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Microscopic nuclear imaging down to spatial resolutions of a few hundred microns can already be achieved using low-energy gamma emitters (e.g. 125I, ∼30 keV) and a basic single micro-pinhole gamma camera. This has been applied to in vivo mouse thyroid imaging, for example. For clinically used radionuclides such as 99mTc, this approach fails due to penetration of the higher-energy gamma photons through the pinhole edges. To overcome these resolution degradation effects, we propose a new imaging approach: scanning focus nuclear microscopy (SFNM). We assess SFNM using Monte Carlo simulations for clinically used isotopes. SFNM is based on the use of a 2D scanning stage with a focused multi-pinhole collimator containing 42 pinholes with narrow pinhole aperture opening angles to reduce photon penetration. All projections of different positions are used to iteratively reconstruct a three-dimensional image from which synthetic planar images are generated. SFNM imaging was tested using a digital Derenzo resolution phantom and a mouse ankle joint phantom containing 99mTc (140 keV). The planar images were compared with those obtained using a single-pinhole collimator, either with matched pinhole diameter or with matched sensitivity. The simulation results showed an achievable 99mTc image resolution of 0.04 mm and detailed 99mTc bone images of a mouse ankle with SFNM. SFNM has strong advantages over single-pinhole imaging in terms of spatial resolution.

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.

SPECT imaging with 123I-FP-CIT is used for diagnosis of neurodegenerative disorders like Parkinson’s disease. Attenuation correction (AC) can be useful for quantitative analysis of 123I-FP-CIT SPECT. Ideally, AC would be performed based on attenuation maps ( μ -maps) derived from perfectly registered CT scans. Such μ -maps, however, are most times not available and possible errors in image registration can induce quantitative inaccuracies in AC corrected SPECT images. Earlier, we showed that a convolutional neural network (CNN) based approach allows to estimate SPECT-aligned μ -maps for full brain perfusion imaging using only emission data. Here we investigate the feasibility of similar CNN methods for axially focused 123I-FP-CIT scans. We tested our approach on a high-resolution multi-pinhole prototype clinical SPECT system in a Monte Carlo simulation study. Three CNNs that estimate μ -maps in a voxel-wise, patch-wise and image-wise manner were investigated. As the added value of AC on clinical 123I-FP-CIT scans is still debatable, the impact of AC was also reported to check in which cases CNN based AC could be beneficial. AC using the ground truth μ -maps (GT-AC) and CNN estimated μ -maps (CNN-AC) were compared with the case when no AC was done (No-AC). Results show that the effect of using GT-AC versus CNN-AC or No-AC on striatal shape and symmetry is minimal. Specific binding ratios (SBRs) from localized regions show a deviation from GT-AC ≤ 2.5% for all three CNN-ACs while No-AC systematically underestimates SBRs by 13.1%. A strong correlation ( r ≥ 0.99) was obtained between GT-AC based SBRs and SBRs from CNN-ACs and No-AC. Absolute quantification (in kBq ml−1) shows a deviation from GT-AC within 2.2% for all three CNN-ACs and of 71.7% for No-AC. To conclude, all three CNNs show comparable performance in accurate μ -map estimation and 123I-FP-CIT quantification. CNN-estimated μ -map can be a promising substitute for CT-based μ -map.

The use of multi-pinhole collimation has enabled ultra-high-resolution imaging of SPECT and PET tracers in small animals. Key for obtaining high-quality images is the use of statistical iterative image reconstruction with accurate energy-dependent photon transport modelling through collimator and detector. This can be incorporated in a system matrix that contains the probabilities that a photon emitted from a certain voxel is detected at a specific detector pixel. Here we introduce a fast Monte-Carlo based (FMC-based) matrix generation method for pinhole imaging that is easy to apply to various radionuclides. The method is based on accelerated point source simulations combined with model-based interpolation to straightforwardly change or combine photon energies of the radionuclide of interest. The proposed method was evaluated for a VECTor PET-SPECT system with (i) a HE-UHR-M collimator and (ii) an EXIRAD-3D 3D autoradiography collimator. Both experimental scans with 99mTc, 111In, and 123I, and simulated scans with 67Ga and 90Y were performed for evaluation. FMC was compared with two currently used approaches, one based on a set of point source measurements with 99mTc (dubbed traditional method), and the other based on an energy-dependent ray-tracing simulation (ray-tracing method). The reconstruction results show better image quality when using FMC-based matrices than when applying the traditional or ray-tracing matrices in various cases. FMC-based matrices generalise better than the traditional matrices when imaging radionuclides with energies deviating too much from the energy used in the calibration and are computationally more efficient for very-high-resolution imaging than the ray-tracing matrices. In addition, FMC has the advantage of easily combining energies in a single matrix which is relevant when imaging radionuclides with multiple photopeak energies (e.g. 67Ga and 111In) or with a continuous energy spectrum (e.g. 90Y). To conclude, FMC is an efficient, accurate, and versatile tool for creating system matrices for ultra-high-resolution pinhole SPECT.

We recently developed a dedicated focusing multi-pinhole collimator for a stationary SPECT system that offers down to 120 µm (or 1.7 nL) spatial resolution SPECT images of cryo-cooled tissue samples (EXIRAD-3D). This collimator is suitable for imaging isotopes that are often used in small animal and diagnostic SPECT such as 125I (27 keV), 201Tl (71 keV), 99mTc (140 keV), and 111In (171 and 245 keV). The goal of the present work is to develop high-resolution pinhole imaging of tissue samples containing isotopes with high-energy photon emissions, for example, therapeutic alpha and beta emitters that co-emit high energy gammas (e.g. 213Bi (440 keV) and 131I (364 keV)) or 511 keV annihilation photons from PET isotopes. To this end, we optimise and evaluate a new high energy small-bore multi-pinhole collimator through simulations. The collimator-geometry was first optimised by simulating a Derenzo phantom scan with a biologically realistic activity concentration of 18F at two system sensitivities (0.30% and 0.60%) by varying pinhole placements. Subsequently, the wall thickness was selected based on reconstructions of a Derenzo phantom and a uniform phantom. The obtained collimators were then evaluated for 131I (364 keV), 213Bi (440 keV), 64Cu (511 keV), and 124I (511 + 603 keV) with biologically realistic activity concentrations, and also for some high activity concentrations of 18F, using digital resolution, mouse knee joint, and xenograft phantoms. Our results show that placing pinhole centres at a distance of 8 mm from the collimator inner wall yields good image quality, while a wall thickness of 43 mm resulted in sufficient shielding. The collimators offer resolutions down to 0.35 mm, 0.6 mm, 0.5 mm, 0.6 mm, and 0.5 mm when imaging 131I, 213Bi, 18F, 64Cu, and 124I, respectively, contained in tissue samples at biologically achievable activity concentrations.

