SPECT/CT imaging of inflammation and calcification in human carotid atherosclerosis to identify the plaque at risk of rupture.

BACKGROUND: Calcification and inflammation are atherosclerotic plaque compositional biomarkers that have both been linked to stroke risk. The aim of this study was to evaluate their co-existing prevalence in human carotid plaques with respect to plaque phenotype to determine the value of hybrid imaging for the detection of these biomarkers. METHODS: Human carotid plaque segments, obtained from endarterectomy, were incubated in [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt), targeting Leukocyte Function-associated Antigen-1 (LFA-1) on leukocytes. By performing SPECT/CT, both inflammation from DANBIRT uptake and calcification from CT imaging were assessed. Plaque phenotype was classified using histology. RESULTS: On a total plaque level, comparable levels of calcification volume existed with different degrees of inflammation and vice versa. On a segment level, an inverse relationship between calcification volume and inflammation was evident in highly calcified segments, which classify as fibrocalcific, stable plaque segments. In contrast, segments with little or no calcification presented with a moderate to high degree of inflammation, often coinciding with the more dangerous fibrous cap atheroma phenotype. CONCLUSION: Calcification imaging alone can only accurately identify highly calcified, stable, fibrocalcific plaques. To identify high-risk plaques, with little or no calcification, hybrid imaging of calcification and inflammation could provide diagnostic benefit.

Positron range-free and multi-isotope tomography of positron emitters.

Despite improvements in small animal PET instruments, many tracers cannot be imaged at sufficiently high resolutions due to positron range, while multi-tracer PET is hampered by the fact that all annihilation photons have equal energies. Here we realize multi-isotope and sub-mm resolution PET of isotopes with several mm positron range by utilizing prompt gamma photons that are commonly neglected. A PET-SPECT-CT scanner (VECTor/CT, MILabs, The Netherlands) equipped with a high-energy cluster-pinhole collimator was used to image 124I and a mix of 124I and 18F in phantoms and mice. In addition to positrons (mean range 3.4 mm) 124I emits large amounts of 603 keV prompt gammas that-aided by excellent energy discrimination of NaI-were selected to reconstruct 124I images that are unaffected by positron range. Photons detected in the 511 keV window were used to reconstruct 18F images. Images were reconstructed iteratively using an energy dependent matrix for each isotope. Correction of 18F images for contamination with 124I annihilation photons was performed by Monte Carlo based range modelling and scaling of the 124I prompt gamma image before subtracting it from the 18F image. Additionally, prompt gamma imaging was tested for 89Zr that emits very high-energy prompts (909 keV). In Derenzo resolution phantoms 0.75 mm rods were clearly discernable for 124I, 89Zr and for simultaneously acquired 124I and 18F imaging. Image quantification in phantoms with reservoirs filled with both 124I and 18F showed excellent separation of isotopes and high quantitative accuracy. Mouse imaging showed uptake of 124I in tiny thyroid parts and simultaneously injected 18F-NaF in bone structures. The ability to obtain PET images at sub-mm resolution both for isotopes with several mm positron range and for multi-isotope PET adds to many other unique capabilities of VECTor's clustered pinhole imaging, including simultaneous sub-mm PET-SPECT and theranostic high energy SPECT.

In vivo biodistribution of stable spherical and filamentous micelles probed by high-sensitivity SPECT.

Understanding how nanoparticle properties such as size, morphology and rigidity influence their circulation time and biodistribution is essential for the development of nanomedicine therapies. Herein we assess the influence of morphology on cellular internalization, in vivo biodistribution and circulation time of nanocarriers using polystyrene-b-poly(ethylene oxide) micelles of spherical or elongated morphology. The glassy nature of polystyrene guarantees the morphological stability of the carriers in vivo and by encapsulating Indium-111 in their core, an assessment of the longitudinal in vivo biodistribution of the particles in healthy mice is performed with single photon emission computed tomography imaging. Our results show prolonged blood circulation, longer than 24 hours, for all micelle morphologies studied. Dynamics of micelle accumulation in the liver and other organs of the reticuloendothelial system show a size-dependent nature and late stage liver clearance is observed for the elongated morphology. Apparent contradictions between recent similar studies can be resolved by considering the effects of flexibility and degradation of the elongated micelles on their circulation time and biodistribution.

