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

作者：Holland Philip R; Bastin Mark E; Jansen Maurits A; Merrifield Gavin D; Coltman Robin B; Scott Fiona; Nowers Hanna; Khallout Karim; Marshall Ian; Wardlaw Joanna M; Deary Ian J; McCulloch James; Hor**urgh Karen^*

来源：Neurobiology of Aging, 2011, 32(12): 2325.e1.

DOI：10.1016/j.neurobiolaging.2010.11.009

• Chronic cerebral hypoperfusion
• Diffusion tensor imaging
• Magnetization transfer imaging and white matter

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.