Today, versatile emission computed tomography (VECTor) technology using dedicated high-energy collimation enables simultaneous positron emission tomography (PET) and single photon emission computed tomography (SPECT) down to 0.6 mm and 0.4 mm resolution in mice, respectively. We recently showed that for optimal resolution and quantitative accuracy of PET images the long tails of the 511 keV point spread functions (PSFs) need to be fully modelled during image reconstruction. This, however, leads to very time consuming reconstructions and thus significant acceleration in reconstruction speed is highly desirable. To this end we propose and validate a combined dual-matrix dual-voxel (DM-DV) approach: for the forward projection the slowly varying PSF tails are modelled on a three times rougher voxel grid than the central parts of the PSFs, while in the backprojection only parts of the PSF tails are included. DM-DV reconstruction is implemented in pixel-based ordered subsets expectation maximization (POSEM) and in a recently proposed accelerated pixel-based similarity-regulated ordered subsets expectation maximization (SROSEM). Both a visual assessment and a quantitative contrast-noise analysis confirm that images of a hot-rod phantom are practically identical when reconstructed with standard POSEM, DM-DV-POSEM or DM-DV-SROSEM. However, compared to POSEM, DM-DV-POSEM can reach the same contrast 5.0 times faster, while with DM-DV-SROSEM this acceleration factor increases to 11.5. Furthermore, mouse cardiac and bone images reconstructed with DM-DV-SROSEM are visually almost indistinguishable from POSEM reconstructed images but typically need an order of magnitude less reconstruction time.

Pinhole collimation is widely recognized for offering superior resolution-sensitivity trade-off in SPECT imaging of small subjects. The newly developed EXIRAD-3D autoradiography technique (MILabs B.V.) based on a highly focusing multi-pinhole collimator achieves micron-resolution SPECT for cryo-cooled tissue samples. For such high resolutions, the choice of pinhole material may have a significant impact on images. Therefore, this paper aims to compare the performance of EXIRAD-3D with lead, tungsten, gold, and depleted uranium pinhole collimators designed such that they achieve equal sensitivities. Performance in terms of resolution is characterized for several radioisotopes, namely 111In (171 keV and 245 keV), 99mTc (140 keV), 201Tl (71 keV), and 125I (27 keV). Using Monte Carlo simulation, point spread functions were generated and their profiles as well as their full-width-at-half-maximum and full-width-at-tenth-maximum were determined and evaluated for different materials and isotopes. Additionally, simulated reconstructions of a Derenzo resolution phantom, validated with experimental data, were judged by assessment of the resolvable rods as well as a contrast-to-noise ratio (CNR) analysis. Our results indicate that using materials with higher photon-stopping power yields images with better CNR for the studied isotopes with improvements ranging from 1.9% to 36.6%. Visual assessment on the reconstructed images suggests that for EXIRAD-3D, the tungsten collimator is generally a good choice for a wide range of SPECT isotopes. For relatively high-energy isotopes such as 111In, using gold inserts can be beneficial.

In clinical brain SPECT, correction for photon attenuation in the patient is essential to obtain images which provide quantitative information on the regional activity concentration per unit volume (kBq. ml − 1 ). This correction generally requires an attenuation map ( μ map) denoting the attenuation coefficient at each voxel which is often derived from a CT or MRI scan. However, such an additional scan is not always available and the method may suffer from registration errors. Therefore, we propose a SPECT-only-based strategy for μ map estimation that we apply to a stationary multi-pinhole clinical SPECT system (G-SPECT-I) for 99mTc-HMPAO brain perfusion imaging. The method is based on the use of a convolutional neural network (CNN) and was validated with Monte Carlo simulated scans. Data acquired in list mode was used to employ the energy information of both primary and scattered photons to obtain information about the tissue attenuation as much as possible. Multiple SPECT reconstructions were performed from different energy windows over a large energy range. Locally extracted 4D SPECT patches (three spatial plus one energy dimension) were used as input for the CNN which was trained to predict the attenuation coefficient of the corresponding central voxel of the patch. Results show that Attenuation Correction using the Ground Truth μ maps (GT-AC) or using the CNN estimated μ maps (CNN-AC) achieve comparable accuracy. This was confirmed by a visual assessment as well as a quantitative comparison; the mean deviation from the GT-AC when using the CNN-AC is within 1.8% for the standardized uptake values in all brain regions. Therefore, our results indicate that a CNN-based method can be an automatic and accurate tool for SPECT attenuation correction that is independent of attenuation data from other imaging modalities or human interpretations about head contours.

Planar molecular breast imaging (MBI) is rapidly gaining in popularity in diagnostic oncology. To add 3D capabilities, we introduce a novel molecular breast tomosynthesis (MBT) scanner concept based on multi-pinhole collimation. In our design, the patient lies prone with the pendant breast lightly compressed between transparent plates. Integrated webcams view the breast through these plates and allow the operator to designate the scan volume (e.g. a whole breast or a suspected region). The breast is then scanned by translating focusing multi-pinhole plates and NaI(Tl) gamma detectors together in a sequence that optimizes count yield from the volume-of-interest. With simulations, we compared MBT with existing planar MBI. In a breast phantom containing different lesions, MBT improved tumour-to-background contrast-to-noise ratio (CNR) over planar MBI by 12% and 111% for 4.0 and 6.0 mm lesions respectively in case of whole breast scanning. For the same lesions, much larger CNR improvements of 92% and 241% over planar MBI were found in a scan that focused on a breast region containing several lesions. MBT resolved 3.0 mm rods in a Derenzo resolution phantom in the transverse plane compared to 2.5 mm rods distinguished by planar MBI. While planar MBI cannot provide depth information, MBT offered 4.0 mm depth resolution. Our simulations indicate that besides offering 3D localization of increased tracer uptake, multi-pinhole MBT can significantly increase tumour-to-background CNR compared to planar MBI. These properties could be promising for better estimating the position, extend and shape of lesions and distinguishing between single and multiple lesions.

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.

In recent years, breast imaging using radiolabelled molecules has attracted significant interest. Our group has proposed a multi-pinhole molecular breast tomosynthesis (MP-MBT) scanner to obtain 3D functional molecular breast images at high resolutions. After conducting extensive optimisation studies using simulations, we here present a first prototype of MP-MBT and evaluate its performance using physical phantoms. The MP-MBT design is based on two opposing gamma cameras that can image a lightly compressed pendant breast. Each gamma camera consists of a 250 × 150 mm2 detector equipped with a collimator with multiple pinholes focusing on a line. The NaI(Tl) gamma detector is a customised design with 3.5 mm intrinsic spatial resolution and high spatial linearity near the edges due to a novel light-guide geometry and the use of square PMTs. A volume-of-interest is scanned by translating the collimator and gamma detector together in a sequence that optimises count yield from the scan region. Derenzo phantom images showed that the system can reach 3.5 mm resolution for a clinically realistic 99mTc activity concentration in an 11-minute scan, while in breast phantoms the smallest spheres visible were 6 mm in diameter for the same scan time. To conclude, the experimental results of the novel MP-MBT scanner showed that the setup had sub-centimetre breast tumour detection capability which might facilitate 3D molecular breast cancer imaging in the future.

