Author's School

School of Engineering & Applied Science

Author's Department/Program

Mechanical Engineering and Materials Science

Language

English (en)

Date of Award

1-1-2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Philip Bayly

Abstract

Traumatic spinal cord injury: SCI) is the most devastating injury that often causes the victim permanent paralysis and undergo a lifetime of therapy and care. It is caused by a mechanical impact that ultimately causes pathophysiological consequences which at this moment in time are an unresolved scientific challenge of great social impact. Scientists have long used animal contusion models to study the pathophysiology of SCI in the discovery of progressive secondary tissue degeneration, demyelination, and apoptosis. More importantly, most therapies that have gone to human clinical trial were first validated in spinal cord contusion models. Magnetic resonance imaging: MRI) is the modality of choice to noninvasively detect the soft tissue injury, particularly suitable for assessing the tissue integrity in SCI. However, the convention MRI lacks capability of detecting and evaluating the injury severity acutely, probably resulting in lost opportunities of effective prognostication or treatment stratification for SCI patients. Diffusion Tensor Magnetic Resonance Imaging: DTMRI, DTI) is an emerging technique known to provide dynamic contrast reflecting the progression of the underlying pathology in CNS tissues. In this study, we hypothesized that axial: ||) and radial: λ^) diffusivity derived from DTI is sensitive to the pathological alteration in spinal cord white matter: WM) tract and could be used as potential biomarkers detecting and characterizing the axonal and myelin damage in SCI. A mouse model of contusion SCI was examined using DTI, behavioral assessment, and histology to test our hypothesis. Techniques employed including the simplification of diffusion weighting scheme, the implementation of diffusion weighted multiple spin-echo sequence, and verified for setting up the experimental protocol and data processing procedures. Secondly, the hypothesis was test on the projects comparing the change of these biomarkers on both the myelinated and dysmyelinated shiverer mice cooperating with histological analysis, and behavioral assessment. Finally, a finite element analysis: FEA) of contusion SCI was deployed to provide evidences of injury mechanics correlated with the injury patterns detected by diffusion MRI for a better characterized animal model of contusion SCI.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7K35RRD

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