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.

Observer studies of image quality of denoising reduced-count cardiac single photon emission computed tomography myocardial perfusion imaging by three-dimensional Gaussian post-reconstruction filtering and deep learning.

BACKGROUND: The aim of this research was to asses perfusion-defect detection-accuracy by human observers as a function of reduced-counts for 3D Gaussian post-reconstruction filtering vs deep learning (DL) denoising to determine if there was improved performance with DL. METHODS: SPECT projection data of 156 normally interpreted patients were used for these studies. Half were altered to include hybrid perfusion defects with defect presence and location known. Ordered-subset expectation-maximization (OSEM) reconstruction was employed with the optional correction of attenuation (AC) and scatter (SC) in addition to distance-dependent resolution (RC). Count levels varied from full-counts (100%) to 6.25% of full-counts. The denoising strategies were previously optimized for defect detection using total perfusion deficit (TPD). Four medical physicist (PhD) and six physician (MD) observers rated the slices using a graphical user interface. Observer ratings were analyzed using the LABMRMC multi-reader, multi-case receiver-operating-characteristic (ROC) software to calculate and compare statistically the area-under-the-ROC-curves (AUCs). RESULTS: For the same count-level no statistically significant increase in AUCs for DL over Gaussian denoising was determined when counts were reduced to either the 25% or 12.5% of full-counts. The average AUC for full-count OSEM with solely RC and Gaussian filtering was lower than for the strategies with AC and SC, except for a reduction to 6.25% of full-counts, thus verifying the utility of employing AC and SC with RC. CONCLUSION: We did not find any indication that at the dose levels investigated and with the DL network employed, that DL denoising was superior in AUC to optimized 3D post-reconstruction Gaussian filtering.

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.

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.

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.

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.

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.

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.

Performance analysis of a high-sensitivity multi-pinhole cardiac SPECT system with hemi-ellipsoid detectors.

PURPOSE: Single-photon emission computed tomography (SPECT) is a noninvasive imaging modality, used in myocardial perfusion imaging. The challenges facing the majority of clinical SPECT systems are low sensitivity, poor resolution, and the relatively high radiation dose to the patient. New generation systems (GE Discovery, DSPECT) dedicated to cardiac imaging improve sensitivity by a factor of 5-8. This improvement can be used to decrease acquisition time and/or dose. However, in the case of ultra-low dose (~3 mCi) injections, acquisition times are still significantly long, taking 10-12 min. The purpose of this work is to investigate a new gamma camera design with 21 hemi-ellipsoid detectors each with a pinhole collimator for cardiac SPECT for further improvement in sensitivity and resolution and reduced patient exposures and imaging times. METHODS: To evaluate the resolution of our hemi-ellipsoid system, GATE Monte-Carlo simulations were performed on point-sources, rod-sources, and NCAT phantoms. For average full-width-half-maximum (FWHM) equivalence with base flat-detector, the pinhole-diameter for the curved hemi-ellipsoid detector was found to be 8.68 mm, an operating pinhole-diameter nominally expected to be ~3 times more sensitive than state-of-the-art systems. Rod-sources equally spaced within the region of interest were acquired with a 21-detector system and reconstructed with our multi-pinhole (MPH) iterative OSEM algorithm with collimator resolution recovery. The results were compared with the results of a state-of-the-art system (GE Discovery) available in the literature. The system was also evaluated using the mathematical anthropomorphic NCAT (NURBS-based Cardiac Torso; Segars et al. IEEE Trans Nucl Sci. 1999;46:503-506) phantom with a full (clinical)-dose acquisition (25 mCi) for 2 min and an ultra-low dose acquisition of 3 mCi for 5.44 min. The estimated left ventricle (LV) counts were compared with the available literature on a state-of-the-art system (DSPECT). FWHM of the LV wall on MPH-OSEM-reconstructed images with collimator resolution recovery was estimated. RESULTS: On acquired rod-sources, the average resolution (FWHM) after reconstruction with resolution recovery in the entire region of interest (ROI) for cardiac imaging was on the average 4.44 mm (±2.84), compared to 6.9 mm (±1 mm) reported for GE Discovery (Kennedy et al., J Nucl Cardiol. 2014:21:443-452). For NCAT studies, improved sensitivity allowed a full-dose (25 mCi) 2-min acquisition (Ell8.68mmFD) which yielded 3.79 M LV counts. This is ~3.35 times higher compared to 1.13 M LV counts acquired in 2 min for clinical full dose for state-of-the-art DSPECT. The increased sensitivity also allowed an ultra-low dose acquisition protocol (Ell8.68 mmULD), 3 mCi (eight times less injected dose) in 5.44 min. This ultra-low dose protocol yielded ~1.23 M LV counts which was comparable to the full-dose 2-min acquisition for DSPECT. The estimated NCAT average FWHM at the LV wall after 12 iterations of the OSEM reconstruction was 4.95 and 5.66 mm around the mid-short-axis slices for Ell8.68mmFD and Ell8.68mmULD, respectively. CONCLUSION: Our Monte-Carlo simulation studies and reconstruction suggest using (inverted wineglass sized) hemi-ellipsoid detectors with pinhole collimators can increase the sensitivity ~3.35 times over the new generation of dedicated cardiac SPECT systems, while also improving the reconstructed resolution for rod-sources with an average of 4.44 mm in region of interest. The extra sensitivity may be used for ultra-low dose imaging (3 mCi) at ~5.44 min for comparable clinical counts as state-of-the-art systems.

Simulations of a Multi-Pinhole SPECT Collimator for Clinical Dopamine Transporter (DAT) Imaging.

