MR, Histologic And EM Imaging Of Intravenous Ferumoxytol In Central Nervous System (CNS) Inflammation

Subjects are recruited as patients in one of the neurology, neurosurgery, neuro-oncology,
Multiple Sclerosis Clinic or cardiothoracic surgery clinics at OHSU. Eligible subjects will
be enrolled in different groups based on their disease (MS, cardiac surgery or CNS vascular
surgery, stroke). Subsequently a MRI and MRA of the brain using the standard contrast agent
(Gadolinium) will be obtained; this study will be compared with the ferumoxytol-contrasted
MRA and MRIs performed the next day(s).

Visit 1: the subjects are enrolled and distributed in their corresponding group; also basic
laboratory studies are obtained as well as a Gadolinium contrasted MRI and MRA of the brain.

For Groups 1 and 2 (MS and Stroke):

Visit 2: Ferumoxytol will be injected as an i.v. bolus. The total dose over 2 hours will not
exceed 510mg, and can be divided into multiple smaller doses such as 1 mg Fe/kg to optimize
MRA imaging and may be diluted up to 4 fold in normal saline to reduce T2* effects in the MR
angiography.

Visit 3: 24 hours after the second visit an MRI with the standard contrast agent will be
done.

Last visit: 1 month after Ferumoxytol administration, the subject will be reassessed with
physical and laboratory exams.

For Groups 3 and 4 (Cardiac surgery or CNS vascular surgery):

After the screening visit (Visit 1) and baseline MRI and MRA you will be randomly assigned
to one of two groups. These groups are very similar but there are slight differences in the
schedule of events.

- Group 3a and 4a: ferumoxytol infusion (Visit 2) before surgery

- Group 3b and 4b: ferumoxytol infusion (Visit 2) after surgery

Visit 2: Ferumoxytol will be injected as an i.v. bolus. The total dose over 2 hours will not
exceed 510mg, and can be divided into multiple smaller doses such as 1 mg Fe/kg to optimize
MRA imaging and may be diluted up to 4 fold in normal saline to reduce T2* effects in the MR
angiography.

Visit 3: 24-72 hours after the second visit an MRI with the standard contrast agent will be
done.

Last visit: 1 month after Ferumoxytol administration, the subject will be reassessed with
physical and laboratory exams.

Inclusion Criteria:

- Subjects must have a clinical, radiological or established histological diagnosis of
multiple sclerosis, stroke, or be requiring cardiac or CNS vascular surgery. Subjects
with a CNS inflammatory lesion that is suspicious for neoplasm or radiation induced
inflammation (vasculitis) will also be included (group 1a). McDonald's criteria will
be used for the diagnosis of multiple sclerosis.

- Subjects must be 18 years or older

- Subjects will be followed for at least 1 month after the infusion of ferumoxytol.

- All subjects or their authorized representative must sign a written informed consent
and give HIPAA authorization in accordance with institutional guidelines.

- Female subjects of child-bearing potential must be postmenopausal, surgically
sterile, or using a reliable form of contraception for at least a month. These
criteria can be waved at the discretion of the investigator if the one-month wait
required is not in the best interest of the patient.

- Karnofsky must be 30% or greater

Exclusion Criteria:

- Subjects with clinically significant signs of uncal herniation

- Subjects who have a contraindication for MRI: metal in their bodies (a cardiac
pacemaker or other incompatible device), are severely agitated, or have an allergy to
Gd contrast material.

- Subjects with known allergic or hypersensitivity reactions to parenteral iron,
parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide
preparations

- Subjects with known hepatic insufficiency or cirrhosis

- Subjects with known or suspected iron overload

- HIV-positive subjects on combination anti-retroviral therapy are ineligible because
of the potential for pharmacokinetic interactions with ferumoxytol

- Pregnant or lactating women are excluded from this study because of possible risk to
the fetus or infant.