SPECT can be used to image dopamine transporter (DaT) availability in the human striatum, e.g. for diagnosis of Parkinson's disease (PD). As traditional SPECT provides limited resolution and sensitivity, we proposed a full ring focusing multi-pinhole SPECT system (G-SPECT-I (Beekman 2015 Eur. J. Nucl. Med. Mol. Imaging 42 S209)) which demonstrated a 2.5 mm reconstructed resolution in phantom scans. G-SPECT-I achieves data completeness in the scan region of interest by translating the patient bed with an xyz-stage and combining projections from all bed positions into image reconstruction using a scanning focus method (SFM). This paper aims to develop dedicated SFM parameters for performing a DaTscan with high effective sensitivity and appropriate sampling. To this end, the axial scanning length was restricted and transaxial bed trajectories with a reduced number of positions based on a convex hull data-completeness model were tested. Quantitative accuracy was assessed using full G-SPECT-I simulations of an Alderson phantom based on measured system matrices. For each sampling strategy, the specific binding ratio (SBR) and asymmetry index (AI) in the left and right striatum, as well as the Localized SBR (L-SBR) and the Localized AI (L-AI) in eight striatal sub-regions were calculated and compared to those of the reference scan which performs full brain oversampling using 112 bed positions. Results show that structures essential for PD diagnosis were visually and quantitatively barely affected even when using the lowest number of bed translations (i.e. 4). The maximum deviation from the reference was only 1.5%, 1.5%, 5.5% and 7.0% for the SBR, AI, L-SBR and L-AI, respectively, when 4 positions were used. Thus, it is possible to perform an accurate DaTscan with a confined axial scan region and a limited number of focused bed positions. This enables protocols for extremely fast dynamic SPECT scans with less than half-minute time frames, which can be useful for motion correction.

Scintillation gamma cameras based on low-noise electron multiplication (EM-)CCDs can reach high spatial resolutions. For further improvement of these gamma cameras, more insight is needed into how various parameters that characterize these devices influence their performance. Here, we use the Cramer-Rao lower bound (CRLB) to investigate the sensitivity of the energy and spatial resolution of an EM-CCD-based gamma camera to several parameters. The gamma camera setup consists of a 3 mm thick CsI(Tl) scintillator optically coupled by a fiber optic plate to the E2V CCD97 EM-CCD. For this setup, the position and energy of incoming gamma photons are determined with a maximum-likelihood detection algorithm. To serve as the basis for the CRLB calculations, accurate models for the depth-dependent scintillation light distribution are derived and combined with a previously validated statistical response model for the EM-CCD. The sensitivity of the lower bounds for energy and spatial resolution to the EM gain and the depth-of-interaction (DOI) are calculated and compared to experimentally obtained values. Furthermore, calculations of the influence of the number of detected optical photons and noise sources in the image area on the energy and spatial resolution are presented. Trends predicted by CRLB calculations agree with experiments, although experimental values for spatial and energy resolution are typically a factor of 1.5 above the calculated lower bounds. Calculations and experiments both show that an intermediate EM gain setting results in the best possible spatial or energy resolution and that the spatial resolution of the gamma camera degrades rapidly as a function of the DOI. Furthermore, calculations suggest that a large improvement in gamma camera performance is achieved by an increase in the number of detected photons or a reduction of noise in the image area. A large noise reduction, as is possible with a new generation of EM-CCD electronics, may improve the energy and spatial resolution by a factor of 1.5.

The recently developed versatile emission computed tomography (VECTor) technology enables high-energy SPECT and simultaneous SPECT and PET of small animals at sub-mm resolutions. VECTor uses dedicated clustered pinhole collimators mounted in a scanner with three stationary large-area NaI(Tl) gamma detectors. Here, we develop and validate dedicated image reconstruction methods that compensate for image degradation by incorporating accurate models for the transport of high-energy annihilation gamma photons. Ray tracing software was used to calculate photon transport through the collimator structures and into the gamma detector. Input to this code are several geometric parameters estimated from system calibration with a scanning 99mTc point source. Effects on reconstructed images of (i) modelling variable depth-of-interaction (DOI) in the detector, (ii) incorporating photon paths that go through multiple pinholes ('multiple-pinhole paths' (MPP)), and (iii) including various amounts of point spread function (PSF) tail were evaluated. Imaging 18F in resolution and uniformity phantoms showed that including large parts of PSFs is essential to obtain good contrast-noise characteristics and that DOI modelling is highly effective in removing deformations of small structures, together leading to 0.75 mm resolution PET images of a hot-rod Derenzo phantom. Moreover, MPP modelling reduced the level of background noise. These improvements were also clearly visible in mouse images. Performance of VECTor can thus be significantly improved by accurately modelling annihilation gamma photon transport.

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.

Detection of x-rays and gamma rays with high spatial resolution can be achieved with scintillators that are optically coupled to electron-multiplying charge-coupled devices (EMCCDs). These can be operated at typical frame rates of 50 Hz with low noise. In such a set-up, scintillation light within each frame is integrated after which the frame is analyzed for the presence of scintillation events. This method allows for the use of scintillator materials with relatively long decay times of a few milliseconds, not previously considered for use in photon-counting gamma cameras, opening up an unexplored range of dense scintillators. In this paper, we test CdWO₄ and transparent polycrystalline ceramics of Lu₂O₃:Eu and (Gd,Lu)₂O₃:Eu as alternatives to currently used CsI:Tl in order to improve the performance of EMCCD-based gamma cameras. The tested scintillators were selected for their significantly larger cross-sections at 140 keV ((99m)Tc) compared to CsI:Tl combined with moderate to good light yield. A performance comparison based on gamma camera spatial and energy resolution was done with all tested scintillators having equal (66%) interaction probability at 140 keV. CdWO₄, Lu₂O₃:Eu and (Gd,Lu)₂O₃:Eu all result in a significantly improved spatial resolution over CsI:Tl, albeit at the cost of reduced energy resolution. Lu₂O₃:Eu transparent ceramic gives the best spatial resolution: 65 µm full-width-at-half-maximum (FWHM) compared to 147 µm FWHM for CsI:Tl. In conclusion, these 'slow' dense scintillators open up new possibilities for improving the spatial resolution of EMCCD-based scintillation cameras.

