Purpose <p>Quantitative analysis of PET images in brain PET/CT relies on MRI-derived regions of interest (ROIs). However, the pairs of PET/CT and MR images are not always available, and their alignment is challenging if their acquisition times differ considerably. To address these problems, this study proposes a deep learning framework for translating CT of PET/CT to synthetic MR images (MR_SYN) and performing automated quantitative regional analysis using MR_SYN-derived segmentation.</p> Methods <p>In this retrospective study, 139 subjects who underwent brain [¹⁸F]FBB PET/CT and T1-weighted MRI were included. A U-Net-like model was trained to translate CT images to MR_SYN; subsequently, a separate model was trained to segment MR_SYN into 95 regions. Regional and composite standardised uptake value ratio (SUVr) was calculated in [¹⁸F]FBB PET images using the acquired ROIs. For evaluation of MR_SYN, quantitative measurements including structural similarity index measure (SSIM) were employed, while for MR_SYN-based segmentation evaluation, Dice similarity coefficient (DSC) was calculated. Wilcoxon signed-rank test was performed for SUVrs computed using MR_SYN and ground-truth MR (MR_GT).</p> Results <p>Compared to MR_GT, the mean SSIM of MR_SYN was 0.974 ± 0.005. The MR_SYN-based segmentation achieved a mean DSC of 0.733 across 95 regions. No statistical significance (<i>P</i> &gt; 0.05) was found for SUVr between the ROIs from MR_SYN and those from MR_GT, excluding the precuneus.</p> Conclusion <p>We demonstrated a deep learning framework for automated regional brain analysis in PET/CT with MR_SYN. Our proposed framework can benefit patients who have difficulties in performing an MRI scan.</p>