Diffusion MRI‐derived free water fraction may be a sensitive imaging biomarker that could improve identification of mild cognitive impairment participants progressing to Alzheimer’s disease dementia

Abstract

AbstractBackgroundWe hypothesize that diffusion MRI (dMRI)‐derived free‐water‐fraction (fiso) of not only hippocampus but also of limbic and temporal cortex along with fiso of white matter (WM) of cingulate, corpus‐callosum, and frontotemporal tracts will show significant difference in participants progressing to Alzheimer’s disease (AD)‐dementia as compared to non‐progressors. Incorporating these measures may improve identification of mild cognitive impairment (MCI) participants progressing to AD‐dementia.Method7 MCI‐Stable (M2M) and 4 MCI‐Converters (M2A) over a period of one‐year, each with at least one ε4 allele, positive PET‐quantified amyloid‐beta, and matched demographics were recruited at our center. MCI and AD diagnoses were based on expert consensus, using results of a neuropsychological test battery and the Clinical Dementia Rating (CDR) interview. Isotropic 1mm3 T1‐weighted MPRAGE along with a 213 directions multi‐shell dMRI (b‐values=500s/mm2, 1000s/mm2, and 2500s/mm2) at an isotropic 1.5mm3 resolution was acquired on a 3T Siemens Skyra scanner. Average volumes and fiso within each FreeSurfer defined region‐of‐interest (ROI), and average fiso in twenty major WM fiber tracts was estimated for each participant at each timepoint. Only those ROIs and WM fiber tracts that showed at least 10% change in fiso longitudinally within each group were selected for further analysis.ResultBilateral hippocampus showed lower volume (Figure 1) and elevated fiso (Figure 2) within M2A group. However, volume of other ROIs (e.g.: Anterior corpus callosum, posterior cingulate cortex, tranverse‐temporal cortex etc.) did not show a lower volume longitudinally, even though there was a 10% increase in fiso longitudinally in those ROIs. Furthermore, a complex correlation between fiso and volume was observed at each timepoint (Figure 3). Interestingly, hippocampal tail was found to be driving the effect seen in right hippocampus, with an opposite slope at each timepoint between M2A and M2M group (Figure 4). Contrary to our hypothesis, right cingulate WM tract and genu of corpus‐callosum (FMinor) showed a decrease in fiso within M2A group (Figure 5).ConclusionOur pilot analysis, albeit with small sample size and potentially underpowered, revealed that fiso of tail of hippocampus, frontal and temporal cortex, and WM fibers of limbic cortex and FMinor may be included as potential predictive imaging biomarkers of AD‐dementia from MCI.