Ultra-high-resolution SPECT images can be obtained with focused multipinhole collimators. Here we investigate the influence of unwanted high tracer uptake outside the scan volume on reconstructed tracer distributions inside the scan volume, for (99m)Tc-tetrofosmin myocardial perfusion scanning in mice. Simulated projections of a digital mouse phantom (MOBY) in a focusing multipinhole SPECT system (U-SPECT-II, MILabs, The Netherlands) were generated. With this system differently sized user-defined scan volumes can be selected, by translating the animal in 3D through the focusing collimators. Scan volume selections were set to (i) a minimal volume containing just the heart, acquired without translating the animal during scanning, (ii) a slightly larger scan volume as is typically applied for the heart, requiring only small XYZ translations during scanning, (iii) same as (ii), but extended further transaxially, and (iv) same as (ii), but extended transaxially to cover the full thorax width (gold standard). Despite an overall negative bias that is significant for the minimal scan volume, all selected volumes resulted in visually similar images. Quantitative differences in the reconstructed myocardium between gold standard and the results from the smaller scan volume selections were small; the 17 standardized myocardial segments of a bull's eye plot, normalized to the myocardial mean of the gold standard, deviated on average 6.0%, 2.5% and 1.9% for respectively the minimal, the typical and the extended scan volume, while maximum absolute deviations were respectively 18.6%, 9.0% and 5.2%. Averaged over ten low-count noisy simulations, the mean absolute deviations were respectively 7.9%, 3.2% and 1.9%. In low-count noisy simulations, the mean and maximum absolute deviations for the minimal scan volume could be reduced to respectively 4.2% and 12.5% by performing a short survey scan of the exterior activity and focusing the remaining scan time at the organ of interest. We conclude that reconstructed tracer distribution in the myocardium can be influenced by activity in surrounding organs when a too narrow scan volume is used. With slightly larger scan volumes this problem is adequately suppressed. This approach produced a smaller mean deviation and may be more effective than employing a narrow scan volume with an additional survey scan.

Gamma cameras based on charge-coupled devices (CCDs) coupled to continuous scintillation crystals can combine a good detection efficiency with high spatial resolutions with the aid of advanced scintillation detection algorithms. A previously developed analytical multi-scale algorithm (MSA) models the depth-dependent light distribution but does not take statistics into account. Here we present and validate a novel statistical maximum-likelihood algorithm (MLA) that combines a realistic light distribution model with an experimentally validated statistical model. The MLA was tested for an electron multiplying CCD optically coupled to CsI(Tl) scintillators of different thicknesses. For (99m)Tc imaging, the spatial resolution (for perpendicular and oblique incidence), energy resolution and signal-to-background counts ratio (SBR) obtained with the MLA were compared with those of the MSA. Compared to the MSA, the MLA improves the energy resolution by more than a factor of 1.6 and the SBR is enhanced by more than a factor of 1.3. For oblique incidence (approximately 45°), the depth-of-interaction corrected spatial resolution is improved by a factor of at least 1.1, while for perpendicular incidence the MLA resolution does not consistently differ significantly from the MSA result for all tested scintillator thicknesses. For the thickest scintillator (3 mm, interaction probability 66% at 141 keV) a spatial resolution (perpendicular incidence) of 147 µm full width at half maximum (FWHM) was obtained with an energy resolution of 35.2% FWHM. These results of the MLA were achieved without prior calibration of scintillations as is needed for many statistical scintillation detection algorithms. We conclude that the MLA significantly improves the gamma camera performance compared to the MSA.

Several new methods for determining the depth of interaction (DOI) of annihilation photons in monolithic scintillator detectors with single-sided, multi-pixel readout are investigated. The aim is to develop a DOI decoding method that allows for practical implementation in a positron emission tomography system. Specifically, calibration data, obtained with perpendicularly incident gamma photons only, are being used. Furthermore, neither detector modifications nor a priori knowledge of the light transport and/or signal variances is required. For this purpose, a clustering approach is utilized in combination with different parameters correlated with the DOI, such as the degree of similarity to a set of reference light distributions, the measured intensity on the sensor pixel(s) closest to the interaction position and the peak intensity of the measured light distribution. The proposed methods were tested experimentally on a detector comprised of a 20 mm x 20 mm x 12 mm polished LYSO: Ce crystal coupled to a 4 x 4 multi-anode photomultiplier. The method based on the linearly interpolated measured intensities on the sensor pixels closest to the estimated (x, y)-coordinate outperformed the other methods, yielding DOI resolutions between similar to 1 and similar to 4.5 mm FWHM depending on the DOI, the (x, y) resolution and the amount of reference data used.

Pinhole SPECT often provides an excellent resolution sensitivity trade-off for radionuclide imaging compared to SPECT with parallel holes, particularly when imaging small experimental animals like rodents. High absorption pinhole materials are often chosen because of their low edge penetration and therefore good system resolution. Capturing more photons in the edges however results in decreased system sensitivity if the pinhole diameter remains the same, which may partly undo the beneficial effect on the resolution. In the search for an optimal trade-off we have compared pinhole projection data and reconstructed images of different materials with pinhole aperture diameters adjusted to obtain equal sensitivity. Monte Carlo calculations modeling the transmission, penetration and scattering of gamma radiation in single pinholes of uranium, gold, tungsten and lead were performed for a range of pinhole opening angles, diameters and gamma ray energies. In addition, reconstructed images of a hot rod phantom were determined for a multipinhole SPECT system and for a system that can image the 511 keV annihilation photons of positron emitting tracers with clustered pinholes. Our results indicate that, under the condition of equal sensitivity, tungsten and for SPECT also lead pinholes perform just as well as gold and uranium ones, indicating that a significant cost reduction can be achieved in pinhole collimator manufacturing while the use of rare or impractical materials can be avoided.

Block-iterative image reconstruction methods, such as ordered subset expectation maximization (OSEM), are commonly used to accelerate image reconstruction. In OSEM, the speed-up factor over maximum likelihood expectation maximization (MLEM) is approximately equal to the number of subsets in which the projection data are divided. Traditionally, each subset consists of a couple of projection views, and the more subsets are used, the more the solution deviates from MLEM solutions. We found for multi-pinhole single photon emission computed tomography (SPECT) that even moderate acceleration factors in OSEM lead to inaccurate reconstructions. Therefore, we introduce pixel-based ordered subset expectation maximization (POSEM), which is based on an alternative subset choice. Pixels in each subset are spread out regularly over projections and are spatially separated as much as possible. We validated POSEM for data acquired with a focusing multi-pinhole SPECT system. Performance was compared with traditional OSEM and MLEM for a rat total body bone scan, a gated mouse myocardial perfusion scan and a Defrise phantom scan. We found that POSEM can be operated at acceleration factors that are often an order of magnitude higher than in traditional OSEM.

Item does not contain fulltext Much research is being conducted on position-sensitive scintillation detectors for medical imaging, particularly for emission tomography. Monte Carlo simulations play an essential role in many of these research activities. As the scintillation process, the transport of scintillation photons through the crystal(s), and the conversion of these photons into electronic signals each have a major influence on the detector performance; all of these processes may need to be incorporated in the model to obtain accurate results. In this work the optical and scintillation models of the GEANT4 simulation toolkit are validated by comparing simulations and measurements on monolithic scintillator detectors for high-resolution positron emission tomography (PET). We have furthermore made the GEANT4 optical models available within the user-friendly GATE simulation platform (as of version 3.0). It is shown how the necessary optical input parameters can be determined with sufficient accuracy. The results show that the optical physics models of GATE/GEANT4 enable accurate prediction of the spatial and energy resolution of monolithic scintillator PET detectors.

