Imprecise registration between positron emission tomography (PET) and anatomical magnetic resonance (MR) images is a critical source of error in MR imaging-guided partial volume correction (MR-PVC). Here, we propose a novel framework for image registration and partial volume correction, which we term PVC-optimized registration (PoR), to address imprecise registration. The PoR framework iterates PVC and registration between uncorrected PET and smoothed PV-corrected images to obtain precise registration. We applied PoR to the [11C]PiB PET data of 92 participants obtained from the Alzheimer’s Disease Neuroimaging Initiative database and compared the registration results, PV-corrected standardized uptake value (SUV) and its ratio to the cerebellum (SUVR), and intra-region coefficient of variation (CoV) between PoR and conventional registration. Significant differences in registration of as much as 2.74 mm and 3.02° were observed between the two methods (effect size < − 0.8 or > 0.8), which resulted in considerable SUVR differences throughout the brain, reaching a maximal difference of 62.3% in the sensory motor cortex. Intra-region CoV was significantly reduced using the PoR throughout the brain. These results suggest that PoR reduces error as a result of imprecise registration in PVC and is a useful method for accurately quantifying the amyloid burden in PET.
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