Correspondence of mean apparent propagator MRI metrics with phosphorylated tau and astrogliosis in chronic traumatic encephalopathy

Mihika Gangolli; Sinisa Pajevic; Joong Hee Kim; Elizabeth B Hutchinson; Dan Benjamini; Peter J Basser

doi:10.1093/braincomms/fcad253

Correspondence of mean apparent propagator MRI metrics with phosphorylated tau and astrogliosis in chronic traumatic encephalopathy

Brain Commun. 2023 Oct 5;5(5):fcad253. doi: 10.1093/braincomms/fcad253. eCollection 2023.

Authors

Mihika Gangolli^{1

2

3}, Sinisa Pajevic^{4

5}, Joong Hee Kim^{1

2

6}, Elizabeth B Hutchinson^{5

7}, Dan Benjamini^{1

8}, Peter J Basser^{1

5}

Affiliations

¹ Center for Neuroscience and Regenerative Medicine, Bethesda, MD 20817, USA.
² The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
³ Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Section on Critical Brain Dynamics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
⁷ Department of Biomedical Engineering, University of Arizona, Tucson, AZ 20892, USA.
⁸ Multiscale Imaging and Integrative Biophysics Unit, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Chronic traumatic encephalopathy is a neurodegenerative disease that is diagnosed and staged based on the localization and extent of phosphorylated tau pathology. Although its identification remains the primary diagnostic criteria to distinguish chronic traumatic encephalopathy from other tauopathies, the hyperphosphorylated tau that accumulates in neurofibrillary tangles in cortical grey matter and perivascular regions is often accompanied by concomitant pathology such as astrogliosis. Mean apparent propagator MRI is a clinically feasible diffusion MRI method that is suitable to characterize microstructure of complex biological media efficiently and comprehensively. We performed quantitative correlations between propagator metrics and underlying phosphorylated tau and astroglial pathology in a cross-sectional study of 10 ex vivo human tissue specimens with 'high chronic traumatic encephalopathy' at 0.25 mm isotropic voxels. Linear mixed effects analysis of regions of interest showed significant relationships of phosphorylated tau with propagator-estimated non-Gaussianity in cortical grey matter (P = 0.002) and of astrogliosis with propagator anisotropy in superficial cortical white matter (P = 0.0009). The positive correlation between phosphorylated tau and non-Gaussianity was found to be modest but significant (R² = 0.44, P = 6.0 × 10^-5) using linear regression. We developed an unsupervised clustering algorithm with non-Gaussianity and propagator anisotropy as inputs, which was able to identify voxels in superficial cortical white matter that corresponded to astrocytes that were accumulated at the grey-white matter interface. Our results suggest that mean apparent propagator MRI at high spatial resolution provides a means to not only identify phosphorylated tau pathology but also detect regions with astrocytic pathology and may therefore prove diagnostically valuable in the evaluation of concomitant pathology in cortical tissue with complex microstructure.

Keywords: MAP-MRI; chronic traumatic encephalopathy; diffusion imaging; k-means clustering; phosphorylated tau.

Published by Oxford University Press on behalf of the Guarantors of Brain 2023.

Abstract

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