title: Sensitivity of diffusion MRI to perilesional reactive astrogliosis in focal ischemia.
abstract: Reactive astrogliosis is a response to injury in the central nervous system that plays an essential role in inflammation and tissue repair. It is characterized by hypertrophy of astrocytes, alterations in astrocyte gene expression and astrocyte proliferation. Reactive astrogliosis occurs in multiple neuropathologies, including stroke, traumatic brain injury and Alzheimer's disease, and it has been proposed as a possible source of the changes in diffusion magnetic resonance imaging (dMRI) metrics observed with these diseases. In this study, the sensitivity of dMRI to reactive astrogliosis was tested in an animal model of focal acute and subacute ischemia induced by the vasoconstricting peptide, endothelin-1. Reactive astrogliosis in perilesional cortex was quantified by calculating the astrocyte surface density as determined with a glial fibrillary acidic protein (GFAP) antibody, whereas perilesional diffusion changes were measured in vivo with diffusional kurtosis imaging. We found substantial changes in the surface density of GFAP-positive astrocyte processes and modest changes in dMRI metrics in the perilesional motor cortex following stroke. Although there are time point-specific correlations between dMRI and histological measures, there is no definitive evidence for a causal relationship.
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Weber
authors.affiliation: Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.|Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Clifford H
authors.initials: CH
authors.lastname: Chan
authors.affiliation: Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Xingju
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Maggioncalda
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Valiulis
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Lauer
authors.affiliation: Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, SAR, China.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Hui
authors.affiliation: Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.|Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jens H
authors.identifier: http://orcid.org/0000-0003-3219-4287
authors.initials: JH
authors.lastname: Jensen
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.|Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.|Department of Health Science and Research, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: DeAnna L
authors.initials: DL
authors.lastname: Adkins
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005911:Gliosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000293:injuries / Q000473:pathology; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
keywords: GFAP; MRI; astrogliosis; diffusion; imaging; ischemia; perilesional; stereology