Tract-specific analysis improves sensitivity of spinal cord diffusion MRI to cross-sectional and longitudinal changes in amyotrophic lateral sclerosis

Pramod Kumar Pisharady,David Walk,Gaurav Guliani,Christophe Lenglet,H Brent Clark,Georgios Manousakis,Ian Cheong,Mark Bathe,Lynn E Eberly

doi:10.1038/s42003-020-1093-z

Abstract

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease that causes progressive degeneration of motor neurons in the brain and the spinal cord. Corticospinal tract degeneration is a defining feature of ALS. However, there have been very few longitudinal, controlled studies assessing diffusion MRI (dMRI) metrics in different fiber tracts along the spinal cord in general or the corticospinal tract in particular. Here we demonstrate that a tract-specific analysis, with segmentation of ascending and descending tracts in the spinal cord white matter, substantially increases the sensitivity of dMRI to disease-related changes in ALS. Our work also identifies the tracts and spinal levels affected in ALS, supporting electrophysiologic and pathologic evidence of involvement of sensory pathways in ALS. We note changes in diffusion metrics and cord cross-sectional area, with enhanced sensitivity to disease effects through a multimodal analysis, and with strong correlations between these metrics and spinal components of ALSFRS-R.

Highlights

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease that causes progressive degeneration of motor neurons in the brain and the spinal cord
In this study, we present findings of tractography along the cord and extracted diffusion metrics along spinal pathways to analyze their continuous variation from C2 to C6 in people with ALS and an equivalent number of healthy control participants at enrollment and longitudinally over 1 year
This tractography-based approach facilitates between-subject statistical analysis tailored to the specific anatomy of each participant14, potentially resulting in more accurate inter-group comparison

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease that causes progressive degeneration of motor neurons in the brain and the spinal cord. In a longitudinal study of ALS patients and healthy controls utilizing a 1.5 T scanner, Agosta et al. reported decreased FA, increased MD, and decreased cord cross-sectional area (CSA) in whole cervical cord in ALS patients over time. These imaging changes did not correlate with functional decline, their mean followup was relatively brief (9 months). FA is extracted from manual segmentation of the CST through the entire C2-T2 region They found significant correlations between FA and the ALS Functional Rating Scale-Revised (ALSFRS-R) leg sub-score and between cord CSA and the ALSFRS-R arm sub-score at baseline and follow-up scans. Prior studies have varied considerably in many features, including field strength, cord segments analyzed, extent of cord segmentation, the presence or absence of a healthy control cohort, and the presence or absence of longitudinal data

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Conclusion