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

Boehm-Sturm, P, Füchtemeier, M, Foddis, M, Mueller, S, Trueman, RC, Zille, M, Rinnenthal, JL, Kypraios, T, Shaw, L ORCID: https://orcid.org/0000-0002-0832-964X, Dirnagl, U and Farr, TD, 2017. Neuroimaging biomarkers predict brain structural connectivity change in a mouse model of vascular cognitive impairment. Stroke: a Journal of Cerebral Circulation, 48 (2), pp. 468-475. ISSN 0039-2499

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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:	Journal article
Publication Title:	Stroke: a Journal of Cerebral Circulation
Creators:	Boehm-Sturm, P., Füchtemeier, M., Foddis, M., Mueller, S., Trueman, R.C., Zille, M., Rinnenthal, J.L., Kypraios, T., Shaw, L., Dirnagl, U. and Farr, T.D.
Publisher:	Wolters Kluwer Health, Inc. on behalf of the American Heart Association, Inc.
Date:	February 2017
Volume:	48
Number:	2
ISSN:	0039-2499
Identifiers:	Number Type 10.1161/strokeaha.116.014394 DOI
Rights:	© 2017 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
Divisions:	Schools > School of Science and Technology
Record created by:	Jill Tomkinson
Date Added:	18 Dec 2018 16:11
Last Modified:	18 Dec 2018 16:11
URI:	https://irep.ntu.ac.uk/id/eprint/35377

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