title: Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging.
abstract: Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior-posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations.
authors.affiliation: Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Nan-Jie
authors.initials: NJ
authors.lastname: Gong
authors.affiliation: Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Electronic address: drcswong@hku.hk.
authors.forename: Chun-Sing
authors.initials: CS
authors.lastname: Wong
authors.affiliation: Department of Geriatrics & Medicine, United Christian Hospital, Hong Kong, China.
authors.forename: Chun-Chung
authors.initials: CC
authors.lastname: Chan
authors.affiliation: Department of Psychiatry, United Christian Hospital, Hong Kong, China.
authors.forename: Lam-Ming
authors.initials: LM
authors.lastname: Leung
authors.affiliation: Department of Radiology, Kwong Wah Hospital, Hong Kong, China.
authors.forename: Yiu-Ching
authors.initials: YC
authors.lastname: Chu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D003071:Cognition; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D066128:Gray Matter / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology* / Q000502:physiology
keywords: Age; Alzheimer's disease; Diffusion tensor imaging; Diffusional kurtosis imaging; Gray matter; White matter