Multi-parametric Magnetic Resonance Imaging of the Spinal Cord at 9.4T

Abstract

The measurement of functional connectivity within the spine based on detecting resting-state fluctuations in functional magnetic resonance imaging (fMRI) signals potentially provides a new tool for assessing spinal cord functional architecture, but only recently have such signals been reliably detected and reported. Little is known about whether the spinal cord is expected to demonstrate functional connectivity similar to the brain, nor where these signal variations originate, nor if they are detectable in rodents, which are commonly used as models of injury. The research in this thesis detects and evaluates these signals in non-human primate and rodent models, and performs correlated studies to understand their basis and evaluate their significance. Specifically, results demonstrated a high concordance between local field potentials and fMRI metrics in a resting state, and revealed the presence of an intrinsic functional architecture within gray matter of a single spinal segment. Consistent with human and non-human primate studies, functional connectivity between gray matter horns in rodents also presented larger and significant correlations when compared to control regions. In order to further demonstrate their functional relevance, a contusion injury model in rodents was studied to examine how resting-state functional connectivity is related to the integrity of the spine. In parallel, this thesis also examines what changes in tissue composition and microstructure are modulated by such disruptions, and whether novel multi-parametric MRI methods can detect relevant changes in tissues. Results showed a decrease of myelin content two weeks after injury, which was validated with histology, but interestingly did not correlate with behavioral recovery. Moreover, functional integrity of spinal gray matter, which was assessed using fMRI, revealed subtle decreases and increases in correlations below and above the injury respectively. As extensive research efforts continue to promote SCI patient recovery, the application of quantitative MRI may contribute to the design of effective therapeutic interventions as well as the evaluation of treatment outcomes.