Gamma cameras based on charge-coupled devices (CCDs) and micro-columnar CsI scintillators can reach high spatial resolutions. However, the gamma interaction probability of these scintillators is low (typically30% at 141 keV) due to the limited thickness of presently available micro-columnar scintillators. Continuous scintillators can improve the interaction probability but suffer from increased light spread compared to columnar scintillators. In addition, for both types of scintillators, gamma photons incident at an oblique angle reduce the spatial resolution due to the variable depth of interaction (DOI). To improve the spatial resolution and spectral characteristics of these detectors, we have developed a fast analytic scintillation detection algorithm that makes use of a depth-dependent light spread model and as a result is able to estimate the DOI in the scintillator. This algorithm, performing multi-scale frame analysis, was tested for an electron multiplying CCD (EM-CCD) optically coupled to CsI(Tl) scintillators of different thicknesses. For the thickest scintillator (2.6 mm) a spatial resolution of 148 microm full width half maximum (FWHM) was obtained with an energy resolution of 46% FWHM for perpendicularly incident gamma photons (interaction probability 61% at 141 keV). The multi-scale algorithm improves the spatial resolution up to 11%, the energy resolution up to 36% and the signal-to-background counts ratio up to 46% compared to a previously implemented algorithm that did not model the depth-dependent light spread. In addition, the multi-scale algorithm can accurately estimate DOI. As a result, degradation of the spatial resolution due to the variable DOI for gamma photons incident at a 45 degrees angle was improved from 2.0 10(3) to 448 microm FWHM. We conclude that the multi-scale algorithm significantly improves CCD-based gamma cameras as can be applied in future SPECT systems.

Charge-coupled devices (CCDs) coupled to scintillation crystals can be used for high-resolution imaging with x-rays and gamma rays. When the CCD images can be read out fast enough, the energy and interaction position of individual gamma quanta can be estimated by a real-time image analysis of the scintillation light flashes ('photon-counting mode'). The electron-multiplying CCD (EMCCD) is well suited for fast read out, since even at high frame rates it has extremely low read-out noise. Back-illuminated (BI) EMCCDs have much higher quantum efficiency than front-illuminated (FI) EMCCDs. Here we compare the spatial and energy resolution of gamma cameras based on FI and BI EMCCDs. The CCDs are coupled to a 1000 microm thick columnar CsI(Tl) crystal for the purpose of Tc-99m and I-125 imaging. Intrinsic spatial resolutions of 44 microm for I-125 and 49 microm for Tc-99m were obtained when using a BI EMCCD, which is an improvement by a factor of about 1.2-2 over the FI EMCCD. Furthermore, in the energy spectrum of the BI EMCCD, the I-125 signal could be clearly separated from the background noise, which was not the case for the FI EMCCD. The energy resolution of a BI EMCCD for Tc-99m was estimated to be approximately 36 keV, full width at half maximum, at 141 keV. The excellent results for the BI EMCCD encouraged us to investigate the cooling requirements for our setup. We have found that for the BI EMCCD, the spatial and energy resolution, as well as image noise, remained stable over a range of temperatures from -50 degrees C to -15 degrees C. This is a significant advantage over the FI EMCCD, which suffered from loss of spatial and especially energy resolution at temperatures as low as -40 degrees C. We conclude that the use of BI EMCCDs may significantly improve the imaging capabilities and the cost efficiency of CCD-based high-resolution gamma cameras.

Single photon emission computed tomography (SPECT) images are degraded by the detection of scattered photons and photons that penetrate the collimator septa. In this paper, a previously proposed Monte Carlo software that employs fast object scatter simulation using convolution-based forced detection (CFD) is extended towards a wide range of medium and high energy isotopes measured using various collimators. To this end, a fast method was developed for incorporating effects of septal penetrating (SP) photons. The SP contributions are obtained by calculating the object attenuation along the path from primary emission to detection followed by sampling a pre-simulated and scalable septal penetration point spread function (SP-PSF). We found that with only a very slight reduction in accuracy, we could accelerate the SP simulation by four orders of magnitude. To achieve this, we combined: (i) coarse sampling of the activity and attenuation distribution; (ii) simulation of the penetration only for a coarse grid of detector pixels followed by interpolation and (iii) neglection of SP-PSF elements below a certain threshold. By inclusion of this SP-PSF-based simulation it became possible to model both primary and septal penetrated photons while only 10% extra computation time was added to the CFD-based Monte Carlo simulator. As a result, a SPECT simulation of a patient-like distribution including SP now takes less than 5 s per projection angle on a dual processor PC. Therefore, the simulator is well-suited as an efficient projector for fully 3D model-based reconstruction or as a fast data-set generator for applications such as image processing optimization or observer studies.

X-ray CT images obtained with iterative reconstruction (IR) can be hampered by the so-called edge and aliasing artefacts, which appear as interference patterns and severe overshoots in the areas of sharp intensity transitions. Previously, we have demonstrated that these artefacts are caused by discretization errors during the projection simulation step in IR. Although these errors are inherent to IR, they can be adequately suppressed by reconstruction on an image grid that is finer than that typically used for analytical methods such as filtered back-projection. Two other methods that may prevent edge artefacts are: (i) smoothing the projections prior to reconstruction or (ii) using an image representation different from voxels; spherically symmetric Kaiser-Bessel functions are a frequently employed example of such a representation. In this paper, we compare reconstruction on a fine grid with the two above-mentioned alternative strategies for edge artefact reduction. We show that the use of a fine grid results in a more adequate suppression of artefacts than the smoothing of projections or using the Kaiser-Bessel image representation.

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.

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.

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.

Quantitative accuracy of single photon emission computed tomography (SPECT) images is highly dependent on the photon scatter model used for image reconstruction. Monte Carlo simulation (MCS) is the most general method for detailed modeling of scatter, but to date, fully three-dimensional (3-D) MCS-based statistical SPECT reconstruction approaches have not been realized, due to prohibitively long computation times and excessive computer memory requirements. MCS-based reconstruction has previously been restricted to two-dimensional approaches that are vastly inferior to fully 3-D reconstruction. Instead of MCS, scatter calculations based on simplified but less accurate models are sometimes incorporated in fully 3-D SPECT reconstruction algorithms. We developed a computationally efficient fully 3-D MCS-based reconstruction architecture by combining the following methods: 1) a dual matrix ordered subset (DM-OS) reconstruction algorithm to accelerate the reconstruction and avoid massive transition matrix precalculation and storage; 2) a stochastic photon transport calculation in MCS is combined with an analytic detector modeling step to reduce noise in the Monte Carlo (MC)-based reprojection after only a small number of photon histories have been tracked; and 3) the number of photon histories simulated is reduced by an order of magnitude in early iterations, or photon histories calculated in an early iteration are reused. For a 64/spl times/64/spl times/64 image array, the reconstruction time required for ten DM-OS iterations is approximately 30 min on a dual processor (AMD 1.4 GHz) PC, in which case the stochastic nature of MCS modeling is found to have a negligible effect on noise in reconstructions. Since MCS can calculate photon transport for any clinically used photon energy and patient attenuation distribution, the proposed methodology is expected to be useful for obtaining highly accurate quantitative SPECT images within clinically acceptable computation times.