SPECT imaging of the dopamine transporter (DAT) is used for diagnosis and monitoring progression of Parkinson's Disease (PD), and differentiation of PD from other neurological disorders. The diagnosis is based on the DAT binding in the caudate and putamen structures in the striatum. We previously proposed a relatively inexpensive method to improve the detection and quantification of these structures for dual-head SPECT by replacing one of the fan-beam collimators with a specially designed multi-pinhole (MPH) collimator. In this work, we developed a realistic model of the proposed MPH system using the GATE simulation package and verified the geometry with an analytic simulator. Point source projections from these simulations closely matched confirming the accuracy of the pinhole geometries. The reconstruction of a hot-rod phantom showed that 4.8 mm resolution is achievable. The reconstructions of the XCAT brain phantom showed clear separation of the putamen and caudate, which is expected to improve the quantification of DAT imaging and PD diagnosis. Using this GATE model, point spread functions modeling physical factors will be generated for use in reconstruction. Also, further improvements in geometry are being investigated to increase the sensitivity of this base system while maintaining a target spatial resolution of 4.5-5 mm.

New compartment model analysis of lean-mass and fat-mass growth with overfeeding.

OBJECTIVES: Mathematical models of lean- and fat-mass growth with diet are useful to help describe and potentially predict the fat- and lean-mass change with different diets as a function of consumed protein and fat calories. Most of the existing models do not explicitly account for interdependence of fat-mass on the lean-mass and vice versa. The aim of this study was to develop a new compartmental model to describe the growth of lean and fat mass depending on the input of dietary protein and fat, and accounting for the interdependence of adipose tissue and muscle growth. METHODS: The model was fitted to existing clinical data of an overfeeding trial for 23 participants (with a high-protein diet, a normal-protein diet, and a low-protein diet) and compared with the existing Forbes model. RESULTS: Qualitatively and quantitatively, the compartment model data fit was smoother with less overall error than the Forbes model. The root means square error were 0.39, 0.93 and 0.72 kg for the new model, the Forbes model, and the modified Forbes model, respectively. Additionally, for the present model, the differences between some of the coefficients (on the cross dependence of fat and lean mass as well as on the intake diet dependence) across different diets were statistically significant (P < 0.05). CONCLUSIONS: Our new Dey-model showed excellent fit to overfeeding data for 23 normal participants with some significant differences of model coefficients across diets, enabling further studies of the model coefficients for larger groups of participants with obesity or other diseases.

Investigation of energy weighting using an energy discriminating photon counting detector for breast CT.

PURPOSE: Breast CT is an emerging imaging technique that can portray the breast in 3D and improve visualization of important diagnostic features. Early clinical studies have suggested that breast CT has sufficient spatial and contrast resolution for accurate detection of masses and microcalcifications in the breast, reducing structural overlap that is often a limiting factor in reading mammographic images. For a number of reasons, image quality in breast CT may be improved by use of an energy resolving photon counting detector. In this study, the authors investigate the improvements in image quality obtained when using energy weighting with an energy resolving photon counting detector as compared to that with a conventional energy integrating detector. METHODS: Using computer simulation, realistic CT images of multiple breast phantoms were generated. The simulation modeled a prototype breast CT system using an amorphous silicon (a-Si), CsI based energy integrating detector with different x-ray spectra, and a hypothetical, ideal CZT based photon counting detector with capability of energy discrimination. Three biological signals of interest were modeled as spherical lesions and inserted into breast phantoms; hydroxyapatite (HA) to represent microcalcification, infiltrating ductal carcinoma (IDC), and iodine enhanced infiltrating ductal carcinoma (IIDC). Signal-to-noise ratio (SNR) of these three lesions was measured from the CT reconstructions. In addition, a psychophysical study was conducted to evaluate observer performance in detecting microcalcifications embedded into a realistic anthropomorphic breast phantom. RESULTS: In the energy range tested, improvements in SNR with a photon counting detector using energy weighting was higher (than the energy integrating detector method) by 30%-63% and 4%-34%, for HA and IDC lesions and 12%-30% (with Al filtration) and 32%-38% (with Ce filtration) for the IIDC lesion, respectively. The average area under the receiver operating characteristic curve (AUC) for detection of microcalcifications was higher by greater than 19% (for the different energy weighting methods tested) as compared to the AUC obtained with an energy integrating detector. CONCLUSIONS: This study showed that breast CT with a CZT photon counting detector using energy weighting can provide improvements in pixel SNR, and detectability of microcalcifications as compared to that with a conventional energy integrating detector. Since a number of degrading physical factors were not modeled into the photon counting detector, this improvement should be considered as an upper bound on achievable performance.

Evaluation of lot-to-lot repeatability and effect of assay media choice in the recombinant Factor C assay.

Measurement of environmental endotoxin exposures is complicated by variability encountered using current biological assay methods arising in part from lot-to-lot variability of the Limulus-amebocyte lysate (LAL) reagents. Therefore, we investigated the lot-to-lot repeatability of commercially available recombinant Factor C (rFC) kits as an alternative to LAL. Specifically, we compared endotoxin estimates obtained from rFC assay of twenty indoor dust samples, using four different extraction and assay media, to endotoxin estimates previously obtained by Limulus amebocyte lysate (LAL) assay and amounts of 3-hydroxy fatty acids (3-OHFA) in lipopolysaccharide (LPS) using gas-chromatography mass spectroscopy (GC-MS). We found that lot-to-lot variability of the rFC assay kits does not significantly alter endotoxin estimates in house dust samples when performed using three of the four assay media tested and that choice of assay media significantly altered endotoxin estimates obtained by rFC assay of house dust samples. Our findings demonstrate lot-to-lot reproducibility of rFC assay of environmental samples and suggest that use of rFC assay performed with Tris buffer or water as the extraction and assay medium for measurement of endotoxin in dust samples may be a suitable choice for developing a standardized methodology.