title: Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke.
abstract: Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia-ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24  hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.
authors.affiliation: Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shereen
authors.forename: Niza
authors.initials: N
authors.lastname: Nemkul
authors.forename: Dianer
authors.initials: D
authors.lastname: Yang
authors.forename: Faisal
authors.initials: F
authors.lastname: Adhami
authors.forename: R Scott
authors.initials: RS
authors.lastname: Dunn
authors.forename: Missy L
authors.initials: ML
authors.lastname: Hazen
authors.forename: Masato
authors.initials: M
authors.lastname: Nakafuku
authors.forename: Gang
authors.initials: G
authors.lastname: Ning
authors.forename: Diana M
authors.initials: DM
authors.lastname: Lindquist
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Kuan
mesh_terms: D000818:Animals; D016880:Anisotropy; D001370:Axonal Transport / Q000502:physiology; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D002534:Hypoxia, Brain / Q000150:complications / Q000473:pathology*; D007150:Immunohistochemistry; D020767:Intracranial Thrombosis / Q000150:complications / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D020521:Stroke / Q000209:etiology / Q000473:pathology*; D013997:Time Factors