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MRI is a sensitive marker of subtle white matter pathology in hypoperfused mice

Author(s): P. R. Holland, M. E. Bastin, M. A. Jansen, G. D. Merrifield, R. B. Coltman, F. Scott, H. Nowers, K. Khallout, I. Marshall, J. M. Wardlaw, I. J. Deary, J. McCulloch, K. Horsburgh

Abstract:
White matter (WM) abnormalities, possibly resulting from hypoperfusion, are key features of the aging human brain. It is unclear, however, whether in vivo magnetic resonance imaging (MRI) approaches, such as diffusion tensor and magnetization transfer MRI are sufficiently sensitive to detect subtle alterations to WM integrity in mouse models developed to study the aging brain. We therefore investigated the use of diffusion tensor and magnetization transfer MRI to measure structural changes in 4 WM tracts following 1 month of moderate hypoperfusion, which results in diffuse WM pathology in C57Bl/6J mice. Following MRI, brains were processed for evaluation of white and gray matter pathology. Significant reductions in fractional anisotropy were observed in the corpus callosum (p = 0.001) and internal capsule (p = 0.016), and significant decreases in magnetization transfer ratio were observed in the corpus callosum (p = 0.023), fimbria (p = 0.032), internal capsule (p = 0.046) and optic tract (p = 0.047) following hypoperfusion. Hypoperfused mice demonstrated diffuse axonal and myelin pathology which was essentially absent in control mice. Both fractional anisotropy and magnetization transfer ratio correlate with markers of myelin integrity/degradation and not axonal pathology. The study demonstrates that in vivo MRI is a sensitive measure of diffuse, subtle WM changes in the murine brain. (C) 2011 Elsevier Inc. All rights reserved.

Full version: Available here

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ISBN: 0197-4580
Publication Year: 2011
Periodical: Neurobiology of Aging
Periodical Number: 12
Volume: 32
Pages:
Author Address: Horsburgh, K Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Ctr Cognit & Neural Syst, 1 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Ctr Cognit & Neural Syst, Edinburgh EH8 9JZ, Midlothian, Scotland Univ Edinburgh, Scottish Imaging Network, Platform Sci Excellence SINAPSE, Div Clin Neurosci, Edinburgh EH8 9JZ, Midlothian, Scotland Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland