Ischaemic stroke is a major cause of death and disability worldwide. In patients with recent stroke, the 18F-fluoride positron emission tomography-computed tomography highlights high-risk culprit carotid plaque and is more discriminatory than 18F-fluorodeoxyglucose. Using hybrid positron emission tomography-magnetic resonance imaging investigators propose to build upon these findings by prospectively assessing 18F-fluoride uptake in a broad range of patients with acute transient ischaemic attack or ischaemic stroke. Investigators will specifically examine the association of 18F-fluoride uptake with multiparametric magnetic resonance imaging assessments of atherosclerotic plaque, especially the role of thrombus and lipid. Finally, using transcranial Doppler and diffusion-weighted magnetic resonance brain imaging, an assessment of the functional consequences of 18F-fluoride-positive atherosclerotic plaque will be performed. If successful, this technique has a number of valuable translational applications including the better selection of patients for carotid intervention.
The ability to identify the culprit carotid plaque represents a key goal in carotid artery imaging. Although an array of non-invasive imaging techniques can detect a wide spectrum of complementary high-risk characteristics, no single modality can reliably identify vulnerable plaques associated with future stroke development. Substantial histological data suggests that specific plaque components identify patients at high-risk for future ipsilateral stroke and cardiovascular events. This implies that investigators need to look beyond the traditional paradigm where the basis for carotid endarterectomy were formulated by an invasive imaging modality that provided no information on the arterial wall composition. Alternative imaging strategies are therefore required targeting not only in vivo carotid morphology but also plaque biology and disease activity. This is fundamental to optimal risk-stratification and appropriate selection of patients for high-risk vascular intervention. One new approach is to use non-invasive molecular imaging targeted at plaque biology using hybrid systems such as positron emission tomography-magnetic resonance imaging.
- CEA Procedure
Intervention Desc: Carotid Endarterectomy ARM 1: Kind: Experimental Label: Carotid Endarterectomy Description: Patients who are scheduled to undergo carotid endarterectomy for symptomatic carotid artery stenosis (≥50% by NASCET criteria for men, ≥70% for women) who are above 40 years of age.
- Transcranial doppler Diagnostic Test
Intervention Desc: Microembolic Signals detection ARM 1: Kind: Experimental Label: Carotid Endarterectomy Description: Patients who are scheduled to undergo carotid endarterectomy for symptomatic carotid artery stenosis (≥50% by NASCET criteria for men, ≥70% for women) who are above 40 years of age.
- 18F PET-MRI Radiation
Intervention Desc: 18F-fluoride Hybrid PET-MRI ARM 1: Kind: Experimental Label: Carotid Endarterectomy Description: Patients who are scheduled to undergo carotid endarterectomy for symptomatic carotid artery stenosis (≥50% by NASCET criteria for men, ≥70% for women) who are above 40 years of age.
Patients with evidence of an acute stroke, transient ischaemic attack or amaurosis fugax will be recruited as early as possible, but within 14 days of symptom onset. All patients will undergo careful clinical evaluation including carotid Doppler ultrasound assessment and magnetic resonance imaging of the brain. This cohort will be identified at the point they are referred to a vascular surgeon at Edinburgh Royal Infirmary.
|Type||Measure||Time Frame||Safety Issue|
|Primary||18F-fluoride uptake in the culprit plaque in carotid, aortic and intra-cranial vessels.||2 weeks|
Biospecimen Retention:Samples Without DNA - At the time of carotid endarterectomy, which is an established surgical intervention aimed at reducing the future risk of stroke in symptomatic patients, tissue will be collected, and lesion integrity and geometry will be preserved as much as possible. Specimens will be photographed in detail to permit subsequent assessment by independent and blinded reviewers. The excised tissue will be aligned and labelled to permit orientation in the carotid artery axis before undertaking 7.4 T magnetic resonance spectroscopy. Subsequently, carotid plaque will be snap frozen in liquid nitrogen. Cellular content, macrophage infiltration, apoptosis, and calcification-associated molecules within the plaques will be assessed by RNA analysis, immunohistochemistry and immunofluorescence using a variety of validated markers.