Similarity-regulation of OS-EM for accelerated SPECT reconstruction.

Ordered subsets expectation maximization (OS-EM) is widely used to accelerate image reconstruction in single photon emission computed tomography (SPECT). Speedup of OS-EM over maximum likelihood expectation maximization (ML-EM) is close to the number of subsets used. Although a high number of subsets can shorten reconstruction times significantly, it can also cause severe image artifacts such as improper erasure of reconstructed activity if projections contain few counts. We recently showed that such artifacts can be prevented by using a count-regulated OS-EM (CR-OS-EM) algorithm which automatically adapts the number of subsets for each voxel based on the estimated number of counts that the voxel contributed to the projections. While CR-OS-EM reached high speed-up over ML-EM in high-activity regions of images, speed in low-activity regions could still be very slow. In this work we propose similarity-regulated OS-EM (SR-OS-EM) as a much faster alternative to CR-OS-EM. SR-OS-EM also automatically and locally adapts the number of subsets, but it uses a different criterion for subset regulation: the number of subsets that is used for updating an individual voxel depends on how similar the reconstruction algorithm would update the estimated activity in that voxel with different subsets. Reconstructions of an image quality phantom and in vivo scans show that SR-OS-EM retains all of the favorable properties of CR-OS-EM, while reconstruction speed can be up to an order of magnitude higher in low-activity regions. Moreover our results suggest that SR-OS-EM can be operated with identical reconstruction parameters (including the number of iterations) for a wide range of count levels, which can be an additional advantage from a user perspective since users would only have to post-filter an image to present it at an appropriate noise level.

Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP.

INTRODUCTION: (188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for adequate bone affinity, but little is known about the optimal carrier concentration. METHODS: We investigated the influence of carrier concentration in the formulation on the radiochemical purity, in-vitro hydroxyapatite affinity and the in-vivo bone accumulation of (188)Rhenium-HEDP in mice. RESULTS: The carrier concentration influenced hydroxyapatite binding in-vitro as well as bone accumulation in-vivo. Variation in hydroxyapatite binding with various carrier concentrations seemed to be mainly driven by variation in radiochemical purity. The in-vivo bone accumulation appeared to be more complex: satisfactory radiochemical purity and hydroxyapatite affinity did not necessarily predict acceptable bio-distribution of (188)Rhenium-HEDP. CONCLUSIONS: For development of new bisphosphonate-based radiopharmaceuticals for clinical use, human administration should not be performed without previous animal bio-distribution experiments. Furthermore, our clinical formulation of (188)Rhenium-HEDP, containing 10 µmol carrier, showed excellent bone accumulation that was comparable to other bisphosphonate-based radiopharmaceuticals, with no apparent uptake in other organs. ADVANCES IN KNOWLEDGE: Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo. IMPLICATIONS FOR PATIENT CARE: The formulation for (188)Rhenium-HEDP as developed by us for clinical use exhibits excellent bone uptake and variation in carrier concentration during preparation of this radiopharmaceutical should be avoided.

Improved EMCCD gamma camera performance by SiPM pre-localization.

High spatial resolution γ-imaging can be achieved with scintillator readout by low-noise, fast, electron-multiplying charge-coupled devices (EMCCDs). Previously we have shown that false-positive events due to EMCCD noise can be rejected by using the sum signal from silicon photomultipliers (SiPMs) mounted on the sides of the scintillator. Here we launch a next generation hybrid CCD-SiPM camera that utilizes the individual SiPM signals and maximum likelihood estimation (MLE) pre-localization of events to discriminate between true and false events in CCD frames. In addition, SiPM signals are utilized for improved energy discrimination. The performance of this hybrid detector was tested for a continuous CsI:Tl crystal at 140 keV. With a pre-localization accuracy of 1.06 mm (full-width-at-half-maximum) attained with MLE the signal-to-background ratio (SBR) was improved by a factor of 5.9, 4.0 or 2.2 compared to the EMCCD-only readout, at the cost of rejecting, respectively, 47%, 9% or 4% of the events. Combining the pre-localization and SiPM energy estimation improved the energy resolution from 50% to (19 ± 3)% while maintaining the spatial resolution at 180 µm.

