Abstract

Microstructure imaging by means of multidimensional diffusion encoding is increasingly applied in clinical research, with expectations that it yields a parameter that better correlates with clinical disability than current methods based on single diffusion encoding. Under the assumption that diffusion within a voxel can be well described by a collection of diffusion tensors, several parameters of this diffusion tensor distribution can be derived, including mean size, variance of sizes, orientational dispersion, and microscopic anisotropy. The information provided by multidimensional diffusion encoding also enables us to decompose the sources of the conventional fractional anisotropy and mean kurtosis. In this study, we explored the utility of the diffusion tensor distribution approach for characterizing white-matter degeneration in aging and in Parkinson disease by using double diffusion encoding. Data from 23 healthy older subjects and 27 patients with Parkinson disease were analyzed. Advanced age was associated with greater mean size and size variances, as well as smaller microscopic anisotropy. By analyzing the parameters underlying diffusion kurtosis, we found that the reductions of kurtosis in aging and Parkinson disease reported in the literature are likely driven by the reduction in microscopic anisotropy. Furthermore, microscopic anisotropy correlated with the severity of motor impairment in the patients with Parkinson disease. The present results support the use of multidimensional diffusion encoding in clinical studies and are encouraging for its future clinical implementation.

Highlights

  • Parkinson disease (PD) is a neurodegenerative disorder characterized by motor symptoms and a wide range of cognitive, neuropsychiatric, and autonomic dysfunctions (Poewe et al, 2017)

  • The present results suggest that the measures of microscopic anisotropy (Kaniso and μFA) might be useful to track white-matter degeneration related to the motor impairment in PD

  • We explored the utility of double diffusion encoding (DDE)-derived parameters for characterizing white-matter degeneration in aging and PD

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Summary

Introduction

Parkinson disease (PD) is a neurodegenerative disorder characterized by motor symptoms (akinesia, resting tremor, and rigidity) and a wide range of cognitive, neuropsychiatric, and autonomic dysfunctions (Poewe et al, 2017). Advanced age is a major risk factor for the development of PD and is associated with faster motor decline (Levy, 2007; Collier et al, 2017). PD is characterized by widespread aggregation of α-synuclein-immunoreactive inclusions in the form of Lewy pathology within both the neuronal cytoplasm (Lewy bodies) and axons (Lewy neurites) (Braak et al, 2003; Kanazawa et al, 2012; Poewe et al, 2017). Accumulating evidence has suggested that axonal degeneration is an early event in the process of neurodegeneration that is common to PD and other age-related neurological diseases (Kurowska et al, 2016; Salvadores et al, 2017). Non-invasive characterization of the neurodegeneration underlying the pathogenesis and progression of PD is of high clinical demand, because it will aid in the development of novel therapeutic strategies and in monitoring the effects of treatment

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