Stroke Prevention and Therapy

4:00PM Patient Selection for Novel Stroke Therapy Using Advance Imaging
Michael H. Lev, MD, Director, Emergency Neuroradiology and Neurovascular Lab, Massachusetts General Hospital; Associate Professor of Radiology, Harvard Medical School, mlev@partners.org
Moderator: David B. Hackney, MD, Professor of Radiology, Harvard Medical School, Assistant Dean for Faculty Development, Harvard Medical School, Department of Radiology, Beth Israel Deaconess Medical Center, dhackney@bidmc.harvard.edu

There are approximately 750,000 stroke patients per year in the United States. Only 3-5% of these people are treated with intravenous tissue plasminogen activator (IV- tPA), the only FDA-approved medical treatment for acute non-hemorrhagic stroke. According to current guidelines, IV-tPA must be given within three hours of stroke onset. Michael Lev of Harvard Medical School, however, suggests that some patients could benefit from IV-tPA even if they were treated beyond the three-hour time window.

The etiology of stroke is due to vascular injury that is either hemorrhagic (15% of cases) or ischemic (85% of cases) in nature. When a patient comes to the hospital suffering from an acute stroke, unenhanced computed tomography (CT) is performed to exclude the possibility of bleeding in the brain. If there is no evidence of bleeding, then the patient is a candidate for IV-tPA. Traditionally, doctors have treated stroke patients according to the adage, “Time is brain.” Lev proposes a more nuanced way of treating patients, and he suggests the adage, “Mismatch is brain.” He advocates using advanced magnetic resonance imaging (MRI) or CT imaging to determine how much of the brain is already dead at admission and how much of the brain is at risk of dying if there is no reperfusion. According to these selection criteria, patients with little dead tissue and a lot of at-risk tissue would be candidates to receive IV-tPA reperfusion therapy, even more than three hours after stroke onset.

The mismatch between dead and dying tissue is being used as a patient selection tool in a Phase Two trial of desmotoplase, a clot-busting drug. Lev attributes some promising results obtained in this study to the new method of patient selection.

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5:00PM New Perspectives in the Imaging of Carotid Artery Plaque
Javier Romero, MD, Director, Ultrasound; Associate Director, Neurovascular Laboratory; Staff Radiologist, Neuroradiology; Staff Radiologist, Pediatric Radiology, Massachusetts General Hospital; Instructor Radiology, Harvard Medical School, rmromero@partners.org
Moderator: Rajiv Gupta, MD, Cardiac and Neuro Radiologist, Massachusetts General Hospital, rgupta1@partners.org

Carotid artery plaque raises one’s risk of stroke, but not all plaque is equally dangerous. Vulnerable plaque can lead to thrombosis (clotting of the artery) or to the formation of emboli (small clots) that travel to the brain. The pathogenesis of stroke is ischemic, or the result of plaque, in approximately 83% of cases. Studies have shown that fifty asymptomatic patients with carotid artery stenosis (narrowing) of greater than 70% undergo carotid endarterectomy (CEA), a plaque-removing procedure, to prevent one stroke, for three years of follow-up. In asymptomatic patients with carotid artery stenosis of 50-70%, the benefit of CEA is less well understood. In the future, imaging techniques could help doctors predict which people with intermediate levels of stenosis will benefit most from surgery.

Multiple techniques exist to assess unstable plaque. These include ultrasound, angiography, magnetic resonance imaging (MRI), computed tomography (CT), computerized tomographic angiography (CTA), positron emission tomography (PET), and biochemical assays. A large study utilizing ultrasound found that the presence of hypoechoic (non-calcified) plaque and greater than 50% stenosis is connected to increased stroke risk while hyperechoic (calcified) plaque is more stable. Interestingly, in coronary artery disease, highly calcified plaque is associated with a high risk of symptoms while in carotid artery disease, highly calcified plaque is associated with a low risk of symptoms. Studies using MRI have found that the presence of plaques with thin fibrous caps is correlated with symptoms of transient ischemic attack (TIA) and stroke. Biochemical studies done in rabbits fed high cholesterol diets have shown that the enzyme myeloperoxidase, which activated macrophages and neutrophils secrete in response to inflammation, is also secreted by vulnerable plaque prone to rupture.

The lab of Javier Romero is studying the ability of CTA to provide information about plaque vulnerability. Patients with enhancement on CTA of the vasa vasorum (a network of small arterioles, capilllaries, and venules that supply the outer tissues of large blood vessels) at the carotid bifurcation appear more likely to be symptomatic. Romero’s group also compared symptomatic and asymptomatic patients and found that the asymptomatic patients had denser, more calcified plaques than symptomatic patients, a finding that corroborates previous ultrasound data. Plaque density may be a surrogate marker of plaque stability and a potential way to determine whether an asymptomatic patient with carotid artery stenosis should undergo surgical treatment.

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