Quantitative multi-pinhole small-animal SPECT: uniform versus non-uniform Chang attenuation correction.

Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. We propose a Chang-based non-uniform attenuation correction (NUA-CT) for small-animal SPECT/CT with focusing pinhole collimation, and compare the quantitative accuracy with uniform Chang correction based on (i) body outlines extracted from x-ray CT (UA-CT) and (ii) on hand drawn body contours on the images obtained with three integrated optical cameras (UA-BC). Measurements in phantoms and rats containing known activities of isotopes were conducted for evaluation. In (125)I, (201)Tl, (99m)Tc and (111)In phantom experiments, average relative errors comparing to the gold standards measured in a dose calibrator were reduced to 5.5%, 6.8%, 4.9% and 2.8%, respectively, with NUA-CT. In animal studies, these errors were 2.1%, 3.3%, 2.0% and 2.0%, respectively. Differences in accuracy on average between results of NUA-CT, UA-CT and UA-BC were less than 2.3% in phantom studies and 3.1% in animal studies except for (125)I (3.6% and 5.1%, respectively). All methods tested provide reasonable attenuation correction and result in high quantitative accuracy. NUA-CT shows superior accuracy except for (125)I, where other factors may have more impact on the quantitative accuracy than the selected attenuation correction.

An efficient simulator for pinhole imaging of PET isotopes.

Today, small-animal multi-pinhole single photon emission computed tomography (SPECT) can reach sub-half-millimeter image resolution. Recently we have shown that dedicated multi-pinhole collimators can also image PET tracers at sub-mm level. Simulations play a vital role in the design and optimization of such collimators. Here we propose and validate an efficient simulator that models the whole imaging chain from emitted positron to detector signal. This analytical simulator for pinhole positron emission computed tomography (ASPECT) combines analytical models for pinhole and detector response with Monte Carlo (MC)-generated kernels for positron range. Accuracy of ASPECT was validated by means of a MC simulator (MCS) that uses a kernel-based step for detector response with an angle-dependent detector kernel based on experiments. Digital phantom simulations with ASPECT and MCS converge to almost identical images. However, ASPECT converges to an equal image noise level three to four orders of magnitude faster than MCS. We conclude that ASPECT could serve as a practical tool in collimator design and iterative image reconstruction for novel multi-pinhole PET.

An enhanced high-resolution EMCCD-based gamma camera using SiPM side detection.

Electron-multiplying charge-coupled devices (EMCCDs) coupled to scintillation crystals can be used for high-resolution imaging of gamma rays in scintillation counting mode. However, the detection of false events as a result of EMCCD noise deteriorates the spatial and energy resolution of these gamma cameras and creates a detrimental background in the reconstructed image. In order to improve the performance of an EMCCD-based gamma camera with a monolithic scintillation crystal, arrays of silicon photon-multipliers (SiPMs) can be mounted on the sides of the crystal to detect escaping scintillation photons, which are otherwise neglected. This will provide a priori knowledge about the correct number and energies of gamma interactions that are to be detected in each CCD frame. This information can be used as an additional detection criterion, e.g. for the rejection of otherwise falsely detected events. The method was tested using a gamma camera based on a back-illuminated EMCCD, coupled to a 3 mm thick continuous CsI:Tl crystal. Twelve SiPMs have been mounted on the sides of the CsI:Tl crystal. When the information of the SiPMs is used to select scintillation events in the EMCCD image, the background level for (99m)Tc is reduced by a factor of 2. Furthermore, the SiPMs enable detection of (125)I scintillations. A hybrid SiPM-/EMCCD-based gamma camera thus offers great potential for applications such as in vivo imaging of gamma emitters.

Theoretical analysis of full-ring multi-pinhole brain SPECT.

