Project Summary We propose to develop and optimize Susceptibility Weighted MRI (SWI) for the human SC in vivo at 7T and 3T and apply/evaluate/validate in patients with MS to identify abnormal venous hallmarks of MS pathology. We observed abnormally large anterior/posterior spinal veins, central vein sign (CVS), paramagnetic rims around lesions and increased contrast from the venous plexus surrounding the SC are all present in the MS SC compared to healthy volunteers. Yet, SC SWI has not been adequately optimized and validated at any field strength. We address the knowledge gap of understudied SC SWI, and evaluating and validating in MS, opening the door for application to pathologies that have previously been studied in the brain such as traumatic injury, microbleeds, SC compression, and other vascular abnormalities. Our goal is to develop, optimize, and apply/evaluate/validate SC SWI using both clinical (3T) and research (7T) field strengths in healthy controls relapsing-remitting MS patients. SWI has implemented clinically in the brain for years. Recent work show that 7T and 3T SWI is useful for improving diagnostic specificity in MS, providing evidence for expanding/evolving lesions, and insight into the biogenesis and evolution of the disease. While the same literature points to the need to evaluate the SC with SWI, and post-mortem indicates similar pathological hallmarks in the SC in MS, to date, exceedingly few studies have attempted SC SWI. And in those, brain-optimized SWI were moved into the SC. There are no SC targeted developmental SWI studies and no studies at 7T. Of course, application of developed techniques is critical to the validation process. One of the radiological “wins” for MS has been identifying hallmark central vein sign (CVS) and/or paramagnetic rims indicating lesion evolution which has led to controversial discussions about improved diagnostic specificity. Recently a consensus prepared by the North American Imaging in MS consortium (NAIMS), of which the PI is a contributor, describes expectations for brain SWI and argues for SC SWI to solidify SWI as improving diagnostic specificity. Yet there are no studies providing this evidence. Operating under the premise that brain SWI has provided rich information about diseases such as MS, TBI, etc, has improved our understanding of MS and MS lesion evolution, and armed with our preliminary data at 7T that demonstrates MS patients have 1) abnormally large anterior spinal veins, 2) some lesions have apparent CVW and paramagnetic rim, and 3) abnormally apparent venous plexus surrounding the SC, we propose that developing and optimizing a SC-specific SWI acquisition and post- processing toolbox would offer unique ability to assess the venous structures of the SC and lead to further opportunities in other diseases. 7T is considered the gold standard for SWI in MS in the brain, and we will explore that, but recognize that 3T is more clinically relevant. Thus we will optimize across both 3T and 7T using vendor stock sequences and advanced, sequences. The former to provide consideration for multi- vendor, multi-site studies, and the latter, to vet and validate SWI as a biomarker for SC vascular abnormalities.

Project Narrative Multiple sclerosis (MS) is one of the most prevalent (~1 million MS patients in the US) and debilitating neurological diseases that affects patients in early adulthood and is the second leading cause of non-traumatic paralysis. In the brain, in MS, hallmark signatures derived from susceptibility weighted MRI (SWI) have provided insight into the biogenesis, evolution, and improved diagnostic specificity of the disease but SWI has even shown utility beyond MS for detecting and quantifying iron accumulation, vascular leakage, microbleeds, and traumatic injury. SWI of the spinal cord is understudied, but if optimized, deployed, and validated in MS, identifying similar hallmarks as seen in the brain would 1) provide insight into MS disease, 2) provide a tool that can be utilized in the spinal cord for other conditions and 3) address a knowledge gap of quality, vetted, SWI for the human spinal cord in vivo.