in contrast recovery coefficient, bias, and coefficient of variation for a lesion in the brain perfusion distribution. The negligible impact of the most cranial ring of detectors on axial sampling, but its significant impact on sensitivity and angular sampling in the cranial portion of the imaging volume-of-interest were also determined.

Calibration Method for ML Estimation of 3D Interaction Position in a Thick Gamma-Ray Detector.

High-energy (> 100 keV) photon detectors are often made thick relative to their lateral resolution in order to improve their photon-detection efficiency. To avoid issues of parallax and increased signal variance that result from random interaction depth, we must determine the 3D interaction position in the imaging detector. With this goal in mind, we examine a method of calibrating response statistics of a thick-detector gamma camera to produce a maximum-likelihood estimate of 3D interaction position. We parameterize the mean detector response as a function of 3D position, and we estimate these parameters by maximizing their likelihood given prior knowledge of the pathlength distribution and a complete list of camera signals for an ensemble of gamma-ray interactions. Furthermore, we describe an iterative method for removing multiple-interaction events from our calibration data and for refining our calibration of the mean detector response to single interactions. We demonstrate this calibration method with simulated gamma-camera data. We then show that the resulting calibration is accurate and can be used to produce unbiased estimates of 3D interaction position.