Presently used clinical brain SPECT suffers from limited spatio-temporal resolution. Here we investigate the feasibility of high-resolution and high-sensitivity full-ring multi-pinhole brain SPECT (MP-SPECT). Using an analytical model we optimized pinhole-detector geometries of MP-SPECT for different detector intrinsic resolutions R(i). System resolution and sensitivity of optimized MP-SPECT were compared to conventional clinical SPECT. The comparison of the system resolution of different systems was done at matched sensitivity, which was achieved by tuning pinhole diameters. Similarly, sensitivities were compared at matched system resolution. For MP-SPECT that uses detectors with intrinsic resolutions of 4 mm > R(i) 0.5 mm a sensitivity can be achieved that is 6.0 times higher than the sensitivity of conventional dual-head SPECT systems with parallel-hole collimators (DualPar), while system resolution can be improved by a factor of 2.4. To achieve these improvements a large detector-to-collimator distance is needed. In contrast, for detectors with intrinsic resolutions <0.2 mm, it is beneficial to place the detectors close to the pinholes, resulting in a high number of de-magnified projections. For a detector intrinsic resolution of 0.05 mm, a 14.5-fold improvement in sensitivity and a 3.8-fold improvement in system resolution compared to DualPar is predicted. Furthermore, we found that for optimized MP-SPECT the sensitivity scales proportionally to system resolution squared, with the proportionality constant depending on R(i). From our sensitivity-system resolution trade-off equations we deduced that MP-SPECT with an ideal detector (R(i) --> 0) can have a system resolution that is 2.0 times better than optimized MP-SPECT with a conventional detector (R(i) approximately 3 mm). The high performance of optimized MP-SPECT may open up completely new molecular imaging applications.

Movies of dopamine transporter occupancy with ultra-high resolution focusing pinhole SPECT.

A pivotal question in neuropharmacology is how the function of neurotransmitter systems relates to psychiatric diseases. In experimental neuropharmacology, we have dreamt about a looking glass that would allow us to see neurotransmitter systems in action, and about animals that would faithfully serve us as models for human psychiatric disease. Analysis of animal models has been limited by the availability of methods to study in vivo neurotransmitter dynamics. Now, a single photon emission computed tomography system called U-SPECT can localize dopamine transporters in sub-compartments of the mouse brain during a range of points in time. Applied to the midbrain dopamine system of different models of disease, this will aid the understanding of dynamic processes of this neurotransmitter that underlie brain functions and human brain pathology.

Optimizing multi-pinhole SPECT geometries using an analytical model.

State-of-the-art multi-pinhole SPECT devices allow for sub-mm resolution imaging of radio-molecule distributions in small laboratory animals. The optimization of multi-pinhole and detector geometries using simulations based on ray-tracing or Monte Carlo algorithms is time-consuming, particularly because many system parameters need to be varied. As an efficient alternative we develop a continuous analytical model of a pinhole SPECT system with a stationary detector set-up, which we apply to focused imaging of a mouse. The model assumes that the multi-pinhole collimator and the detector both have the shape of a spherical layer, and uses analytical expressions for effective pinhole diameters, sensitivity and spatial resolution. For fixed fields-of-view, a pinhole-diameter adapting feedback loop allows for the comparison of the system resolution of different systems at equal system sensitivity, and vice versa. The model predicts that (i) for optimal resolution or sensitivity the collimator layer with pinholes should be placed as closely as possible around the animal given a fixed detector layer, (ii) with high-resolution detectors a resolution improvement up to 31% can be achieved compared to optimized systems, (iii) high-resolution detectors can be placed close to the collimator without significant resolution losses, (iv) interestingly, systems with a physical pinhole diameter of 0 mm can have an excellent resolution when high-resolution detectors are used.

Evaluation of accelerated iterative x-ray CT image reconstruction using floating point graphics hardware.

Statistical reconstruction methods offer possibilities to improve image quality as compared with analytical methods, but current reconstruction times prohibit routine application in clinical and micro-CT. In particular, for cone-beam x-ray CT, the use of graphics hardware has been proposed to accelerate the forward and back-projection operations, in order to reduce reconstruction times. In the past, wide application of this texture hardware mapping approach was hampered owing to limited intrinsic accuracy. Recently, however, floating point precision has become available in the latest generation commodity graphics cards. In this paper, we utilize this feature to construct a graphics hardware accelerated version of the ordered subset convex reconstruction algorithm. The aims of this paper are (i) to study the impact of using graphics hardware acceleration for statistical reconstruction on the reconstructed image accuracy and (ii) to measure the speed increase one can obtain by using graphics hardware acceleration. We compare the unaccelerated algorithm with the graphics hardware accelerated version, and for the latter we consider two different interpolation techniques. A simulation study of a micro-CT scanner with a mathematical phantom shows that at almost preserved reconstructed image accuracy, speed-ups of a factor 40 to 222 can be achieved, compared with the unaccelerated algorithm, and depending on the phantom and detector sizes. Reconstruction from physical phantom data reconfirms the usability of the accelerated algorithm for practical cases.

