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White matter microstructural alterations and their correlations to neuropsychological measures

Target audience: Clinicians and MR physicists who are interested in predicting functional consequences with categorized tract-level white matter disruption detected from measurements of DTI-derived metrics in study of multiple sclerosis. Introduction and Purpose: Diffusion Tensor Imaging (DTI) is capable of quantifying white-matter (WM) microstructural changes of patients with neurological diseases such as Multiple Sclerosis (MS). The four DTI-derived metrics, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) capture different aspects of white matter microstructural alterations (1) and were applied in this study. The WM can be generally categorized into four tract groups, commissural, limbic, association and projection tracts, based on their functions (2). Whereas extensive previous work has documented MS-related WM changes, there has been minimal work investigating the functional consequences of these changes. In this study we assessed the sensitivity of the four DTI metrics in these four tract groups to MS WM pathology and performance changes, assessed by neuropsychological measures. Methods: Participants: 13 patients (age=47+6.6) diagnosed with MS and 12 age-matched healthy controls (age=42+9.7) performed a neuropsychological tests battery including Selective Reminding Task Long Term Storage (SRT-LTS) and Symbol-digit modalities Task (SDMT). DTI acquisition: Data were acquired using a single-shot EPI with SENSE on a 3T Philips Achieva MR system. DWI parameters: FOV=224/224/143mm, inplane imaging matrix=112×112, axial slice thickness=2.2 mm, no gap, slice number=65, 30 independent diffusion-weighted directions with b-value=1000 sec/mm, repetitions=2. Voxelwise analysis: TBSS from FMRIB software library was used for voxel-wise comparison. The single subject template used for nonlinear registration process in TBSS (3) is identical to that used for establishing JHU ICBM-DTI-81 (4). After statistical analysis from TBSS, significant clusters (p < .001; uncorrected) in the skeleton voxels of WM were identified. To avoid false positives due to noise, only clusters with continuous voxels larger than 10 were retained for the four DTI metrics FA, RD, AD and MD. Tract-level comparison: Tract-level analysis was based on FA values at the skeleton voxels after TBSS registration, projection and skeletonization steps. Average DTI metrics were calculated in each tract before student’s t-test. Correlation to neuropsychological measures: DTI metrics averaged at the significant clusters were correlated with SRT-LTS and SDMT.