Accurate MRI-free PET Quantification and Reliability Assessment via CT-to-MRI Synthesis and Conformal Prediction

Standardized uptake value ratio (SUVR) quantification of amyloid PET commonly relies on a subject-specific T1-weighted MRI, yet a usable MRI is not always available. We therefore combined CT-to-MRI synthesis with conformal prediction for MRI-free PET quantification with reliability assessment. A slice-consistent Brownian Bridge Diffusion Model was strengthened with multi-dataset training and data-source conditioning to enrich the anatomical prior learned from MRI, and with expanded multi-slice CT context to exploit the through-plane continuity of subject-specific anatomy in CT. Synthetic MRI was used for FreeSurfer-based anatomical parcellation and PET quantification, while deep-ensemble uncertainty was calibrated with conformal prediction to estimate a plausible range for the corresponding real MRI-based SUVR. On ^11C-PiB PET from OASIS-3, the proposed method achieved the highest synthesis and parcellation fidelity among the compared methods. Mean cortical SUVR from the proposed synthetic MRI agreed closely with the real MRI-based reference (MAE 0.016 ± 0.015, Pearson $r = 0.9987$) and yielded the same amyloid-positivity classification as the real MRI in all 87 test subjects at the prespecified cut-off. Conformal prediction achieved empirical coverage close to the prespecified levels, and at 90% target coverage, 85 of 87 subjects had prediction intervals that supported an unambiguous amyloid-positivity decision. Zero-shot evaluation on an independent external cohort showed that the proposed CT-to-MRI model could support PET quantification without retraining, although conformal calibration required target-cohort recalibration to recover the intended coverage. These findings support CT-to-MRI-based MRI-free PET quantification as a promising approach for providing accurate SUVR measurements and an explicit assessment of their reliability.