Gray to white matter signal ratio as a novel biomarker of neurodegeneration in Alzheimer’s disease

Deepti Putcha; Yuta Katsumi; Michael Brickhouse; Ryn Flaherty; David H. Salat; Alexandra Touroutoglou; Bradford C. Dickerson

NeuroImage: Clinical (Jan 2023)

Gray to white matter signal ratio as a novel biomarker of neurodegeneration in Alzheimer’s disease

Deepti Putcha,
Yuta Katsumi,
Michael Brickhouse,
Ryn Flaherty,
David H. Salat,
Alexandra Touroutoglou,
Bradford C. Dickerson

Affiliations

Deepti Putcha: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Corresponding authors at: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Yuta Katsumi: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Corresponding authors at: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Michael Brickhouse: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Ryn Flaherty: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
David H. Salat: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA
Alexandra Touroutoglou: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Massachusetts Alzheimer’s Disease Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Corresponding authors at: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Bradford C. Dickerson: Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Massachusetts Alzheimer’s Disease Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

Journal volume & issue: Vol. 37
p. 103303

Abstract

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Alzheimer’s disease (AD) is characterized neuropathologically by β-amyloid (Aβ) plaques, hyperphosphorylated tau neurofibrillary tangles, and neurodegeneration, which lead to a phenotypically heterogeneous cognitive-behavioral dementia syndrome. Our understanding of how these neuropathological and neurodegeneration biomarkers relate to each other is still evolving. A relatively new approach to measuring structural brain change, gray matter to white matter signal intensity ratio (GWR), quantifies the signal contrast between these tissue compartments, and has emerged as a promising marker of AD-related neurodegeneration. We sought to validate GWR as a novel MRI biomarker of neurodegeneration in 29 biomarker positive individuals across the atypical syndromic spectrum of AD. Bivariate correlation analyses revealed that GWR was associated with cortical thickness, tau PET, and amyloid PET, with GWR showing a larger magnitude of abnormality than cortical thickness. We also found that combining GWR, cortical thickness, and amyloid PET better explained observed tau PET signal than using these modalities alone, suggesting that the three imaging biomarkers contribute independently and synergistically to explaining the variance in the distribution of tau pathology. We conclude that GWR is a uniquely sensitive in vivo marker of neurodegenerative change that reflects pathological mechanisms which may occur prior to cortical atrophy. By using all of these imaging biomarkers of AD together, we may be better able to capture, and possibly predict, AD neuropathologic changes in vivo. We hope that such an approach will ultimately contribute to better endpoints to evaluate the efficacy of therapeutic interventions as we move toward an era of disease-modifying treatments for this devastating disease.

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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