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.

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 m (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.

Introduction: Autoradiography is an established technique for high-resolution imaging of radiolabelled molecules in biological tissue slices. Unfortunately, creating a 3D image from a set of these 2D images is extremely time-consuming and error-prone. MicroSPECT systems provide such 3D images but have a low resolution. Here we present EXIRAD-3D, a fast automated method as an alternative for 3D autoradiography from coupes based on ultra-high resolution microSPECT technology. Methods: EXIRAD-3D uses a very small bore focusing multi-pinhole collimator mounted in a SPECT system with stationary detectors (U-SPECT/CT, MILabs B.V. The Netherlands) using a sample holder with integrated tissue cooling to avoid activity leaking or tissue deformation during the scan. The system performance was experimentally evaluated using various phantoms and tissue samples of animals in vivo injected with technetium-99m and iodine-123. Results: The reconstructed spatial resolution obtained with a Derenzo hot rod phantom was 120 μm (or 1.7 nl). The voxel values of a syringe phantom image appear to be uniform and scale linearly with activity. Uptake in tiny details of the mouse knee joint, thyroid, and kidney could be clearly visualized. Conclusion: EXIRAD-3D opens up the possibility for fast and quantitative 3D imaging of radiolabelled molecules at a resolution far better than in vivo microSPECT and saves tremendous amounts of work compared to obtaining 3D data from a set of 2D autoradiographs. Advances in knowledge and implications for patient care: EXIRAD-3D offers superior image resolution over microSPECT, and it can be a very efficient alternative for autoradiography in pharmaceutical and biological studies.

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.

Biometrics such as ECG provides a convenient and powerful security tool to verify or identify an individual. However, one important drawback of biometrics is that it is irrevocable. In other words, biometrics cannot be re-used practically once it is compromised. Cancelable biometrics has been investigated to overcome this drawback.

A non-local means (NLM) filter is a weighted average of a large number of non-local pixels with various image intensity values. The NLM filters have been shown to have powerful denoising performance, excellent detail preservation by averaging many noisy pixels, and using appropriate values for the weights, respectively. The NLM weights between two different pixels are determined based on the similarities between two patches that surround these pixels and a smoothing parameter. Another important factor that influences the denoising performance is the self-weight values for the same pixel. The recently introduced local James-Stein type center pixel weight estimation method (LJS) outperforms other existing methods when determining the contribution of the center pixels in the NLM filter. However, the LJS method may result in excessively large self-weight estimates since no upper bound is assumed, and the method uses a relatively large local area for estimating the self-weights, which may lead to a strong bias. In this paper, we investigated these issues in the LJS method, and then propose a novel local self-weight estimation methods using direct bounds (LMM-DB) and reparametrization (LMM-RP) based on the Baranchik's minimax estimator. Both the LMM-DB and LMM-RP methods were evaluated using a wide range of natural images and a clinical MRI image together with the various levels of additive Gaussian noise. Our proposed parameter selection methods yielded an improved bias-variance trade-off, a higher peak signal-to-noise (PSNR) ratio, and fewer visual artifacts when compared with the results of the classical NLM and LJS methods. Our proposed methods also provide a heuristic way to select a suitable global smoothing parameters that can yield PSNR values that are close to the optimal values.