Carotid Artery Plaque, Cognitive Impairment, Inflammation
Conditions
Keywords
Carotid artery, MRI, PET, Intraplaque hemorrhage
Brief summary
The invesigators propose a clinical study on patients undergoing carotid surgery (endarterectomy). The invesigators will determine carotid artery imaging features associated with (1) vessel wall inflammation, (2) downstream brain inflammation, and (3) cognitive benefit from surgery. This project will uncover links between inflamed carotid plaque and downstream brain inflammation. The invesigators will also determine carotid plaque imaging features predicting cognitive benefit from carotid surgery.
Detailed description
This research is directed at a major stroke source, the carotid artery, a major vessel that supplies blood to the brain. It has long been known that carotid narrowing is an important stroke risk factor. However, many patients with narrow carotids do not have strokes, and many patients with seemingly normal carotids have strokes. MRI research now suggests that the carotid wall itself is the stroke source. Using carotid MRI, clinicians can identify previously invisible markers of unstable carotid plaque, including carotid wall bleeds (intraplaque hemorrhage). The working hypothesis is that patients with these unstable carotid plaques may have higher inflammation in both their carotid arteries and brain. This inflammation has been implicated in other diseases, including dementia. Carotid wall bleeds can easily be seen with carotid MRI, but are often invisible on ultrasound and CT scans. By using MRI, the invesigators have found that this silent killer is an important stroke risk factor even without carotid narrowing. Now that imaging can detect carotid wall bleeds, where do the bleeds come from? Recent research points to inflammation within the carotid wall. The invesigators plan to use histology to detect this inflammation in the vessel wall. Another question is, does inflammation in the carotid wall lead to inflammation in the brain? Using PET scans, the invesigators plan to determine whether inflammation in the brain is linked to carotid disease. Lastly, the invesigators hope to find out if carotid wall inflammation contributes to memory loss and if surgery is beneficial in these patients. The invesigators hope to detect this inflammation in the vessel wall and brain before patients develop stroke, memory loss and dementia. This will be of huge benefit not only in the detection of diseases, but would also allow clinicians to monitor treatment effect on both carotid disease and brain inflammation. The invesigators also hope to use these tools to detect early treatment response. This research will accelerate the pace of future clinical trials to bring important new medications to patients sooner.
Interventions
DRUGImaging with flutemetamol F 18 PET/CT
All subjects will undergo diagnostic imaging as the intervention. This imaging will be with flutemetamol F 18 PET/CT
Sponsors
Scott Mcnally
American Heart Association
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
This is a diagnostic-interventional cohort study in patients undergoing carotid endarterectomy for atherosclerotic disease.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Patients ≥18 years old and plans for carotid endarterectomy.
Exclusion criteria
* Patients with carotid occlusion will be excluded, due to one carotid contributing to both right and left brain blood supply. * Other known sources of cardioembolism, including atrial fibrillation, mechanical heart valve, left atrial or ventricular thrombus or intracardiac mass, endocarditis, EF \<30% * Known stroke mimics including multiple sclerosis or brain tumor * MRI contraindications per ACR guidelines, including patients with pacemakers, renal failure with eGFR\<30 ml/min/1.73m2, and contrast allergy * \[18F\]Flutemetamol contraindications per manufacturer guidelines, including patients with prior reactions * Known stage IV malignancy * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Carotid intraplaque hemorrhage correlation with carotid plaque inflammation on immunohistochemistry. | baseline | Carotid plaque inflammation will be calculated with quantitative immunohistochemistry and correlated with intraplaque hemorrhage while controlling for confounders. |
| Carotid MRI-detected intraplaque hemorrhage and prediction of brain inflammation on PET/CT. | baseline | Outcome 2. The primary outcome, brain inflammation will be compared in carotid intraplaque hemorrhage positive and negative sides, controlling for confounders including stenosis and perfusion. |
| Preoperative MRI-detected carotid intraplaque hemorrhage and prediction of cognitive improvement after endarterectomy. | Change from baseline at 3 month followup | Outcome 3. The primary outcome, difference in cognitive score will be compared in carotid intraplaque hemorrhage positive and negative patients, controlling for stenosis, perfusion and ischemic symptoms. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoseph S McNally, MD, PhD
University of Utah
Outcome results
None listed