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

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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.

Original languageEnglish (US)
Article number370
JournalCommunications biology
Volume3
Issue number1
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
This study was partly supported by funding from the Bob Allison Ataxia Research Center, the Institute for Translational Neuroscience, the Curt O’Hagan ALS/PLS and ALS-Lou Gehrig funds of the University of Minnesota Foundation, NIH grants P41 EB015894, P41 EB027061, P30 NS076408, and NSF Physics of Living Systems grant PHY 1305537. We are grateful to the persons living with ALS, their families, and control participants who volunteered their time; without them this work would not be possible. We acknowledge Valerie Ferment, the clinical study coordinator, and Susan Rolandelli, RN, for study coordination, and Pamela Droberg, NP, for her assistance in recruitment. We also thankfully acknowledge the help received from Dr. Julien Cohen-Adad (Polytechnique Mon-tréal) for customizing the spinal cord toolbox to segment the spinal cord from our diffusion data.

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