The development of radiation detectors capable of delivering spatial information about gamma-ray interactions was one of the key enabling technologies for nuclear medicine imaging and, eventually, ...single-photon emission computed tomography (SPECT). The continuous sodium iodide scintillator crystal coupled to an array of photomultiplier tubes, almost universally referred to as the Anger Camera after its inventor, has long been the dominant SPECT detector system. Nevertheless, many alternative materials and configurations have been investigated over the years. Technological advances as well as the emerging importance of specialized applications, such as cardiac and preclinical imaging, have spurred innovation such that alternatives to the Anger Camera are now part of commercial imaging systems. Increased computing power has made it practical to apply advanced signal processing and estimation schemes to make better use of the information contained in the detector signals. In this review we discuss the key performance properties of SPECT detectors and survey developments in both scintillator and semiconductor detectors and their readouts with an eye toward some of the practical issues at least in part responsible for the continuing prevalence of the Anger Camera in the clinic.
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 137Cs 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 137Cs 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.
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.
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.
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.
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.
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.
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 of
I-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-like
I-IMP brain perfusion source distributions.
This work enables the simulation of complex SPECT acquisitions and reconstructions for emulating realistic imaging data close to those of actual patients.
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.
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•Imaging of radiolabeled antibody reveals eNAMPT involving in ischemic injury.•Humanized eNAMPT-neutralizing mAb shows anti-fibrotic effects in infarcted hearts.•eNAMPT functions as a DAMP leading to post-infarct cardiac remodeling and heart failure.•eNAMPT/TLR4 inflammatory cascade drives post-infarct cardiac remodeling.•Anti-eNAMPT antibody theranostics provides diagnostic and therapeutic potential.
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.
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
I 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
I agents can be generalized to other commonly used SPECT imaging agents labelled with isotopes, such as
Tc and likely
In.
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