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.

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.

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.

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.

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.

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.

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.

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.

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.

Primary, scatter, and penetration characterizations of parallel-hole and pinhole collimators for I-123 SPECT.

Multi-pinhole (MPH) collimators are known to provide better trade-off between sensitivity and resolution for preclinical, as well as for smaller regions in clinical SPECT imaging compared to conventional collimators. In addition to this geometric advantage, MPH plates typically offer better stopping power for penetration than the conventional collimators, which is especially relevant for I-123 imaging. The I-123 emits a series of high-energy (>300 keV, ~2.5% abundance) gamma photons in addition to the primary emission (159 keV, 83% abundance). Despite their low abundance, high-energy photons penetrate through a low-energy parallel-hole (LEHR) collimator much more readily than the 159 keV photons, resulting in large downscatter in the photopeak window. In this work, we investigate the primary, scatter, and penetration characteristics of a single pinhole collimator that is commonly used for I-123 thyroid imaging and our two MPH collimators designed for I-123 DaTscan imaging for Parkinson's Disease, in comparison to three different parallel-hole collimators through a series of experiments and Monte Carlo simulations. The simulations of a point source and a digital human phantom with DaTscan activity distribution showed that our MPH collimators provide superior count performance in terms of high primary counts, low penetration, and low scatter counts compared to the parallel-hole and single pinhole collimators. For example, total scatter, multiple scatter, and collimator penetration events for the LEHR were 2.5, 7.6 and 14 times more than that of MPH within the 15% photopeak window. The total scatter fraction for LEHR was 56% where the largest contribution came from the high-energy scatter from the back compartments (31%). For the same energy window, the total scatter for MPH was 21% with only 1% scatter from the back compartments. We therefore anticipate that using MPH collimators, higher quality reconstructions can be obtained in a substantially shorter acquisition time for I-123 DaTscan and thyroid imaging.

Fast gamma-ray interaction-position estimation using k-d tree search.

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

Imaging assessment of cardioprotection mediated by a dodecafluoropentane oxygen-carrier administered during myocardial infarction.

INTRODUCTION: The objective of this study was to investigate the cardioprotective effects of a dodecafluoropentane (DDFP)-based perfluorocarbon emulsion (DDFPe) as an artificial carrier for oxygen delivery to ischemic myocardium, using 99mTc-duramycin SPECT imaging. METHODS: Rat hearts with Ischemia-reperfusion (I/R) was prepared by coronary ligation for 45-min followed by reperfusion. The feasibility of 99mTc-duramycin in detecting myocardial I/R injury and its kinetic profile were first verified in the ischemic hearts with 2-h reperfusion (n = 6). DDFPe (0.6 mL/kg) was intravenously administered at 10 min after coronary ligation in fifteen rats and saline was given in thirteen rats as controls. 99mTc-duramycin SPECT images were acquired in the DDFPe-treated hearts and saline controls at 2-h (DDFPe-2 h, n = 7 and Saline-2 h, n = 6) or 24-h (DDFPe-24 h, n = 8 and Saline-24 h, n = 7) of reperfusion. RESULTS: SPECT images, showing "hot-spot" 99mTc-duramycin uptake in the ischemic myocardium, exhibited significantly lower radioactive retention and smaller hot-spot size in the DDFPe-2 h and DDFPe-24 h hearts compared to controls. The infarcts in the Saline-24 h hearts extended significantly relative to measurements in the Saline-2 h. The extension of infarct size did not reach a statistical difference between the DDFPe-2 h and DDFPe-24 h hearts. Ex vivo measurement of 99mTc-duramycin activity (%ID/g) was lower in the ischemic area of DDFPe-2 h and DDFPe-24 h than that of the Saline-2 h and Saline-24 h hearts (P < 0.05). The area of injured myocardium, delineated by the uptake of 99mTc-duramycin, extended more substantially outside the infarct zone in the controls. CONCLUSIONS: Significant reduction in myocardial I/R injury, as assessed by 99mTc-duramycin cell death imaging and histopathological analysis, was induced by DDFPe treatment after acute myocardial ischemia. 99mTc-duramycin imaging can reveal myocardial cell death in ischemic hearts and may provide a tool for the non-invasive assessment of cardioprotective interventions.

A Novel Metal-Based Imaging Probe for Targeted Dual-Modality SPECT/MR Imaging of Angiogenesis.

Superparamagnetic iron oxide nanoparticles with well-integrated multimodality imaging properties have generated increasing research interest in the past decade, especially when it comes to the targeted imaging of tumors. Bevacizumab (BCZM) on the other hand is a well-known and widely applied monoclonal antibody recognizing VEGF-A, which is overexpressed in angiogenesis. The aim of this proof-of-concept study was to develop a dual-modality nanoplatform for in vivo targeted single photon computed emission tomography (SPECT) and magnetic resonance imaging (MRI) of tumor vascularization. Iron oxide nanoparticles (IONPs) have been coated with dimercaptosuccinic acid (DMSA), for consequent functionalization with the monoclonal antibody BCZM radiolabeled with 99mTc, via well-developed surface engineering. The IONPs were characterized based on their size distribution, hydrodynamic diameter and magnetic properties. In vitro cytotoxicity studies showed that our nanoconstruct does not cause toxic effects in normal and cancer cells. Fe3O4-DMSA-SMCC-BCZM-99mTc were successfully prepared at high radiochemical purity (>92%) and their stability in human serum and in PBS were demonstrated. In vitro cell binding studies showed the ability of the Fe3O4-DMSA-SMCC-BCZM-99mTc to bind to the VEGF-165 isoform overexpressed on M-165 tumor cells. The ex vivo biodistribution studies in M165 tumor-bearing SCID mice showed high uptake in liver, spleen, kidney and lungs. The Fe3O4-DMSA-SMCC-BCZM-99mTc demonstrated quick tumor accumulation starting at 8.9 ± 1.88%ID/g at 2 h p.i., slightly increasing at 4 h p.i. (16.21 ± 2.56%ID/g) and then decreasing at 24 h p.i. (6.01 ± 1.69%ID/g). The tumor-to-blood ratio reached a maximum at 24 h p.i. (~7), which is also the case for the tumor-to-muscle ratio (~18). Initial pilot imaging studies on an experimental gamma-camera and a clinical MR camera prove our hypothesis and demonstrate the potential of Fe3O4-DMSA-SMCC-BCZM-99mTc for targeted dual-modality imaging. Our findings indicate that Fe3O4-DMSA-SMCC-BCZM-99mTc IONPs could serve as an important diagnostic tool for biomedical imaging as well as a promising candidate for future theranostic applications in cancer.

