Treatment Targets for Inflamed Intracranial Atherosclerosis on Vessel Wall MRI

Overview

Intracranial atherosclerosis (ICAS) 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 ICAS remains more than twice the average of other stroke etiologies (12.5% vs. 5). A robust literature has established that vessel wall magnetic resonance imaging (vwMRI) of extracranial carotid vessel wall enhancement (VWE) can predict stroke, independent of stenosis. VWE has been reported in symptomatic ICAS, but the role of local and systemic inflammation is unknown. Inflammatory biomarkers are elevated in symptomatic extracranial atherosclerosis, but the association with vwMRI findings in ICAS has not yet been explored. VWE is typically demonstrated by the uptake of gadolinium MRI contrast into the aneurysm wall or atherosclerotic plaque. A novel MRI contrast agent, ferumoxytol, allows multi-contrast 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, we need to critically evaluate vwMRI techniques, determine VWE prevalence, and explore the link between VWE and inflammation.

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%).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. Vessel wall enhancement is typically demonstrated by the uptake of gadolinium MRI contrast into the 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. 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.