# PET and MRI Evaluation of Cerebral Inflammation and Metabolic Stress in Relapsing Multiple Sclerosis > **NIH NIH K23** · WASHINGTON UNIVERSITY · 2024 · $232,918 ## Abstract ABSTRACT Multiple sclerosis (MS) is an immune-mediated, demyelinating, and degenerative disease of the central nervous system and is a leading cause of disability in young people. Most patients begin with a relapsing- remitting (RRMS) course. Clinical relapse and new white matter lesion formation is dramatically reduced by current therapies. However, despite evidently efficacious treatment of RRMS, many patients eventually develop progressive MS (PMS) wherein disability accumulates refractory to treatment. Progressive disability is driven by neurodegeneration which begins early in the disease, occurs independent of relapses, and is poorly understood. Two potential contributors to neurodegeneration are subclinical inflammation and metabolic stress. Clinical relapses and new lesion formation are driven by inflammatory demyelination, but additional inflammation is present outside of discrete lesions. This inflammation is associated with chronic demyelination and increased metabolic demand. Both inflammation and metabolic stress may lead to neurodegeneration, either alone or in combination. This study will use a novel positron emission tomography (PET) imaging agent, 11C-CS1P1, which binds to sphingosine-1-phosphate-receptor 1 (S1PR1) as a marker of inflammation. S1PR1 signaling is critical to MS as evidenced by four FDA approved S1P-modulators with high efficacy for reducing relapses in RRMS. Additionally, we will use metabolic imaging with 18F-FDG PET and advanced, oxygen-sensitive magnetic resonance imaging (MRI) to measure cerebral glucose and oxygen utilization, respectively. These measurements will be made in a cohort of heathy control participants, RRMS patients who will be initiating an S1P-modulating drug and RRMS patients initiating a similarly efficacious non-S1P-modulating drug (B-cell depleting therapies). Patients will be imaged prior to and 3-months following initiation of treatment. These data will allow for testing the hypotheses that subclinical inflammation and metabolic stress are present in RRMS and are incompletely mitigated by current treatments. This study will address three Specific Aims. The first aim tests the hypothesis that inflammation is increased outside of MS lesions in seemingly normal appearing tissue and is reduced by S1P-modulation. The second aim will examine the metabolic needs and stress of normal appearing white matter and gray matter in MS patients compared to controls. The first two aims will compare their respective biomarkers pre- vs. post-initiation of an S1P-modualting drug. The final aim investigates how S1PR1 expression and metabolic stress are modulated by an efficacious, but not S1P-modualting therapy. Completion of this study will provide new understanding of processes that drive neurodegeneration in MS and contribute to clinical morbidity and disability. ## Key facts - **NIH application ID:** 10881978 - **Project number:** 5K23NS128325-02 - **Recipient organization:** WASHINGTON UNIVERSITY - **Principal Investigator:** Matthew Ryan Brier - **Activity code:** K23 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $232,918 - **Award type:** 5 - **Project period:** 2023-07-15 → 2028-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10881978 ## Citation > US National Institutes of Health, RePORTER application 10881978, PET and MRI Evaluation of Cerebral Inflammation and Metabolic Stress in Relapsing Multiple Sclerosis (5K23NS128325-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10881978. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*