Author

Art Riddle

Date

July 2011

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Objective: Although periventricular white matter injury (WMI) is the leading cause of chronic neurological disability and cerebral palsy in survivors of premature birth, the cellular-molecular mechanisms, histopathological features and neuroimaging indicators of diffuse WMI are poorly defined. Methods: To define pathophysiologic relationships among ischemia, acute cerebral white matter damage, and vulnerable target populations, we used a global cerebral ischemia-reperfusion model in the instrumented 0.65 gestation fetal sheep model. We developed a novel method for repeated measurements of cerebral blood flow using fluorescently labeled microspheres to resolve the spatial heterogeneity of flow in situ in three-dimensional space. We also developed novel algorithms to register histopathologically defined lesions with contrast- and diffusion-weighted high-field ex vivo MRI data. Combined electron microscopic techniques and MRI were used to assess the burden of axonal injury. Results: Basal

Identifier

doi:10.6083/M41J97RT

Division

Neuroscience Graduate Program

School

School of Medicine

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