In 2012 Thomas S. Hatsukami, MD, Professor of Surgery, Division of Vascular Surgery at the University of Washington in Seattle, was presented the first Multicenter Clinical Studies Planning Grant. This $100,000 grant was presented to fund a high-impact multicenter clinical study in the treatment and/or prevention of vascular disease. The following is an update on Dr. Hatsukami’s clinical study.

Each year, more than 100,000 carotid endarterectomy (CEA) and carotid stenting (CAS) procedures are performed in the United States alone. Increasingly, the value of CEA and CAS in patients with asymptomatic carotid atherosclerosis is debated. Randomized trials comparing CEA to medical therapy in patients with asymptomatic carotid stenosis have shown that the absolute reduction in risk for stroke provided by surgical intervention is relatively small. Given further progress in the medical management of atherosclerosis, some providers now exclusively recommend non-surgical treatment to their patients with asymptomatic carotid disease.

Figure 1: Simultaneous Non-contrast Angiography and intra-Plaque hemorrhage (SNAP) image of the carotid artery. Panel (a) demonstrates a 3D maximal intensity projection (MIP) image of the non-contrast enhanced angiography acquisition. There is a high-grade stenosis in the proximal external carotid artery (arrowhead) and a minimally obstructive, ulcerated plaque in the proximal internal carotid artery (arrow). The simultaneously acquired IPH image shown in panel (b) is then color coded and fused with the angiographic data in panel (c). Axial reformatted images (d) demonstrate the ulcer (arrows) and surrounding high signal intensity consistent with intraplaque hemorrhage, confirmed by the corresponding matched histology cross-sections (Mason's trichrome).

To deny carotid surgery or stenting to all such patients, however, may subject a subgroup of these individuals to the devastating consequences of stroke – the leading cause of major long term disability and fourth leading cause of death in the United States. To improve the selection of individuals for CEA and CAS, better methods for identifying the high risk carotid plaque are needed.

A number of studies have shown that patients with intraplaque hemorrhage (IPH) or a disrupted luminal surface (DLS), as identified by carotid magnetic resonance imaging (MRI), have a five to 17-fold higher risk for future transient ischemic attack (TIA) or stroke.

While results from these cohort studies are promising, a randomized controlled trial is needed to determine whether plaque characterization with MRI improves the selection of appropriate candidates for carotid endarterectomy or stenting. In preparation for such a trial, there are a number of barriers that must first be addressed, including standardization of MR image acquisition protocols and assurance of uniformity in image quality and reproducibility across imaging platforms and study centers.

There also is a need to reduce the time for image acquisition, which would decrease study costs and improve subjects’ tolerance of the scan. Furthermore, protocols that avoid the use of gadolinium contrast would permit assessment of patients with renal insufficiency. Finally, quantitative analysis tools that improve the efficiency and reliability of interpretation of large volumes of imaging data are essential.

With funding from the SVS Foundation Multicenter Clinical Studies Planning Grant, a network of imaging centers has been established across North America.

Over the past year, investigators from institutions in this network have collaborated on the development and testing of rapid, high-resolution 3-D MR imaging protocols capable of identifying IPH, luminal surface disruption, carotid arterial remodeling and luminal stenosis without the need for intravenous contrast (Figure 1, on page 7).

This work provided critical preliminary background data for an application to the NIH for a multicenter study of asymptomatic carotid disease using these state-of-the art MRI techniques. Furthermore, this work has set the stage for additional multicenter grant applications planned for the coming year that will involve investigators in North America, Europe, and Asia.

Clinical Relevance

The current paradigm for the management of carotid atherosclerosis is guided by severity of stenosis. With high-resolution carotid MRI, we now have the opportunity to shift the focus from the flow channel to the diseased arterial wall itself.

Given the heterogeneity of carotid plaque types, a method that can reliably characterize the carotid atheroma in vivo may lead to improved risk stratification for new or recurrent stroke.

Better selection criteria will lead to a reduction in overall health care costs by reserving surgical procedures for individuals at greatest risk for future stroke. Furthermore, a better understanding of the nature of the vulnerable plaque will serve as a foundation for further research into the mechanisms of initiation and progression toward development of high-risk lesions of atherosclerosis, and perhaps lead to development of novel pharmacological therapy.

The investigators wish to express their sincere gratitude to the SVS Foundation, whose support has significantly accelerated progress toward a better understanding of the high-risk carotid plaque.

Progress Report on SVS Foundation Multicenter Clinical Studies Planning Grant