Smoldering Inflammation in MS

Inclusion Criteria:

* Male or female, any race
* Age ≥ 18 years
* Capable of providing written informed consent for volunteering to undergo research procedures
* Diagnosis of MS as established by the referring physician and confirmed by the Sponsor-Investigator. Only patients with active disease, defined as at least 1 enhancing lesion present in the preceding 6 months, will be enrolled
* Treatment naïve except for relapse-related treatments such as corticosteroids or plasmapheresis,
* Planned initiation, at the discretion of the referring physician, of a high efficacy DMT. High efficacy DMT will be defined to include ocrelizumab, natalizumab, or any MS treatment in the opinion of the Sponsor-Investigator to have similar efficacy as the named treatments
* Clinical labs, including at least a CBC and BMP, without significant abnormality as determined by the Sponsor-Investigator or designee, within the 3 months prior to enrollment

Exclusion Criteria:

* Presence of a low binding polymorphism for TSPO
* Hypersensitivity to \[11C\]-CS1P1, \[11C\]-DPA-713, \[18F\]-FDG, or any of their excipients
* Contraindications to PET, CT or MRI (e.g. certain incompatible electronic medical devices, inability to lie still for extended periods) that make it potentially unsafe for the individual to participate
* eGFR less than 60 (for gadolinium)
* Severe claustrophobia
* Women who are currently pregnant or breast-feeding
* Currently undergoing radiation therapy
* Insulin dependent diabetes
* Contraindication to lumbar puncture (LP), including use of antiplatelet therapy (other than aspirin 81mg), therapeutic anticoagulation, or space occupying intracranial mass. History of a coagulopathy is also exclusionary
* Any condition that, in the opinion of the Sponsor-Investigator or designee could increase risk to the participant, limit the participant's ability to tolerate the research procedures or interfere with collection of the data (e.g., renal or liver failure, advanced cancer)
* Current or recent (within 12 months prior to screening) participation in research studies involving radioactive agents such that the total research-related radiation dose to the participant in any given year would exceed 5 rem