In vivo assessment of neurodegeneration in Spinocerebellar Ataxia type 7

Jacob A. Parker; Shabbir H. Merchant; Sanaz Attaripour-Isfahani; Hyun Joo Cho; Patrick McGurrin; Brian P. Brooks; Albert R. La Spada; Mark Hallett; Laryssa A. Huryn; Silvina G. Horovitz

NeuroImage: Clinical (Jan 2021)

In vivo assessment of neurodegeneration in Spinocerebellar Ataxia type 7

Jacob A. Parker,
Shabbir H. Merchant,
Sanaz Attaripour-Isfahani,
Hyun Joo Cho,
Patrick McGurrin,
Brian P. Brooks,
Albert R. La Spada,
Mark Hallett,
Laryssa A. Huryn,
Silvina G. Horovitz

Affiliations

Jacob A. Parker: Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Shabbir H. Merchant: Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Medical University of South Carolina, Charleston, SC, USA
Sanaz Attaripour-Isfahani: Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, University of California Irvine School of Medicine, Irvine, CA, USA
Hyun Joo Cho: Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Patrick McGurrin: Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Brian P. Brooks: Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Albert R. La Spada: Department of Neurology, University of California Irvine School of Medicine, Irvine, CA, USA; Department of Pathology & Laboratory Medicine, University of California, Irvine, CA, USA; UCI Institute for Neurotherapeutics, University of California, Irvine, CA 92697, USA
Mark Hallett: Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Laryssa A. Huryn: Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Silvina G. Horovitz: Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Corresponding author at: Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. 7D37, Bethesda, MD 20892-1428, USA.

Journal volume & issue: Vol. 29
p. 102561

Abstract

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Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive cerebellar ataxia and retinal degeneration. Increasing loss of visual function complicates the use of clinical scales to track the progression of motor symptoms, hampering our ability to develop accurate biomarkers of disease progression, and thus test the efficacy of potential treatments. We aimed to identify imaging measures of neurodegeneration, which may more accurately reflect SCA7 severity and progression. While common structural MRI techniques have been previously used for this purpose, they can be biased by neurodegeneration-driven increases in extracellular CSF-like water. In a cross-sectional study, we analyzed diffusion tensor imaging (DTI) data collected from a cohort of 13 SCA7 patients and 14 healthy volunteers using: 1) a diffusion tensor-based image registration technique, and 2) a dual-compartment DTI model to control for the potential increase in extracellular CSF-like water. These methodologies allowed us to assess both volumetric and microstructural abnormalities in both white and gray matter brain-wide in SCA7 patients for the first time. To measure tissue volume, we performed diffusion tensor-based morphometry (DTBM) using the tensor-based registration. To assess tissue microstructure, we computed the parenchymal mean diffusivity (pMD) and parenchymal fractional anisotropy (pFA) using the dual compartment model. This model also enabled us to estimate the parenchymal volume fraction (pVF), a measure of parenchymal tissue volume within a given voxel. While DTBM and pVF revealed tissue loss primarily in the brainstem, cerebellum, thalamus, and major motor white matter tracts in patients (p 1), pMD and pFA detected microstructural abnormalities in virtually all tissues brain-wide (p 1). The Scale for the Assessment and Rating of Ataxia trended towards correlation with cerebellar pVF (r = −0.66, p = 0.104, FDR corrected) and global white matter pFA (r = −0.64, p = 0.104, FDR corrected). These results advance our understanding of neurodegeneration in living SCA7 patients by providing the first voxel-wise characterization of white matter volume loss and gray matter microstructural abnormalities. Moving forward, this comprehensive approach could be applied to characterize the full spatiotemporal pattern of neurodegeneration in SCA7, and potentially develop an accurate imaging biomarker of disease progression.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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