Neuroimaging biomarkers predict brain structural connectivity change in a mouse model of vascular cognitive impairment

Boehm-Sturm, Philipp and Füchtemeier, Martina and Foddis, Marco and Mueller, Susanne and Trueman, Rebecca C. and Zille, Marietta and Rinnenthal, Jan Leo and Kypraios, Theodore and Shaw, Laurence and Dirnagl, Ulrich and Farr, Tracy D. (2017) Neuroimaging biomarkers predict brain structural connectivity change in a mouse model of vascular cognitive impairment. Stroke, 48 (1). pp. 1-9. ISSN 1524-4628

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Abstract

Background and Purpose—Chronic hypoperfusion in the mouse brain has been suggested to mimic aspects of vascular cognitive impairment, such as white matter damage. Although this model has attracted attention, our group has struggled to generate a reliable cognitive and pathological phenotype. This study aimed to identify neuroimaging biomarkers of brain pathology in aged, more severely hypoperfused mice.

Methods—We used magnetic resonance imaging to characterize brain degeneration in mice hypoperfused by refining the surgical procedure to use the smallest reported diameter microcoils (160 μm).

Results—Acute cerebral blood flow decreases were observed in the hypoperfused group that recovered over 1 month and coincided with arterial remodeling. Increasing hypoperfusion resulted in a reduction in spatial learning abilities in the water maze that has not been previously reported. We were unable to observe severe white matter damage with histology, but a novel approach to analyze diffusion tensor imaging data, graph theory, revealed substantial reorganization of the hypoperfused brain network. A logistic regression model from the data revealed that 3 network parameters were particularly efficient at predicting group membership (global and local efficiency and degrees), and clustering coefficient was correlated with performance in the water maze.

Conclusions—Overall, these findings suggest that, despite the autoregulatory abilities of the mouse brain to compensate for a sudden decrease in blood flow, there is evidence of change in the brain networks that can be used as neuroimaging biomarkers to predict outcome.

Item Type: Article
Keywords: biomarkers, diffusion tensor imaging, hypoperfusion, magnetic resonance imaging, mouse, neuroimaging, vascular cognitive impairment
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
Identification Number: 10.1161/STROKEAHA.116.014394
Depositing User: Eprints, Support
Date Deposited: 13 Jan 2017 11:32
Last Modified: 26 May 2017 00:17
URI: http://eprints.nottingham.ac.uk/id/eprint/39844

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