Cerebrovascular disease is a major source of neural injury and there is an urgent need for comprehensive evaluation of these patients. High-resolution MRI (HR-MRI) allows direct visualization of intracranial vessel wall pathology in the setting of acute ischemic stroke and intracranial aneurysm (intracranial aneurysm rupture.Vessel wall enhancement on HR-MRI results from inflammation and has considerable potential as a marker of future stroke risk or aneurysm rupture. We will use our HR-MRIvwMRI protocol and other techniques of measuring plaque and aneurysms vulnerability, including laboratory markers of abnormal inflammation and oxidization, which have been shown to correlate with vulnerable carotid atherosclerosis and intracranial aneurysms, but have not been studied in symptomatic ICAS or IA.The unmet need is a study validating HR-MRI reliability and the association of vessel-wall enhancement with both symptomatic and pro-inflammatory status in patients with cerebrovascular disease.
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. All 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 hour post- using ferumoxytol contrast infusion. Study MRI #3 is a follow-up vessel wall MRI with gadolinium in 1 year.The investigator(s) will analyze two groups of participants 60 with intracranial atherosclerosis and 20 with intracranial aneurysms.
- Ferumoxytol Injectable Product Drug
Other Names: Feraheme Intervention Desc: Patients will be administered a single dose of ferumoxytol as an MRI contrast ARM 1: Kind: Experimental Label: 1 Description: 10 patients with symptomatic intracranial atherosclerosis ARM 2: Kind: Experimental Label: 2 Description: 10 patients with asymptomatic intracranial atherosclerosis ARM 3: Kind: Experimental Label: 3 Description: 10 patients with symptomatic intracranial aneurysm ARM 4: Kind: Experimental Label: 4 Description: 10 patients with asymptomatic intracranial aneurysm
|Type||Measure||Time Frame||Safety Issue|
|Primary||Vessel Wall Enhancement with Gadolinium compared to Vessel Wall Enhancement with Ferumoxytol in intracranial atherosclerosis and intracranial aneurysm groups||4 days|