Objective. In PET/CT imaging, CT is used for positron emission tomography (PET) attenuation correction (AC). CT artifacts or misalignment between PET and CT can cause AC artifacts and quantification errors in PET. Simultaneous reconstruction (MLAA) of PET activity (λ-MLAA) and attenuation (μ-MLAA) maps was proposed to solve those issues using the time-of-flight PET raw data only. However, λ-MLAA still suffers from quantification error as compared to reconstruction using the gold-standard CT-based attenuation map (μ-CT). Recently, a deep learning (DL)-based framework was proposed to improve MLAA by predicting μ-DL from λ-MLAA and μ-MLAA using an image domain loss function (IM-loss). However, IM-loss does not directly measure the AC errors according to the PET attenuation physics. Our preliminary studies showed that an additional physics-based loss function can lead to more accurate PET AC. The main objective of this study is to optimize the attenuation map generation framework for clinical full-dose 18F-FDG studies. We also investigate the effectiveness of the optimized network on predicting attenuation maps for synthetic low-dose oncological PET studies. Approach. We optimized the proposed DL framework by applying different preprocessing steps and hyperparameter optimization, including patch size, weights of the loss terms and number of angles in the projection-domain loss term. The optimization was performed based on 100 skull-to-toe 18F-FDG PET/CT scans with minimal misalignment. The optimized framework was further evaluated on 85 clinical full-dose neck-to-thigh 18F-FDG cancer datasets as well as synthetic low-dose studies with only 10% of the full-dose raw data. Main results. Clinical evaluation of tumor quantification as well as physics-based figure-of-merit metric evaluation validated the promising performance of our proposed method. For both full-dose and low-dose studies, the proposed framework achieved <1% error in tumor standardized uptake value measures. Significance. It is of great clinical interest to achieve CT-less PET reconstruction, especially for low-dose PET studies.
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