Advanced diffusion‐MRI models reveals sex‐specific differences in white matter organization in patients with mild cognitive impairment. (1st February 2022) - Mishra, Virendra R.
Abstract: Background: Recent literature suggests that free‐water corrected (fiso ) diffusion MRI (dMRI) measures provide higher sensitivity as compared to conventional single‐tensor (ST) dMRI measures to understand white‐matter (WM) changes due to neurodegeneration. However, fiso ‐corrected dMRI measures are still biased at crossing‐fiber regions (CFR) of WM which are shown to be around 90% of the total WM voxels with conventional dMRI data acquisition. In this study, we systematically compared dMRI measures from ST‐dMRI, fiso ‐corrected ST‐dMRI measures, and measures from advanced dMRI models such as Diffusion Kurtosis Imaging (DKI) and Neurite Orientation Distribution and Density Imaging (NODDI) which are sensitive to CFRs. We hypothesize that these advanced dMRI models will be sensitive in understanding sex‐specific WM organizational changes at regional level in patients with Alzheimer's disease (AD)‐related mild cognitive impairment (MCI). Method: 40 healthy controls [HC; 21 Females (F), 19 Males (M)] and 38 MCI participants [13F, 25 M] were recruited at our center. MCI diagnoses were based on expert consensus between a neurologist (AR) and a neuropsychologist (JC) using results of a neuropsychological test battery and the Clinical Dementia Rating (CDR) interview. Isotropic 1.5mm 3 multi‐shell dMRI (b‐values=500s/mm 2, 1000s/mm 2, and 2500s/mm 2 ) each with identical 71 diffusion‐encoding directions was acquired on a 3T Siemens Skyra scanner for every participant using the CMRR sequence. 8 uniformly interspersed non‐diffusion‐weighted (b0) images were also acquired in the same run. ST, fiso ‐corrected, DKI, and NODDI dMRI measures were estimated for every brain voxel in‐house using the standard analytic tools. WM was skeletonized using FSL tools and statistical comparisons were done non‐parametrically using PALM tools. GLM was utilized to test for sex‐specific group effect. Significance was established at family‐wise error correction (FWE) pcorr <0.05. Result: Thalamocortical tracts of males in both HC and MCI showed a significantly higher axonal kurtosis (AK) and orientation density (ODI) derived from DKI and NODDI when compared to within‐group females. DKI also revealed presence of higher axonal water fraction (AWF) along the entire WM‐tracts between HC‐female and HC‐male, and lower mean kurtosis (MK) along the thalamic‐cortical tracts in HC‐females as compared to MCI‐females. Conclusion: Advanced dMRI‐models are sensitive to understand sex‐specific WM disorganization due to healthy ageing and MCI.