An exploratory synthetic MRI-derived FLAIR-DIR contrast in olfactory-limbic regions in mild cognitive impairment

BackgroundOdor identification impairment is an early feature of Alzheimer's disease and predicts memory decline, but its microstructural basis remains unclear.ObjectiveTo evaluate FD, a semi-quantitative synthetic magnetic resonance imaging (MRI)-derived Fluid-Attenuated Inversion Recovery (FLAIR)-Double Inversion Recovery (DIR) contrast, against myelin volume fraction (MVF) in olfactory-limbic brain regions of patients diagnosed with mild cognitive impairment (MCI).MethodsSixteen healthy controls (HC) and 17 individuals diagnosed with MCI completed olfactory and cognitive testing and underwent 3T MRI using a QALAS sequence. MVF maps were generated and FD was computed as (FLAIR - DIR)/FLAIR. Group differences were examined in olfactory-limbic gray matter and associated white-matter tracts, and voxel-wise regression assessed FD-odor identification associations, including models adjusted for voxel-wise MVF. Region of interest and voxel-wise analyses were exploratory and largely uncorrected for multiple comparisons.ResultsCompared with HC, MCI showed lower FD across olfactory-limbic gray matter and white-matter pathways, including hippocampus, amygdala, orbitofrontal cortex, thalamus and corpus callosum, whereas MVF differences were more limited. Better odor identification was associated with higher FD in hippocampal/parahippocampal regions and insula, persisting after MVF adjustment. MVF showed positive associations in the right parahippocampal gyrus, left thalamus and genu of the corpus callosum. In an exploratory secondary analysis reported in the Supplemental Material, FD-based classification exceeded chance but was not separable from age alone.ConclusionsFD is a semi-quantitative relaxation-contrast metric showing regional patterns partially distinct from MVF. These exploratory findings require replication in larger, demographically matched, biomarker-confirmed cohorts before FD can be regarded as a marker of early olfactory-limbic microstructural change in MCI.