Diffusion Tensor Imaging Revealed Microstructural Changes in Normal-Appearing White Matter Regions in Relapsing-Remitting Multiple Sclerosis

Jianfeng Bao; Hui Tu; Yijia Li; Jubao Sun; Zhigang Hu; Fengshou Zhang; Jinghua Li

doi:10.3389/fnins.2022.837452

Diffusion Tensor Imaging Revealed Microstructural Changes in Normal-Appearing White Matter Regions in Relapsing-Remitting Multiple Sclerosis

Front Neurosci. 2022 Mar 2:16:837452. doi: 10.3389/fnins.2022.837452. eCollection 2022.

Authors

Jianfeng Bao^{1

2}, Hui Tu¹, Yijia Li¹, Jubao Sun³, Zhigang Hu¹, Fengshou Zhang¹, Jinghua Li¹

Affiliations

¹ College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China.
² Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
³ MRI Center, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.

Abstract

Background: Axons and myelin sheaths are the physical foundation for white matter (WM) to perform normal functions. Our previous study found the metabolite abnormalities in frontal, parietal, and occipital normal-appearing white matter (NAWM) regions in relapsing-remitting multiple sclerosis (RRMS) patients by applying a 2D ¹H magnetic resonance spectroscopic imaging method. Since the metabolite changes may associate with the microstructure changes, we used the diffusion tensor imaging (DTI) method to assess the integrity of NAWM in this study.

Method: Diffusion tensor imaging scan was performed on 17 clinically definite RRMS patients and 21 age-matched healthy controls on a 3.0-T scanner. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 19 predefined regions of interest (ROIs), which were generated by removing a mask of manually drawn probabilistic lesion map from the Johns Hopkins University white-matter atlas. The mean values of FA, MD, AD, and RD were compared between different groups in the same ROIs.

Results: A probabilistic lesion map was successfully generated, and the lesion regions were eliminated from the WM atlas. We found that the RRMS patients had significantly lower FA in the entire corpus callosum (CC), bilateral of anterior corona radiata, and right posterior thalamic radiation (PTR). At the same time, RRMS patients showed significantly higher MD in the bilateral anterior corona radiata and superior corona radiata. Moreover, all AD values increased, and the bilateral external capsule, PTR, and left tapetum NAWM show statistical significance. What is more, all NAWM tracts showed increasing RD values in RRMS patients, and the bilateral superior corona radiata, the anterior corona radiata, right PTR, and the genu CC reach statistical significance.

Conclusion: Our study revealed widespread microstructure changes in NAWM in RRMS patients through a ready-made WM atlas and probabilistic lesion map. These findings support the hypothesis of demyelination, accumulation of inflammatory cells, and axonal injury in NAWM for RRMS. The DTI-based metrics could be considered as potential non-invasive biomarkers of disease severity.

Keywords: diffusion tensor imaging; magnetic resonance imaging; normal-appearing white matter; probabilistic lesion map; relapsing-remitting multiple sclerosis; white matter tracts atlas.