Cyclic 2.5D Perceptual Loss for Cross-Modal 3D Medical Image Synthesis: T1w MRI to Tau PET
About
Positron emission tomography (PET) provides molecular biomarkers for Alzheimer's disease and related dementias (ADRD) and is increasingly used for diagnosis, staging, and clinical trial enrichment. However, its use is limited by cost, regulatory restrictions, and the invasiveness of radiotracer injection. Although current frameworks emphasize multimodal biomarker assessment, including the amyloid/tau/neurodegeneration (A/T/N) scheme, these barriers constrain access to PET imaging. Cross-modal image synthesis may help address this gap by reconstructing unavailable modalities from routine scans. Because PET is clinically valuable for regional uptake patterns rather than exact voxel-wise intensities, perceptual losses that capture higher-level semantic features are well suited to PET synthesis. Existing 2D, 3D, and 2.5D perceptual losses for 3D synthesis each have limitations, including restricted volumetric context, scarcity of pretrained 3D models, and difficulty balancing optimization across anatomical planes. In this study, we synthesize tau PET from structural MRI by generating 3D pseudo-[18F]flortaucipir standardized uptake value ratio (SUVR) maps from 3D T1-weighted MR images. We propose a cyclic 2.5D perceptual loss that alternates optimization across axial, coronal, and sagittal planes during training to improve volumetric consistency. We also standardize PET SUVRs by scanner manufacturer, reducing inter-manufacturer variability and better preserving high-uptake regions. Using cohorts spanning the ADRD spectrum from the ADNI and the SCAN cohort, we show that the method generalizes across U-Net, UNETR, SwinUNETR, CycleGAN, and Pix2Pix, with strong performance. Notably, it improves agreement between synthesized SUVRs and measured PET in brain regions relevant to Alzheimer-type tau pathology. Code is publicly available at https://github.com/labhai/Cyclic-2.5D-Perceptual-Loss.