Parallel statistical image reconstruction for cone-beam x-ray CT on a shared memory computation platform.

Statistical reconstruction methods offer possibilities of improving image quality as compared to analytical methods, but current reconstruction times prohibit routine clinical applications. To reduce reconstruction times we have parallelized a statistical reconstruction algorithm for cone-beam x-ray CT, the ordered subset convex algorithm (OSC), and evaluated it on a shared memory computer. Two different parallelization strategies were developed: one that employs parallelism by computing the work for all projections within a subset in parallel, and one that divides the total volume into parts and processes the work for each sub-volume in parallel. Both methods are used to reconstruct a three-dimensional mathematical phantom on two different grid densities. The reconstructed images are binary identical to the result of the serial (non-parallelized) algorithm. The speed-up factor equals approximately 30 when using 32 to 40 processors, and scales almost linearly with the number of cpus for both methods. The huge reduction in computation time allows us to apply statistical reconstruction to clinically relevant studies for the first time.

Evaluation of the ordered subset convex algorithm for cone-beam CT.

Statistical methods for image reconstruction such as maximum likelihood expectation maximization (ML-EM) are more robust and flexible than analytical inversion methods and allow for accurate modelling of the photon transport and noise. Statistical reconstruction is prohibitively slow when applied to clinical x-ray cone-beam CT due to the large data sets and the high number of iterations required for reconstructing high resolution images. One way to reduce the reconstruction time is to use ordered subsets of projections during the iterations, which has been successfully applied to fan-beam x-ray CT. In this paper, we quantitatively analyse the use of ordered subsets in concert with the convex algorithm for cone-beam x-ray CT reconstruction, for the case of circular acquisition orbits. We focus on the reconstructed image accuracy of a 3D head phantom. Acceleration factors larger than 300 were obtained with errors smaller than 1%, with the preservation of signal-to-noise ratio. Pushing the acceleration factor towards 600 by using an increasing number of subsets increases the reconstruction error up to 5% and significantly increases noise. The results indicate that the use of ordered subsets can be extremely useful for cone-beam x-ray CT.

Experimental validation of a rapid Monte Carlo based micro-CT simulator.

We describe a newly developed, accelerated Monte Carlo simulator of a small animal micro-CT scanner. Transmission measurements using aluminium slabs are employed to estimate the spectrum of the x-ray source. The simulator incorporating this spectrum is validated with micro-CT scans of physical water phantoms of various diameters, some containing stainless steel and Teflon rods. Good agreement is found between simulated and real data: normalized error of simulated projections, as compared to the real ones, is typically smaller than 0.05. Also the reconstructions obtained from simulated and real data are found to be similar. Thereafter, effects of scatter are studied using a voxelized software phantom representing a rat body. It is shown that the scatter fraction can reach tens of per cents in specific areas of the body and therefore scatter can significantly affect quantitative accuracy in small animal CT imaging.

Accelerated simulation of cone beam X-ray scatter projections.

Monte Carlo (MC) methods can accurately simulate scatter in X-ray imaging. However, when low noise scatter projections have to be simulated these MC simulations tend to be very time consuming. Rapid computation of scatter estimates is essential for several applications. The aim of the work presented in this paper is to speed up the estimation of noise-free scatter projections while maintaining their accuracy. Since X-ray scatter projections are often rather smooth, an approach is chosen whereby a short MC simulation is combined with a data fitting program that is robust to projection truncation and noise. This method allows us to estimate the smooth scatter projection rapidly. The speed-up and accuracy achieved by using the fitting algorithm were validated for the projection simulation of a small animal X-ray CT system. The acceleration that can be obtained over standard MC simulations is typically two orders of magnitude, depending on the accuracy required. The proposed approach may be useful for rapid simulation of patient and animal studies and for correction of the image-degrading effects of scatter in tomography.

Simultaneous (99m)Tc/(201)Tl dual-isotope SPET with Monte Carlo-based down-scatter correction.

