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Single photon emission computed tomography (SPECT) can enable the quantification of activity uptake in lesions and at-risk organs in α-particle-emitting radiopharmaceutical therapies (α-RPTs). However, this quantification is challenged by the extremely low detected photon counts, complicated isotope physics, and the image-degrading effects in α-RPT SPECT. Thus, strategies to optimize the SPECT system and protocol designs for the task of regional uptake quantification are much needed. Objectively performing this task-based optimization requires a reliable (accurate and precise) regional uptake quantification method. Conventional reconstruction-based quantification (RBQ) methods have been observed to be erroneous for α-RPT SPECT. Projection-domain quantification methods, which estimate regional uptake directly from SPECT projections, have demonstrated potential in providing reliable regional uptake estimates, but these methods assume constant uptake within the regions, an assumption that may not hold. To address these challenges, we propose Wiener INtegration Projection-Domain Quantification (WIN-PDQ), a Wiener-estimator-based projection-domain quantitative SPECT method. The method accounts for the heterogeneity within the regions of interest while estimating mean uptake. An early-stage evaluation of the method was conducted using 3D Monte Carlo-simulated SPECT of anthropomorphic phantoms with 223Ra uptake and lumpy-model-based intra-regional uptake heterogeneity. In this evaluation with phantoms of varying mean regional uptake and intra-regional uptake heterogeneity, the WIN-PDQ method yielded ensemble unbiased estimates and significantly outperformed both reconstruction-based and previously proposed projection-domain quantification methods in terms of normalized root ensemble mean squared error. In conclusion, based on these preliminary findings, the proposed WIN-PDQ method is showing potential for estimating mean regional uptake in α-RPTs and towards enabling the objective task-based optimization of SPECT system and protocol designs.
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