Fixel-Based Analysis of White Matter Degeneration in Patients With Progressive Supranuclear Palsy or Multiple System Atrophy, as Compared to Parkinson's Disease.

Thanh-Thao Nguyen,Chih-Chien Tsai,Jur-Shan Cheng,Yi-Hsin Weng,Chin-Song Lu,Yao-Liang Chen,Jiun-Jie Wang,Yu-Chun Lin,Yi-Ming Wu,Ngoc-Thanh Hoang

doi:10.3389/fnagi.2021.625874

Abstract

Introduction: White matter degeneration may contribute to clinical symptoms of parkinsonism.Objective: We used fixel-based analysis (FBA) to compare the extent and patterns of white matter degeneration in different parkinsonian syndromes—including idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).Methods: This is a retrospective interpretation of prospectively acquired data of patients recruited in previous studies during 2008 and 2019. Diffusion-weighted images were acquired on a 3-Tesla scanner (diffusion weighting b = 1000 s/mm2–applied along either 64 or 30 non-collinear directions) from 53 patients with PD (men/women: 29/24; mean age: 65.06 ± 5.51 years), 47 with MSA (men/women: 20/27; mean age: 63.00 ± 7.19 years), and 50 with PSP men/women: 20/30; mean age: 65.96 ± 3.14 years). Non-parametric permutation tests were used to detect intergroup differences in fixel-related indices—including fiber density, fiber cross-section, and their combination.Results: Patterns of white matter degeneration were significantly different between PD and atypical parkinsonisms (MSA and PSP). Compared with patients with PD, those with MSA and PSP showed a more extensive white matter involvement—noticeably descending tracts from primary motor cortex to corona radiata and cerebral peduncle. Lesions of corpus callosum were specific to PSP and absent in both MSA and PD.Discussion: FBA identified specific patterns of white matter changes in MSA and PSP patients compared to PD. Our results proved the utility of FBA in evaluation of implied biological processes of white matter changes in parkinsonism. Our study set the stage for future applications of this technique in patients with parkinsonian syndromes.

Highlights

White matter degeneration may contribute to clinical symptoms of parkinsonism
fixel-based analysis (FBA) was used to assess the patterns of white matter changes in three different forms of parkinsonism
Our findings revealed profound differences in terms of white matter involvement among groups—with affected regions being more extensive in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) than in Parkinson’s disease (PD)

Summary

Introduction

White matter degeneration may contribute to clinical symptoms of parkinsonism. Parkinsonism is a progressive neurodegenerative disorder characterized by resting tremor, rigidity, bradykinesia/akinesia, and postural instability (McFarland, 2016). Extensive involvement of different brain regions is accompanied by white matter degeneration, which may result in a clinically relevant functional decline (Whitwell et al, 2011). Erroneous interpretations in DTI may result from oversimplification of the underlying anatomical structures (Mori and Zhang, 2006; Chen et al, 2019), especially in regions with crossing fibers (Jbabdi et al, 2010). In this scenario, fixel-based analysis (FBA) has emerged as a novel approach based on a higher-order diffusion model to compute fiber orientation density function (Raffelt et al, 2017). Three fixelbased indices can be derived, which are fiber density (FD)—the volume of intra-axonal space of particular fixel; fiber crosssection (FC)—the cross-sectional area of particular fixel; and the combination of fiber density and cross-section (FDC) (Pecheva et al, 2019)

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