In simultaneous technetium-99m/thallium-201 dual-isotope (DI) single-photon emission tomography (SPET), down-scatter of (99m)Tc photons contaminates the (201)Tl image, which leads to a decrease in lesion contrast and loss of quantitative accuracy. Correction for down-scatter can be achieved by first reconstructing the (99m)Tc activity distribution. Subsequently, the (99m)Tc down-scatter in the (201)Tl photopeak window is simulated and used for correction during iterative reconstruction of the (201)Tl image. In this work, the down-scatter projections are calculated using a dedicated Monte Carlo simulator which is able to efficiently model the detection of lead X-rays from the collimator. An anthropomorphic torso phantom with a cardiac insert with and without cold lesions was used for evaluation of the proposed method. Excellent agreement in lesion contrast and quantitative accuracy was found between the down-scatter corrected DI-SPET (201)Tl image and the virgin (i.e. separately acquired) (201)Tl image, in particular when the effects of lead X-rays were included. Compensation for the noise added by down-scatter to the (201)Tl image can be achieved by using a 15% lower dose of (99m)Tc, a 15% increase in scan time and a 12% increase in (201)Tl dose. In conclusion, the Monte Carlo-based down-scatter correction recovers lesion contrast and quantitative accuracy in DI-SPET (201)Tl images almost perfectly. In addition, degradations due to the added noise of down-scatter in simultaneous DI-SPET can be prevented by slight adaptations to the data acquisition protocol.

Rapid SPECT simulation of downscatter in non-uniform media.

A rotation-based Monte Carlo (MC) simulation method (RMC) has been developed, designed for rapid calculation of downscatter through non-uniform media in SPECT. A possible application is downscatter correction in dual isotope SPECT. With RMC, only a fraction of all projections of a SPECT study have to be MC simulated in a standard manner. The other projections can be estimated rapidly using the results of these standard MC calculations. For efficiency, approximations have to be made in RMC with regard to the final scatter angle of the detected photons. Further speed-up is obtained by combining RMC with convolution-based forced detection (CFD) instead of forced detection (FD), which is a more common variance reduction technique for MC. The RMC method was compared with standard MC for 99mTc downscatter in a 201Tl window (72 keV+/-10%) using a digital thorax phantom. The resulting scatter projections are in good agreement (maximum bias a few per cent of the largest value in the projection), but RMC with CFD is about three orders in magnitude faster than standard MC with FD and up to 25 times faster than standard MC with CFD. Using RMC combined with CFD, the generation of 64 almost noise-free downscatter projections (64 x 64) takes only a couple of minutes on a 500 MHz Pentium processor. Therefore, rotation-based Monte Carlo could serve as a practical tool for downscatter correction schemes in dual isotope SPECT.

Choice of collimator for cardiac SPET when resolution compensation is included in iterative reconstruction.

In clinical cardiac single-photon emission tomography (SPET) studies, collimators of different spatial resolution and geometric efficiency are available for imaging. In selecting the appropriate collimator for clinical use, there is a trade-off between spatial resolution, which can limit the contrast of the reconstructed image, and detection efficiency, which determines the noise in the image. Our objective was to assess which collimator is best suited for cardiac SPET when reconstruction is performed with and without compensation for distance-dependent resolution (CDR). The dynamic MCAT thorax phantom was used to simulate 180 degree technetium-99m cardiac data, acquired using either a general-purpose (GP) or high-resolution (HR) collimator. For GP and HR, the resolution at 15 cm was 11.5 mm and 9.5 mm respectively, and the corresponding relative efficiency was 1.0 and 0.52 respectively. Distance-dependent resolution, attenuation and noise were included in the projection data; scatter was not included. Ordered subsets expectation maximisation reconstruction (subset size 4) was performed with and without CDR. Results were evaluated by comparing the myocardial recovery coefficient and contrast between myocardium and ventricle relative to the original phantom, each plotted for different noise levels corresponding to increasing iteration number. The study demonstrated that, without CDR, HR gave the best results. However, for any given noise level with CDR, GP gave superior recovery and contrast. These findings were confirmed in a physical phantom study. Results suggest that improved reconstruction can be achieved using a GP collimator in combination with resolution compensation.