In multiple sclerosis (MS), an estimated 40% of spinal cord (SC) lesions are located in the thoracic and lumbar segments of the SC. These regions of the SC are associated with lower limb and bladder function, the most prevalent targets for neurological deficits in MS, but the thoracolumbar SC is significantly understudied and lesions here are rarely identified with clinical magnetic resonance imaging (MRI) protocols. Conventional clinical MRI for the thoracolumbar SC lacks sensitivity to lesions and microscopic pathology that may drive impairment, and is unable to discern the extent of demyelination or possible altered function of the lower cord. The overarching goal of this project is to develop and optimize MRI methods for quantitative characterization of tissue structure and function in the thoracolumbar SC in patients with MS. I will complete this goal in three aims:
Aim 1) Develop and optimize anatomical, diffusion, and resting-state functional MRI methods for the thoracolumbar SC at clinical field strength (3T), Aim 2) Quantify the reproducibility of the thoracolumbar MRI protocol in healthy volunteers and characterize biological variation (e.g. age and sex differences) in thoracolumbar cord structure and function, and Aim 3) Apply the multimodal MRI toolset to study relationships between MRI indices, biological variables (age, sex), and clinical measures of lower limb and bladder dysfunction in MS patients. Completion of these aims and the mentored training in clinical and immunological features of MS outlined in this proposal will provide me with technical training in advanced MRI pulse programming and methods development for the spinal cord, and expanded didactic training in immunology, sex differences in MS, neuromuscular physiology, and clinical management of MS. In addition to the technical expertise above, this grant will allow me to transition to independence as a translational imaging scientist. My institution has guaranteed at least 90% protected time to the proposed research and career development activities. My professional development will be guided by an interdisciplinary mentorship committee led by my primary mentor Dr. Seth Smith and co-mentors Dr. John Gore and Dr. Subramaniam Sriram. Dr. Smith is an expert in pulse programming and deployment of advanced MRI methods in clinical populations, and Drs. Gore and Siram are renowned for their work in biomedical imaging methods and applications and immunological factors in MS lesion recovery, respectively. I am capitalizing on Vanderbilt?s strengths in translational imaging research and readily available clinical subjects by working with mentors and collaborators in the Institute of Imaging Science and in clinical departments of the Vanderbilt University Medical Center. This makes Vanderbilt a unique and stimulating environment for professional development and completion of my proposed studies.
Lower limb and bladder dysfunction are highly prevalent symptoms affecting quality of life in multiple sclerosis, a neurological disease that results in demyelination and neurodegeneration in the brain and spinal cord. Although it is known that the thoracolumbar segments of the spinal cord are relevant to lower limb and bladder function and are involved in the pathology of multiple sclerosis, there is a lack of quantitative, advanced magnetic resonance imaging (MRI) methods targeting this critical anatomical site. The overall goals of this research are to 1) develop, optimize, and validate quantitative MRI methods for characterizing macrostructure, microstructure, and functional connectivity in the thoracolumbar spinal cord at 3 Tesla field strength and 2) evaluate these methods as potential biomarkers for neurological deficits in patients with multiple sclerosis.
