Standardization of Stroke Perfusion-CT for Reperfusion Therapy

The goal of the SSPERT project is to harmonize the perfusion software packages available in the stroke community so that they can be safely used to select stroke patients for acute reperfusion therapy, either as part of a clinical trial or the clinical practice.

At the end of the SSPERT project, the harmonization of the perfusion software packages will be such that any stroke patient, scanned on any type of CT or MR scanner, with the data processed on any type of post-processing package, will be diagnosed with similar values (within a certain range fi-om each other) in terms of the volumes of infarct core and of penumbra, so that the same treatment decision is made independent of the type of scanner and post-processing package.

This project will set the stage for one or more clinical trials using any of the "STIR perfusion-CT software packages to select acute ischemic patients for reperfusion therapy in an extended time window (beyond 3-4.5 hours) or for selecting wake-up stroke patients for reperfusion therapy.

CAPRISK Study - CArotid Plaque imaging to PRedict Ischemic StroKe

Carotid artery disease is common in the general population (75% in men and 65% in women >64). Clinical management of patients with a degree of carotid stenosis >70% is well established. However, in a large majority of cases (>90% of cases), carotid stenosis is <70%. While <70% carotid stenosis is associated with a low individual risk of ischemic stroke (1.3% to 3.3% annually), its high prevalence in the general population translates into a large number of ischemic strokes on a population level. In these patients with <70% carotid stenosis, the exact degree of luminal narrowing fails to predict the associated risk of stroke. Recently, a concept has emerged that direct assessment of the atherosclerotic process within the carotid wall would be a better predictor of the risk of stroke than characterizing its indirect impact on the adjacent lumen – an approach that is made possible by the ability of imaging techniques, such as ultrasound, MRI, and CT, to assess the carotid artery wall in addition to the lumen.

The goal of this research is to identify a carotid artery wall feature (or a combination thereof) that would allow differentiation in patients with <70% carotid stenosis between those at high risk and those at low risk of ischemic stroke. In pursuit of this goal, we propose to conduct a nested study in a retrospective cohort of patients from our institution who had a CT-angiogram of their carotid arteries between 2001 and 2007 (n=4,891). We will compare and evaluate 6 carotid artery wall features (maximal carotid wall thickness, carotid plaque ulcerations, thickness of the fibrous cap, lipid-rich necrotic core, intraplaque hemorrhage, calcifications). The primary outcome will be ischemic strokes of carotid origin. We propose 3 specific aims, which will test the 3 following hypotheses, with specific attention paid to patients with <70% carotid stenosis:

Aim 1: To test the hypothesis that a combination of one or several among 6 carotid artery wall features discriminates carotid stroke patients from non-carotid stroke patients.

Aim 2: To test the hypothesis that a combination of one or several among 6 carotid artery wall features discriminates the side ipsilateral to the stroke from the contralateral side in carotid stroke patients.

Aim 3: Among patients free of stroke at baseline, to test the hypothesis that a combination of one or several among 6 carotid artery wall features predicts incident carotid ischemic stroke during follow-up.

This project is supported by a grant from the Dana Foundation
(http://www.dana.org/grants/imaging/detail.aspx?id=12982)

VIPs study - Vascular Effects of Infection in Pediatric Stroke

Stroke is becoming more recognized as a cause of childhood disability.¹ It is estimated that there are 2.3 to 13 children with strokes per 100,000 children annually;^2-5 and for strokes in newborns less than a month old, there are close to 1 per 4,000 live births.⁶ Historically, it has been thought that children recover well from stroke but this has been contradicted by recent studies documenting a high rate of life-long sickness, disability, or poor health.^6-8 Thus, although childhood stroke is rare, the disabling long-term conditions it causes usually result in a larger burden on society than previously thought.

Despite this increasing recognition of the importance of childhood stroke, there is little quality data about this disease.  While strategies for preventing strokes in adults have been studied extensively, the same data for children are limited.  Sickle cell disease is the one exception; the use of blood transfusions to prevent primary stroke in high risk children with this disease has been well documented.⁹ Outside of this setting, there are no proven means of stroke prevention in children.  The development of stroke prevention strategies depends on a good understanding of the how the disease works, but this is also not well understood.

Infection may cause stroke which causes the body to be more likely to form blood clots. Despite this, it may also cause a disease of the arteries in the head by either the infection directly invading blood vessel walls or injury to cells from the body’s own response to the infection. Children are the best group of people to study the effects of infection on blood vessel because the additional factors that come with age are not present. Recent studies show that children with strokes and diseased arteries have a large chance of having repeated strokes. Most of these artery diseases are dissection and moyamoya, but most of these children have a narrowing of vessels going to one side of the brain. The cause of this is not clear, but infectious agents like the herpes viruses might play a role.

The VIPS study is a multicenter observational study of childhood stroke to test the hypothesis that infection can lead to arterial ischemic stroke, also known as AIS, by causing vascular injury, and the resultant arteriopathy predisposes children to recurrent stroke

Dr. Wintermark and his team serve as neuroimaging core lab for this study.

This project is supported by a grant from NINDS.

MR- Guided focused Ultrasound

MRI-guided focused ultrasound surgery is a noninvasive thermal ablation method that uses magnetic resonance imaging (MRI) for target definition, treatment planning, and closed-loop control of energy deposition. Integrating FUS and MRI as a therapy delivery system allows us to localize, target, and monitor in real time, and thus to ablate targeted tissue without damaging normal structures.

Dr. Wintermark is interested in applying MR-guided focused ultrasound to patients with stroke or other cerebrovascular conditions. He is also interested in modulating the blood-brain barrier using Mr-guided focused ultrasound, in order to allow for focal and targeted drug delivery.