Novel Visualization Methods of Microvasculature in Stroke Patients

Novel Visualization Methods of Microvasculature in Stroke Patients

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By Dr. Andrea Kassner
Photograph courtesy of Laura Feldcamp

Stroke is the third leading cause of death in Canada and the primary cause of serious, long-term disability. There are over 50,000 strokes in Canada each year and over 300,000 Canadians are living with the effects of stroke.(1) My research focuses on novel imaging methods to quantify properties of the microvasculature in acute stroke patients and patients at high risk of stroke.

We conduct studies using dynamic contrast-enhanced magnetic resonance imaging (MRI) in combination with sophisticated image analysis techniques to assess the integrity of the cerebral microvasculature in acute ischaemic stroke (AIS). In healthy blood vessels, a special lining of endothelial cells make up a protective layer known as the blood-brain barrier (BBB), which allows oxygen and nutrients to pass into the brain tissue while blocking other compounds.(2) An ischaemic event can disrupt the integrity of the BBB, making it more permeable and susceptible to leakage. Dynamic contrast-enhanced MRI can quantify the concentration of a contrast agent over time as it is injected into the bloodstream, enters the cerebrovasculature, and accumulates around regions where the BBB is compromised.(3) Using advanced pharmaco-kinetic modeling tools, maps indicating vascular permeability can be generated to identify regions where vessel integrity may be particularly weak. Quantitative permeability MRI has potential significance in the treatment of AIS as the risk of intracerebral haemorrhage (the rupturing of cerebral arteries) is a major concern for AIS patients. This is particularly important as clinical therapy using thrombolytic agents is known to significantly increase the risk of haemorrhage. Our work so far has demonstrated the reliability of permeability measurements in predicting hemorrhage after initial AIS, comparing permeability imaging acquired using CT and MRI, and outlining the effect of reducing the total number of data samples used for permeability quantification. The aim is to select patients for clinical treatment based on precise physiological measurements to minimize the risk of subsequent complications.

Stroke is also one of the top ten causes of death in childhood and is as prevalent as brain cancer in children.(4) A recent investigation identified a number of chronic cerebrovascular diseases, such as moyamoya, transient cerebral arteriopathy and sickle cell disease (SCD) as major risk factors for childhood stroke.(5) Being based at the Hospital for Sick Children has given me a unique opportunity to study stroke risk and prevention in pediatric SCD. Currently, baseline blood flow velocity measured in the major cerebral arteries using transcranial Doppler ultrasound is the clinical standard for stratifying stroke risk in children with SCD. Although the application of Doppler ultrasound has been a significant milestone in the prevention of stroke in SCD, arterial flow velocity remains an indirect measure and does not assess the actual physiological factors that lead to stroke. My lab is researching MRI measurements of cerebrovascular reactivity (CVR) as a novel screening tool for children with SCD. Cerebrovascular reactivity measurements can assess the capacity for cerebral blood vessels to dilate, which is critical for normal regulation of blood flow in the brain. Our study uses a specialized computer-controlled gas delivery system that provides a vasoactive stimulus to the participant. Simultaneously, the resulting changes in cerebral blood flow are quantified using blood-oxygen level dependent (BOLD) MRI. BOLD imaging is a technique that is often associated with brain activation in functional MRI but can also be applied to CVR studies by detecting the blood flow response to a global stimulus in the brain. Importantly, BOLD imaging is completely non-invasive and, unlike other nuclear imaging modalities, does not expose subjects to ionizing radiation. For the first time, we have demonstrated that CVR can reliably measure developmental vascular changes in the brain in children with and without SCD. We observed that children with SCD have poor CVR and are, therefore, hemodynamically compromised compared to healthy controls. We expect that CVR abnormalities in children with SCD are strongly associated with stroke incidence. The inclusion of BOLD-CVR imaging to routine clinical assessment of SCD could eventually lead to improved selection of candidates for restorative interventions such as transfusion therapy or revascularization surgery.

Dr. Andrea Kassner
Assistant Professor & Co-Director of Research, Department of Medical Imaging
Senior Scientist, Physiology & Experimental Medicine, The Hospital for Sick Children

Reference List

(1) Heart and Stroke Foundation. Stroke Statistics. 2007.
Ref Type: Online Source
(2) Kassner A, Mandell DM, Mikulis DJ. Measuring permeability in acute ischemic stroke. Neuroimaging Clin N Am 2011 May;21(2):315-xi.
(3) Kassner A, Thornhill R. Measuring the integrity of the human blood-brain barrier using magnetic resonance imaging. Methods Mol Biol 2011;686:229-45.
(4) Heart and Stroke Foundation. Stroke in children (Paediatric stroke). 2013.
Ref Type: Online Source
(5) Lanni G, Catalucci A, Conti L, Di SA, Paonessa A, Gallucci M. Pediatric stroke: clinical findings and radiological approach. Stroke Res Treat 2011;2011:172168.