Treatment Targets for Inflamed Intracranial Atherosclerosis on Vessel Wall MRI
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 60 patients with intracranial atherosclerosis |
Drug: Ferumoxytol Injectable Product
Patients will be administered a single dose of ferumoxytol as an MRI contrast
Other Names:
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| Experimental: 2 20 patients with intracranial aneurysm |
Drug: Ferumoxytol Injectable Product
Patients will be administered a single dose of ferumoxytol as an MRI contrast
Other Names:
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Outcome Measures
Primary Outcome Measures
- Vessel Wall Enhancement with Gadolinium compared to Vessel Wall Enhancement with Ferumoxytol in intracranial atherosclerosis (ICAS) group. [1 year]
Both patient groups will have a high-resolution vessel wall enhancement-gadolinium MRI at baseline with a delayed high-resolution vessel wall enhancement-Ferumoxytol MRI. Prevalence will be analyzed between the different participants in each group. Hypothesis: Participants with intracranial atherosclerosis will have a high prevalence of vessel wall enhancement.
- Vessel Wall Enhancement with Gadolinium compared to Vessel Wall Enhancement with Ferumoxytol in intracranial aneurysm (IA) group [4 days]
Both patient groups will have a high-resolution vessel wall enhancement-gadolinium MRI at baseline with a delayed high-resolution vessel wall enhancement-Ferumoxytol MRI. Prevalence will be compared between the asymptomatic and symptomatic participants in each group. Hypothesis: Participants with symptomatic intracranial aneurysm will have a higher prevalence of vessel wall enhancement than asymptomatic participants.
Eligibility Criteria
Criteria
80 patients will be enrolled in this prospective cross-sectional study of 2 cohorts:(A) Intracranial atherosclerosis & (B) Intracranial aneurysms
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Inclusion Criteria:
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(A) cohort: 60 intracranial atherosclerosis (stenosis less than 25%)
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recent ischemic stroke (less than or equal to 14 days)
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(B) cohort: 20 intracranial aneurysms patients participants:
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10 asymptomatic
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10 with recent intracranial aneurysm(s) rupture (less than or equal to 7 days).
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Exclusion Criteria:
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Less than 18 years old
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Documented history of atrial fibrillation (for intracranial atherosclerosis cohort).
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Carotid stenosis greater than 70% (for intracranial atherosclerosis cohort).
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Pregnant women
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Contrast allergy
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Acute or chronic kidney disease with glomerular filtration rate<30 ml/min/1.73m2
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Intravenous iron sensitivity
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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.
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Pacemaker or other MRI contraindications
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale University | New Haven | Connecticut | United States | 06510 |
Sponsors and Collaborators
- Yale University
Investigators
- Principal Investigator: Adam de Havenon, MD, University of Utah
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB 00093870