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.
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