Treatment Targets for Inflamed Intracranial Atherosclerosis on Vessel Wall MRI

Intracranial atherosclerosis accounts for 10 to 40%, depending on ethnicity, of the 700,000
ischemic strokes in the United States every year.The annual rate of recurrent stroke in
patients with optimally treated Intracranial atherosclerosis remains more than twice the
average of other stroke etiologies (12.5% vs. 5%).Intracranial aneurysm ruptured affects up
to 30,000 Americans every year and 50% of patients die within a month of intracranial
aneurysm rupture.7 A robust literature has established that vessel wall MRI of extracranial
carotid vessel wall enhancement can predict stroke, independent of stenosis. Vessel wall
enhancement has been reported in symptomatic Intracranial atherosclerosis and intracranial
aneurysm but the role of local and systemic inflammation is unknown. Inflammatory biomarkers
are elevated in symptomatic extracranial atherosclerosis and in unstable intracranial
aneurysm, but the association with vessel wall MRI findings in Intracranial atherosclerosis
and intracranial aneurysm has not yet been explored.Vessel wall enhancement is typically
demonstrated by the uptake of gadolinium MRI contrast into the aneurysm wall or
atherosclerotic plaque. A novel MRI contrast agent, ferumoxytol, allows multicontrast
weighting on T1w and T2w images and provides important insight into the role of local vessel
wall inflammation by accumulating in macrophages on delayed T2* sequences.

To identify effective prevention and treatment strategies for cerebrovascular disease, the
investigator(s) need to critically evaluate vessel wall MRI techniques, determine vessel wall
enhancement prevalence, and explore the link between vessel wall enhancement and
inflammation. The investigator(s) hypothesize that vessel wall enhancement is reliable,
associated with symptomatic Intracranial atherosclerosis/intracranial aneurysm and higher
levels of inflammatory biomarkers. In order to answer our hypotheses, the investigator(s)
propose a pilot study on 80 participants. The investigator(s) will opportunistically enroll
participants who receive standard of care vessel wall MRI with gadolinium contrast or perform
a baseline vessel wall MRI with gadolinium if needed. Intracranial atherosclerosis
participants will have a total of 2-3 study vessel wall MRIs. Study MRI #1 will be performed
with gadolinium, if a standard of care MRI has not already been performed. Study MRI #2 will
be performed 72-78 hours post- using ferumoxytol contrast infusion. Study MRI #3 is a
follow-up vessel wall MRI with gadolinium in 1 year. Intracranial aneurysm participants will
have 1-2 MRIs depending on if they have already had a baseline MRI.Study MRI #2 will be
performed 72-78 hours post- using ferumoxytol contrast infusion. The investigator(s) will
analyze two groups of participants 60 with intracranial atherosclerosis and 20 with
intracranial aneurysms.

80 patients will be enrolled in this prospective cross-sectional study of 2 cohorts:(A)
Intracranial atherosclerosis & (B) Intracranial aneurysms

- Inclusion Criteria:

- (A) cohort: 60 intracranial atherosclerosis (stenosis less than 25%)

- recent ischemic stroke (less than or equal to 14 days)

- (B) cohort: 20 intracranial aneurysms patients participants:

- 10 asymptomatic

- 10 with recent intracranial aneurysm(s) rupture (less than or equal to 7
days).

- Exclusion Criteria:

- Less than 18 years old

- Documented history of atrial fibrillation (for intracranial atherosclerosis
cohort).

- Carotid stenosis greater than 70% (for intracranial atherosclerosis cohort).

- Pregnant women

- Contrast allergy

- Acute or chronic kidney disease with glomerular filtration rate<30 ml/min/1.73m2

- Intravenous iron sensitivity

- Serum ferritin and transferrin saturation above age-adjusted upper limit of
normal. If serum ferritin is above normal, but transferrin saturation is normal,
the patient is not excluded.

- Pacemaker or other MRI contraindications