Pinhole collimation can provide both higher sensitivity and resolution than parallel hole collimation when used to image small objects. When objects are placed close to the pinhole, small pinhole diameters combined with high-magnification pinhole geometries yield ultra high resolution images. With Monte Carlo (MC) calculations it is possible to simulate accurately a wide range of features of pinhole imaging. The aim of the present work is to accelerate MC simulations of pinhole SPECT projections. To achieve speed-up, forced detection (FD), a commonly used acceleration technique, is replaced by a kernel-based forced detection (KFD) step. In KFD, instead of tracing individual photons from the source or last scatter position to the detector, a position dependent kernel (point spread function (PSF)) is projected on the detector. The PSFs for channel and knife edge pinhole apertures model the penetration effects through the aperture material. For simulations, the PSFs are pre-calculated and stored in tables. The speed-up and accuracy achieved by using KFD were validated by means of digital phantoms. MC simulations with FD and with KFD converge to almost identical images. However, KFD converges to an equal image noise level one to four orders of magnitude faster than FD, depending on the number of photons simulated. A simulator accelerated by KFD could serve as a practical tool to improve iterative image reconstruction.

Imaging of Tc-99m labelled tracers is gaining popularity for detecting breast tumours. Recently, we proposed a novel design for molecular breast tomosynthesis (MBT) based on two sliding focusing multi-pinhole collimators that scan a modestly compressed breast. Simulation studies indicate that MBT has the potential to improve the tumour-to-background contrast-to-noise ratio significantly over state-of-the-art planar molecular breast imaging. The aim of the present paper is to optimize the collimator-detector geometry of MBT. Using analytical models, we first optimized sensitivity at different fixed system resolutions (ranging from 5 to 12 mm) by tuning the pinhole diameters and the distance between breast and detector for a whole series of automatically generated multi-pinhole designs. We evaluated both MBT with a conventional continuous crystal detector with 3.2 mm intrinsic resolution and with a pixelated detector with 1.6 mm pixels. Subsequently, full system simulations of a breast phantom containing several lesions were performed for the optimized geometry at each system resolution for both types of detector. From these simulations, we found that tumour-to-background contrast-to-noise ratio was highest for systems in the 7 mm to 10 mm system resolution range over which it hardly varied. No significant differences between the two detector types were found.

Statistical methods for image reconstruction such as the maximum likelihood expectation maximization are more robust and flexible than analytical inversion methods and allow for accurate modelling of the counting statistics and photon transport during acquisition of projection data. Statistical reconstruction is prohibitively slow when applied to clinical x-ray CT due to the large data sets and the high number of iterations required for reconstructing high-resolution images. Recently, however, powerful methods for accelerating statistical reconstruction have been proposed which, instead of accessing all projections simultaneously for updating an image estimate, are based on accessing a subset of projections at the time during iterative reconstruction. In this paper we study images generated by the convex algorithm accelerated by the use of ordered subsets (the OS convex algorithm (OSC)) for data sets with sizes, noise levels and spatial resolution representative of x-ray CT imaging. It is only in the case of extremely high acceleration factors (higher than 50, corresponding to fewer than 20 projections per subset), that areas with incorrect grey values appear in the reconstructed images, and that image noise increases compared with the standard convex algorithm. These image degradations can be adequately corrected for by running the final iteration of OSC with a reduced number of subsets. Even by applying such a relatively slow final iteration, OSC produces almost an equal resolution and lesion contrast as the standard convex algorithm, but more than two orders of magnitude faster.

Accurate simulation of scatter in projection data of single photon emission computed tomography (SPECT) is computationally extremely demanding for activity distribution in non-uniform dense media. This paper suggests how the computation time and memory requirements can be significantly reduced. First the scatter projection of a uniform dense object (P(SDSE)) is calculated using a previously developed accurate and fast method which includes all orders of scatter (slab-derived scatter estimation), and then P(SDSE) is transformed towards the desired projection P which is based on the non-uniform object. The transform of P(SDSE) is based on two first-order Compton scatter Monte Carlo (MC) simulated projections. One is based on the uniform object (P(u)) and the other on the object with non-uniformities (P(nu)). P is estimated by P = P(SDSE) P(nu)/P(u). A tremendous decrease in noise in P is achieved by tracking photon paths for P(nu) identical to those which were tracked for the calculation of P(u) and by using analytical rather than stochastic modelling of the collimator. The method was validated by comparing the results with standard MC-simulated scatter projections (P) of 99mTc and 201Tl point sources in a digital thorax phantom. After correction, excellent agreement was obtained between P and P. The total computation time required to calculate an accurate scatter projection of an extended distribution in a thorax phantom on a PC is a only few tens of seconds per projection, which makes the method attractive for application in accurate scatter correction in clinical SPECT. Furthermore, the method removes the need of excessive computer memory involved with previously proposed 3D model-based scatter correction methods.

SPECT projections are contaminated by scatter, resulting in reduced image contrast and quantitative errors. When tissue is present behind the source, some of the detected photons backscatter via this tissue. Particularly in dual-isotope SPECT and in combined emission-transmission SPECT, backscatter constitutes a major part of the down-scatter contamination in lower-energy windows. In this paper, the effects of backscatter material were investigated. Planar images of 99mTc and 201Tl line sources between varying numbers of Perspex slabs were analysed using the photopeak windows and various scatter windows. In the 99mTc photopeak window no significant change in total counts due to backscatter material was measured. In the 201Tl photopeak window an increase of about 10% in total counts was observed. In the scatter windows an even more explicit influence of backscatter material was measured. For instance, at a forward depth of 10 cm, total counts of a 99mTc source detected in the 72 keV window eventually doubled with increasing backscatter material, compared with the situation without backscatter material. The backscatter contribution plateaued when more than 5-10 cm of scatter material was placed behind the source. In conclusion, backscatter should be taken into account, particularly in model-based down-scatter correction methods in dual-isotope SPECT and combined emission-transmission SPECT.

