High-Field MRI Iron-Based Contrast-Enhanced Characterization of Multiple Sclerosis and Demyelinating Diseases

7T MRI Ferumoxytol-Enhanced Characterization of Multiple Sclerosis and Demyelinating Diseases

Feraheme (ferumoxytol) is FDA-approved for iron supplementation and is composed of iron oxide nanoparticles classified among the ultra-small superparamagnetic iron oxides (USPIO). In this project we hypothesize that Feraheme could become a sensitive and specific marker of active inflammation in multiple sclerosis. We will explore this hypothesis taking advantage of ultra high field strength (7T) MRI to further increase the effectiveness of the contrast agent Feraheme at revealing inflammatory activity.

Multiple sclerosis (MS) is a neurological disorder that affects young adults world-wide. Feraheme (ferumoxytol) is FDA-approved for iron supplementation and is composed of iron oxide nanoparticles classified among the ultra-small superparamagnetic iron oxides (USPIO). After IV injection, the particles are taken up by the monocyte-macrophage system and can also be used to track macrophage infiltration by magnetic resonance imaging (MRI) after systemic injection owing to the strong image contrast of the iron-loaded macrophages. Approximately 24 hours after their IV injection, free particles are cleared from the circulation and MR signal alterations are thought to arise from the capture of particles by circulating phagocytic cells that are attracted to inflammatory lesions.

In this project we hypothesize that Feraheme could become a sensitive and specific marker of active inflammation in multiple sclerosis. We will explore this hypothesis by taking advantage of ultra high field strength (7T) MRI to further increase the effectiveness of the contrast agent Feraheme at revealing inflammatory activity.

Inclusion Criteria:

• Patients will be included if they are at least 18 years old and meet the revised diagnostic criteria for multiple sclerosis, relapsing remitting type.
• Patients will be included based on MR evidence of disease activity after Gadolinium (enhanced lesion) on a previous screening MR in the previous 3 weeks days before Feraheme administration.

Exclusion Criteria:

• Children (age < 18)
• Those who lack decision-making capability
• Contraindication to MRI such as pacemaker, other MR-incompatible metal implants or claustrophobia
• Known allergy to dextran or drugs containing iron salts or any previous history of severe allergic reactions
• Evidence of iron overload such as hemochromatosis or other hematologic disorders that imply iron level superior to the normal level.
• Pregnancy or breast feeding.
• History of renal disease or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) <40ml/min/1.73m?