Our patients objective is to eliminate gadolinium (Gd) injections i n routine follow-up MRI of multiple sclerosis (MS) using quantitative susceptibility mapping (QSM) asa direct response to the calls issued by the NIH and FDA to re-evaluate repetitive Gd administration to patients. We have pioneered QSM that is generated by processing the often-discarded phase data from gradient echo MRI (GRE). We have discovered that iron- containing proinflammatory microglia often accumulate at the MS lesion rim. We have initiated applications of QSM in studying multiple sclerosis, and have demonstrated that QSM can detect iron rims around MS lesions. We have obtained preliminary data in MS patients that the susceptibility increase as measured on QSM can accurately indicate BBB closure, as supported by the biophysics of myelin digestion, myelin debris removal, and iron accumulation. Totranslate our pathophysiologic and biophysical insights into patient care,we propose a no-Gd MRI using QSM to follow up MS patients. We will perform an economical multicenter study by adding a 5 min GRE sequence to the current MS MRI follow-up protocol without incurring any scan costs to the NIH. We will employ a hierarchical approach to assess the technical efficacy, diagnostic accuracy, diagnostic thinking, and therapeutic efficacy of the proposed QSM based no-Gd MRI. Accordingly, we plan to achieve our objective through the following specific aims: Aim 1: Establish susceptibility increase due to myelin digestion by macrophages. Aim 2: Optimize the technical efficacy of no-Gd MRI to follow up MS patients. Aim 3: Evaluate the diagnostic accuracy, diagnostic thinking, and therapeutic efficacy of QSM based no-Gd MRI.

The NIH, FDA, ISMRM (International Society of Magnetic Resonance in Medicine), and CMSC (Consortium of Multiple Sclerosis Centers) have requested healthcare professionals to reassess the necessity of administering gadolinium (Gd) contrast agents in Multiple Sclerosis (MS) monitoring with repetitive MRIs, because Gd accumulates in the brain with unknown risks. MS patients typically develop the disease at a young age and have regular MRIs over their lifetimes with great risk of Gd accumulation in their brains. This project and barrier a research will develop a no-Gd MRI for following up MS patients using quantitative susceptibility mapping (QSM) wil l establish that t his QSM based no-Gd MRI is as accurate as current Gd MRI for indicating blood brain leakage, and is superior to current Gd MRI for monitoring microglia inflammation in the MS brain behind closed blood brain barrier.