Maximum-Likelihood Estimation of Scintillation Pulse Timing.

Including time-of-flight information in positron emission tomography (PET) reconstruction increases the signal-to-noise ratio if the timing information is sufficiently accurate. We estimate timing information by analyzing sampled waveforms, where the sampling frequency and number of samples acquired affect the accuracy of timing estimation. An efficient data-acquisition system acquires the minimum number of samples that contains the most timing information for a desired resolution. We describe a maximum-likelihood (ML) estimation algorithm to assign a time stamp to digital pulses. The method is based on a contracting-grid search algorithm that can be implemented in a field-programmable gate array and in graphics processing units. The Fisher-information (FI) matrix quantifies the amount of timing information that can be extracted from the waveforms. FI analyses on different segments of the waveform allow us to determine the smallest amount of data that we need to acquire in order to obtain a desired timing resolution. We describe the model and the procedure used to simulate waveforms for ML estimation and FI analysis, the ML-estimation algorithm and the timing resolution obtained from experimental data using a LaBr3:Ce crystal and two photomultiplier tubes. The results show that for lengthening segments of the pulse, timing resolution approaches a limit. We explored the method as a function of sampling frequency and compared the results to other digital time pickoff methods. This information will be used to build an efficient data-acquisition system with reduced complexity and cost that nonetheless preserves full timing performance.

An edge-readout, multilayer detector for positron emission tomography.

PURPOSE: We present a novel gamma-ray-detector design based on total internal reflection (TIR) of scintillation photons within a crystal that addresses many limitations of traditional PET detectors. Our approach has appealing features, including submillimeter lateral resolution, DOI positioning from layer thickness, and excellent energy resolution. The design places light sensors on the edges of a stack of scintillator slabs separated by small air gaps and exploits the phenomenon that more than 80% of scintillation light emitted during a gamma-ray event reaches the edges of a thin crystal with polished faces due to TIR. Gamma-ray stopping power is achieved by stacking multiple layers, and DOI is determined by which layer the gamma ray interacts in. METHOD: The concept of edge readouts of a thin slab was verified by Monte Carlo simulation of scintillation light transport. An LYSO crystal of dimensions 50.8 mm × 50.8 mm × 3.0 mm was modeled with five rectangular SiPMs placed along each edge face. The mean-detector-response functions (MDRFs) were calculated by simulating signals from 511 keV gamma-ray interactions in a grid of locations. Simulations were carried out to study the influence of choice of scintillator material and dimensions, gamma-ray photon energies, introduction of laser or mechanically induced optical barriers (LIOBs, MIOBs), and refractive indices of optical-coupling media and SiPM windows. We also analyzed timing performance including influence of gamma-ray interaction position and presence of optical barriers. We also modeled and built a prototype detector, a 27.4 mm × 27.4 mm × 3.0 mm CsI(Tl) crystal with 4 SiPMs per edge to experimentally validate the results predicted by the simulations. The prototype detector used CsI(Tl) crystals from Proteus outfitted with 16 Hamamatsu model S13360-6050PE MPPCs read out by an AiT-16-channel readout. The MDRFs were measured by scanning the detector with a collimated beam of 662-keV photons from a 137 Cs source. The spatial resolution was experimentally determined by imaging a tungsten slit that created a beam of 0.44 mm (FWHM) width normal to the detector surface. The energy resolution was evaluated by analyzing list-mode data from flood illumination by the 137 Cs source. RESULT: We find that in a block-detector-sized LYSO layer read out by five SiPMs per edge, illuminated by 511-keV photons, the average resolution is 1.49 mm (FWHM). With the introduction of optical barriers, average spatial resolution improves to 0.56 mm (FWHM). The DOI resolution is the layer thickness of 3.0 mm. We also find that optical-coupling media and SiPM-window materials have an impact on spatial resolution. The timing simulation with LYSO crystal yields a coincidence resolving time (CRT) of 200-400 ps, which is slightly position dependent. And the introduction of optical barriers has minimum influence. The prototype CsI(Tl) detector, with a smaller area and fewer SiPMs, was measured to have central-area spatial resolutions of 0.70 and 0.39 mm without and with optical barriers, respectively. These results match well with our simulations. An energy resolution of 6.4% was achieved at 662 keV. CONCLUSION: A detector design based on a stack of monolithic scintillator layers that uses edge readouts offers several advantages over current block detectors for PET. For example, there is no tradeoff between spatial resolution and detection sensitivity since no reflector material displaces scintillator crystal, and submillimeter resolution can be achieved. DOI information is readily available, and excellent timing and energy resolutions are possible.