This pilot study takes the innovative approach of using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle enhanced MRI to measure activity of the innate immune system within MS lesions. Activity of innate immunity has been hypothesized as one of the critical pathologic processes underpinning neurologic worsening in progressive MS. As such, in the short term this project proposes to investigate USPIO uptake in SPMS lesions as a promising in vivo imaging biomarker for chronic-active lesions, as distinguished from chronic-inactive lesions.

Inclusion Criteria:

1. Adults age 35 to 65 years
2. Clinically diagnosed with secondary progressive multiple sclerosis (SPMS) (2017 McDonald Criteria)
3. Worsening 25 foot walk time (worsening SPMS cohort) over the preceding 2 years.
4. Ambulatory with ability to walk at least 20 meters without rest, with or without aid
5. Ability and willingness to attend study visits and complete the study

Exclusion Criteria:

1. Clinically diagnosed with relapsing remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS), clinical isolated syndrome (CIS), or radiologically isolated syndrome (RIS)
2. Clinical MS relapse and/or new MRI lesion(s) within the preceding 2 years
3. Positive pregnancy test
4. Gadolinium contrast allergy
5. Acute or chronic kidney disease with eGFR <30 ml/min/1.73m2
6. Pacemaker or other MRI contraindications per American College of Radiology guidelines
7. Intravenous iron sensitivity
8. Serum ferritin and transferrin saturation above age-adjusted upper limit of normal (if serum ferritin is above normal, but transferrin saturation is normal, the subject is NOT excluded)