Iterative reconstruction from single photon emission computed tomography (SPECT) data requires regularization to avoid noise amplification and edge artefacts in the reconstructed image. This is often accomplished by stopping the iteration process at a relatively low number of iterations or by post-filtering the reconstructed image. The aim of this paper is to develop a method to automatically select an optimal combination of stopping iteration number and filters for a particular imaging situation. To this end different error measures between the distribution of a phantom and a corresponding filtered SPECT image are minimized for different iteration numbers. As a study example, simulated data representing a brain study are used. For post-reconstruction filtering, the performance of 3D linear diffusion (Gaussian filtering) and edge preserving 3D nonlinear diffusion (Catté scheme) is investigated. For reconstruction methods which model the image formation process accurately, error measures between the phantom and the filtered reconstruction are significantly reduced by performing a high number of iterations followed by optimal filtering compared with stopping the iterative process early. Furthermore, this error reduction can be obtained over a wide range of iteration numbers. Only a negligibly small additional reduction of the errors is obtained by including spatial variance in the filter kernel. Compared with Gaussian filtering, Catté diffusion can further reduce the error in some cases. For the examples considered, using accurate image formation models during iterative reconstruction is far more important than the choice of the filter.

Effects of different scatter compensation methods incorporated in fully 3D iterative reconstruction are investigated. The methods are: (i) the inclusion of an 'ideal scatter estimate' (ISE); (ii) like (i) but with a noiseless scatter estimate (ISE-NF); (iii) incorporation of scatter in the point spread function during iterative reconstruction ('ideal scatter model', ISM); (iv) no scatter compensation (NSC); (v) ideal scatter rejection (ISR), as can be approximated by using a camera with a perfect energy resolution. The iterative method used was an ordered subset expectation maximization (OS-EM) algorithm. A cylinder containing small cold spheres was used to calculate contrast-to-noise curves. For a brain study, global errors between reconstruction and 'true' distributions were calculated. Results show that ISR is superior to all other methods. In all cases considered, ISM is superior to ISE and performs approximately as well as (brain study) or better than (cylinder data) ISE-NF. Both ISM and ISE improve contrast-to-noise curves and reduce global errors, compared with NSC. In the case of ISE, blurring of the scatter estimate with a Gaussian kernel results in slightly reduced errors in brain studies, especially at low count levels. The optimal Gaussian kernel size is strongly dependent on the noise level.

Ordered subsets expectation maximization (OSEM) is widely used to accelerate tomographic reconstruction. Speed-up of OSEM over maximum likelihood expectation maximization (MLEM) is close to the number of subsets (NS). Recently we significantly increased the speed-up achievable with OSEM by specific subset choice (pixel-based OSEM). However, a high NS can cause undesirable noise levels, quantitative inaccuracy or even disappearance of lesions in low-activity image regions, while a low NS leads to prohibitively long reconstructions or unrecovered details in highly active regions. Here, we introduce count-regulated OSEM (CROSEM) which locally adapts the effective NS based on the estimated amount of detected photons originating from individual voxels. CROSEM was tested using multi-pinhole SPECT simulations and in vivo imaging. With the maximum NS set to 128, CROSEM attained acceleration factors close to 128 in high-activity regions and kept quantitative accuracy in low-activity regions close to that of MLEM. At equal cold-lesion contrast in high-activity regions, CROSEM exhibited lower noise than MLEM in low-activity regions. CROSEM is a fast and stable alternative to OSEM, preventing excessive image noise and quantitative errors in low-activity regions while achieving high-resolution recovery in structures with high activity uptake.

There is an increasing interest in iterative reconstruction (IR) as a key tool to improve quality and increase applicability of x-ray CT imaging. IR has the ability to significantly reduce patient dose; it provides the flexibility to reconstruct images from arbitrary x-ray system geometries and allows one to include detailed models of photon transport and detection physics to accurately correct for a wide variety of image degrading effects. This paper reviews discretization issues and modelling of finite spatial resolution, Compton scatter in the scanned object, data noise and the energy spectrum. The widespread implementation of IR with a highly accurate model-based correction, however, still requires significant effort. In addition, new hardware will provide new opportunities and challenges to improve CT with new modelling. ispartof: Physics in Medicine and Biology vol:58 issue:12 pages:R63-R96 ispartof: location:England status: published

The quality and quantitative accuracy of iteratively reconstructed SPECT images improves when better point spread function (PSF) models of the gamma camera are used during reconstruction. Here, inclusion in the PSF model of photon crosstalk between different slices caused by limited gamma camera resolution and scatter is examined. A three-dimensional (3-D) projector back-projector (proback) has been developed which models both the distance dependent detector point spread function and the object shape-dependent scatter point spread function of single photon emission computed tomography (SPECT). A table occupying only a few megabytes of memory is sufficient to represent this scatter model. The contents of this table are obtained by evaluating an analytical expression for object shape-dependent scatter. The proposed approach avoids the huge memory requirements of storing the full transition matrix needed for 3-D reconstruction including object shape-dependent scatter. In addition, the method avoids the need for lengthy Monte Carlo simulations to generate such a matrix. In order to assess the quantitative accuracy of the method, reconstructions of a water filled cylinder containing regions of different activity levels and of simulated 3-D brain projection data have been evaluated for technetium-99m. It is shown that fully 3-D reconstruction including complete detector response and object shape-dependent scatter modeling clearly outperforms simpler methods that lack a complete detector response and/or a complete scatter response model. Fully 3-D scatter correction yields the best quantitation of volumes of interest and the best contrast-to-noise curves.

A fast simulator of SPECT projection data taking into account attenuation, distance dependent detector response, and scatter has been developed, based on an analytical point spread function model. The parameters of the scatter response are obtained from a single line source measurement with a triangular phantom. The simulator is able to include effects of object curvature on the scatter response to a high accuracy. The simulator has been evaluated for homogeneous media by measurements of /sup 99m/Tc point sources placed at different locations in a water-filled cylinder at energy windows of 15% and 20%. The asymmetrical shapes of measured projections of point sources are In excellent agreement with simulations for both energy windows. Scatter-to-primary ratio (SPR) calculations of point sources at different positions in a cylindrical phantom differ not more than a few percent from measurements. The simulator uses just a few megabytes of memory for storing the tables representing the forward model; furthermore, simulation of 60 SPECT projections from a three-dimensional digital brain phantom with 6-mm cubic voxels takes only ten minutes on a standard workstation. Therefore, the simulator could serve as a projector in iterative true 3-D SPECT reconstruction. >

In this paper we report on Monte Carlo simulations to investigate real-time monitoring of the track depth profile in particle therapy by measuring prompt gamma ray emissions: a high sensitivity imaging system employing a knife-edge-shaped slit combined with a position-sensitive gamma detector was evaluated. Calculations to test this new concept were performed for a head-sized software phantom. Clear spatial correlation is shown between the distribution of gamma rays detected with energies above 1.5 MeV and the distribution of prompt gamma rays emitted from the phantom. The number of neutrons originating from nuclear reactions in the phantom that are detected at these high energies is small. Most importantly it is shown that under common therapy conditions enough data may be collected during one spot-step (of the order of 10 ms) to locate the distal dose edge with a 1σ accuracy of better than 1 mm. This indicates that simple slit cameras have high potential for accurate real-time particle therapy adjustment and may become a practical way to improve particle therapy accuracy.

