[18F]MK-6240 is a second-generation tau PET-tracer to quantify neurofibrillary tangles in-vivo. However, individually variable levels of meningeal uptake induce spill-in-effects into the cortex, complicating [18F]MK-6240 PET quantification. Group SUVR differences between age-matched HC subgroups with varying extracerebral uptake (EC-low/mixed/high), and between aMCI and each HC subgroup were assessed without and with partial volume correction (PVC). Both Müller-Gartner (MG-)PVC and region-based voxelwise (RBV-)PVC, with the latter also correcting for extracerebral spill-in-effects, were implemented. Between HC groups, where no differences are to be expected, HC EC-high showed spill-in differences compared to HC EC-low when no PVC was applied while for MG-PVC, differences were reduced and, for RBV-PVC, no statistically significant differences were observed. Between aMCI and HC, cortical SUVR differences were statistically significant, both without and with PVC, but modulated by the varying meningeal uptake in HC subgroups when no PVC was applied. After applying PVC, correlations to clinical parameters improved and effect sizes between HC and aMCI increased, independent of the HC-subgroup. Therefore, appropriate PVC with correction for extracerebral spill-in-effects is recommended to minimize the impact of varying meningeal uptake on cortical differences between HC and aMCI.
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