Detection of scattered gamma quanta degrades image contrast and quantitative accuracy of single-photon emission computed tomography (SPECT) imaging. This paper reviews methods to characterize and model scatter in SPECT and correct for its image degrading effects, both for clinical and small animal SPECT. Traditionally scatter correction methods were limited in accuracy, noise properties and/or generality and were not very widely applied. For small animal SPECT, these approximate methods of correction are often sufficient since the fraction of detected scattered photons is small. This contrasts with patient imaging where better accuracy can lead to significant improvement of image quality. As a result, over the last two decades, several new and improved scatter correction methods have been developed, although often at the cost of increased complexity and computation time. In concert with (i) the increasing number of energy windows on modern SPECT systems and (ii) excellent attenuation maps provided in SPECT/CT, some of these methods give new opportunities to remove degrading effects of scatter in both standard and complex situations and therefore are a gateway to highly quantitative single- and multi-tracer molecular imaging with improved noise properties. Widespread implementation of such scatter correction methods, however, still requires significant effort.

We aim to study the effects of activity distribution for multiplexing multi-pinhole (MPH) SPECT. Three digital phantoms, including a hot rod, a cold rod and a cold sphere phantom, were used. Different degrees of multiplexing were obtained by (i) adjusting the MPH pattern for the same 4-pinhole collimator (scheme 1) and (ii) increasing the number of pinholes (scheme 2). Noise-free and noisy projections were generated using a 3D analytical MPH projector based on the same acquisition time. Projections were reconstructed using OS–EM without resolution recovery. Normalized mean-square-error (NMSE), noise, image profiles and signal-to-background ratios (SBR) were assessed. For the hot rod phantom, the NMSE-noise trade-offs slightly improves for multiplexing designs in scheme 2. Substantial artifacts were observed and the NMSE-noise trade-offs slightly worsened for multiplexing designs for the cold phantoms. Resolutions slightly degraded for higher degrees of multiplexing (~39–65%) for the cold rod phantom. For the cold sphere phantom, image profiles showed non-multiplexing designs better emulated the phantom, while ~20% multiplexing performs similarly as compared to non-multiplexing in SBR. Our results indicate that multiplexing can help for sparse objects but leads to a significant image degradation in non-sparse distributions. Since many tracers are not highly specific, and the gain of detection efficiency by allowing multiplexing is fairly offset by image degradations, multiplexing needs to be kept to a minimum for optimum MPH collimator designs.

Item does not contain fulltext 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.

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.

The use of time-of-flight (TOF) information in positron emission tomography (PET) enables significant improvement in image noise properties and, therefore, lesion detection. Silicon photomultipliers (SiPMs) are solid-state photosensors that have several advantages over photomultiplier tubes (PMTs). SiPMs are small, essentially transparent to 511 keV gamma rays and insensitive to magnetic fields. This enables novel detector designs aimed at e.g. compactness, high resolution, depth-of-interaction (DOI) correction and MRI compatibility. The goal of the present work is to study the timing performance of SiPMs in combination with LaBr(3):Ce(5%), a relatively new scintillator with promising characteristics for TOF-PET. Measurements were performed with two, bare, 3 mm x 3 mm x 5 mm LaBr(3):Ce(5%) crystals, each coupled to a 3 mm x 3 mm SiPM. Using a (22)Na point source placed at various positions in between the two detectors, a coincidence resolving time (CRT) of approximately 100 ps FWHM for 511 keV annihilation photon pairs was achieved, corresponding to a TOF positioning resolution of approximately 15 mm FWHM. At the same time, pulse height spectra with well-resolved full-energy peaks were obtained. To our knowledge this is the best CRT reported for SiPM-based scintillation detectors to date. It is concluded that SiPM-based scintillation detectors can provide timing resolutions at least as good as detectors based on PMTs.

State-of-the-art small-animal single photon emission computed tomography (SPECT) enables sub-half-mm resolution imaging of radio-labelled molecules. Due to severe photon penetration through pinhole edges, current multi-pinhole SPECT is not suitable for high-resolution imaging of photons with high energies, such as the annihilation photons emitted by positron emitting tracers (511 keV). To deal with this edge penetration, we introduce here clustered multi-pinhole SPECT (CMP): each pinhole in a cluster has a narrow opening angle to reduce photon penetration. Using simulations, CMP is compared with (i) a collimator with traditional pinholes that is currently used for sub-half-mm imaging of SPECT isotopes (U-SPECT-II), and (ii), like (i) but with collimator thickness adapted to image high-energy photons (traditional multi-pinhole SPECT, TMP). At 511 keV, U-SPECT-II is able to resolve the 0.9 mm rods of an iteratively reconstructed Jaszczak-like capillary hot rod phantom, and while TMP only leads to small improvements, CMP can resolve rods as small as 0.7 mm. Using a digital tumour phantom, we show that CMP resolves many details not assessable with standard USPECT-II and TMP collimators. Furthermore, CMP makes it possible to visualize uptake of positron emitting tracers in sub-compartments of a digital mouse striatal brain phantom. This may open up unique possibilities for analysing processes such as those underlying the function of neurotransmitter systems. Additional potential of CMP may include (i) the imaging of other high-energy single-photon emitters (e.g. I-131) and (ii) localized imaging of positron emitting tracers simultaneously with single photon emitters, with an even better resolution than coincidence PET.

The performance of pinhole single photon emission computed tomography (SPECT) depends on the spatial resolution of the gamma-ray detectors used. Pinhole cameras suffer from strong resolution loss due to the varying depth-of-interaction (DOI) of gamma quanta that enter the detector material at an angle. We eliminate DOI effects in a scintillation gamma camera via a dedicated optic fiber bundle that acts as a focusing collimator for light generated in a scintillation crystal. A curved crystal is connected to a concavely shaped fiber-optic bundle such that the fibers connect perpendicularly to the crystal's convex surface and point straight at the pinhole opening. Limiting the fiber numerical apertures can be used to suppress resolution losses due to light spread. Here we demonstrate experimentally that this prototype position-sensitive gamma sensor successfully eliminates DOI effects, and has an intrinsic resolution of better than 280 microm full width at half maximum with an interaction probability of 67% for 140 keV photons. Therefore, the detector has great potential for increasing the resolution of pinhole SPECT.

High-resolution imaging of x-ray and gamma-ray distributions can be achieved with cameras that use charge coupled devices (CCDs) for detecting scintillation light flashes. The energy and interaction position of individual gamma photons can be determined by rapid processing of CCD images of individual flashes. Here we investigate the improvement of such a gamma camera when a micro-machined retro-reflector is used to increase the light output of a continuous scintillation crystal. At 122 keV we found that retro-reflectors improve the intrinsic energy resolution (full width at half maximum (FWHM)) by 32% (from 50% to 34%) and the signal-to-noise (SNR) ratio by 18%. The spatial resolution (FWHM) was improved by about 4%, allowing us to obtain a resolution of 159 microm. The full width at tenth maximum (FWTM) improvement was 13%. Therefore, this enhancement is a next step towards realizing compact high-resolution devices for imaging gamma emitters.