David Spence MD, FRCPC, FAHA, FCAHS
Professor of Neurology and Clinical Pharmacology, Western University
Director, Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute
My research is based on uses of ultrasound in stroke prevention. We use transcranial Doppler for risk stratification in asymptomatic carotid stenosis and for detection of right-to-left shunts in patients with suspected paradoxical embolism, and measurement of carotid plaque burden for risk stratification, management of patients and genetic research. In CAIN I am chair of Project 2, which is validating preoperative imaging of vulnerable plaque by 3D ultrasound, MRI, CT angio, contrast studies of plaque vascularity and PET/CT imaging of plaque inflammation, with 3D histology of carotid endarterectomy specimens.
I have been greatly influenced by Dr. Henry Barnett, with whom I trained in Neurology. He was the first to show that aspirin reduced the risk of stroke, was PI of the North American Carotid Endarterectomy Study, and a giant in stroke prevention. My greatest personal achievement has been the prevention of approximately 7000 strokes among the 30,000 patients referred to me; my greatest academic achievement has been the pioneering of measurement of carotid plaque burden for risk stratification, management of patients and genetic research.
Professor, Departments of Pathology and Clinical Neurological Sciences
Assoc. Dean (Admissions), Schulich School of Medicine & Dentistry
Western University and London Health Sciences Centre
As a Neuropathologist, my interests are in nervous system diseases with specialist training in the examination of the nervous system at the cellular level. A common focus in my research has been quantitative image analysis and three dimensional tissue reconstruction. In the CAIN2 project, my goal is to optimize this process for carotid endarterectomies, producing high-resolution annotated maps of carotid atheromas. These 3D maps of pathology provide a gold-standard for correlative studies with in-vivo and ex-vivo ultrasound, PET/CT and MRI data thereby improving the ability to image and triage patients with carotid atheromatous disease.
As a clinician and researcher, beyond my family and patients, my greatest fortune has come in the form of mentors, colleagues and collaborators, some of whom have played all three roles: Dr. John Kaufmann, Dr. Charles Drake, Dr. Fred Gage, Dr. Clayton Wiley, Dr. Harry Vinters, Dr. Bryan Richardson, Dr. Bertha Garcia, Dr. David Spence and Dr. Terry Peters. I can say that my greatest achievement to date is in being a parent.
Richard Frayne, PhD
Canada Research Chair in Image Science
Hopewell Professor of Brain Imaging
Professor, Department of Radiology, Department of Clinical Neuroscience, University of Calgary
My research interests include the development and application of new magnetic resonance imaging techniques for the study, detection and treatment of vascular disease. Specifically, imaging for stroke prevention and in acute stroke; small vessel disease, angiography in the lower limbs, and MR-based endovasculartherapy. I am also interested in advanced image reconstruction and signal processing strategies, and in the clinical vascular applications of molecular imaging and 3D ultrasound.
Sandra Black, MA, MD, FRCPC
Neuroscience Program Research Director, Sunnybrook Research Institute
Brill Chair in Neurology, Deptartment of Medicine, University of Toronto
Professor, Deptartment of Medicine (Neurology), University of Toronto
As a clinician scientist, I study neurological degeneration and regenerative processes at the integrative level. Specifically, my clinical research has focussed on the cognitive sequelae of stroke and stroke recovery, and the differential diagnosis and monitoring of dementia utilizing concurrent clinical, neuropsychological and neuroimaging measures. I have led multidisciplinary teams in conducting large-group prospective studies with a longitudinal design and labour-intensive acquisition of complex, multidimensional databases. Correlative quantitative neuroimaging provides insight into the biological constraints which are operative in disease progression or recovery. Such information is becoming increasingly important as new treatments come on line for stroke and for dementia, especially given rapid therapeutic advances in neurology in the last decade. It is becoming increasingly evident that Alzheimer’s and Cerebrovascular Disease frequently co-occur in older individuals and have synergistic effects on the clinical expression of dementia. This has beomce a major focus of our research efforts.
An active investigator in clinical trials for dementia and stroke for over 20 years, I have recently been a lead investigator for trials in Vascular Dementia, Severe Alzheimer's Disease and a disease modifying trial for Alzheimer's Disease.
In addition to these clinical studies I also have used experimental approaches aimed primarily at understanding mechanisms which underlie deficits in praxis, visual-spatial function, language, and attention in stroke and in Alzheimer’s Disease (AD). Using both single-case and group-study designs, I collaborate with leading cognitive neuropsychologists to address theoretical issues in brain-behaviour relationships. In these researches, selective vulnerability of degenerative processes and focal injury from stroke provide naturalistic models of ablation and adaptation in the human brain.
Carotid ultrasound is a valuable tool for measuring and tracking carotid plaque area over time. Dr. Spence outlines how 3D ultrasound methods are used to calculate plaque area, which is an important predictor of stroke, myocardial infarction and death, and to follow plaque progression or regression, which are critical treatment targets. Using this novel approach, Dr. Spence et al. have found that a change in therapeutic strategies, targeting the arteries and not LDL levels, has led to less disease progression in their test population despite a rise in mean patient age.
Exploring the characteristics of vulnerable plaque is pivitol to the understanding of atherosclerosis disease progression. Traditionally, this has been done through histology, allowing for risk categories to be created. Dr. Moody et al., are using MR imaging (and PET imaging through CAIN2) to investigate tissue character, which, when related to histology, may be used to predict future events. It is anticipated that this knowledge could then be used for screening, for future long term trials, and to predict disease progression in the brain.
Using specialized equipment and advanced software, Dr. Fenster et al. have extended 2 dimensional ultrasound images to 3 dimensional acquisition. Through further software development, it has been possible for his team to reconstruct and measure existing carotid plaque in real time, allowing for accurate mapping of plaque regression or progression over time. Looking forward, Dr. Fenster describes current programs attempting to semi-automate plaque tracing on images.
The ability to anticipate future ischemic events in the brain is the goal of CAIN1. This presentation given by Josephine Pressacco for Alan Moody, covers the hypothesis, rationale, methods, goals and status of the CAIN1 project as of April 2011. Building on work already accomplished, it is anticipated that high resolution MRI will be proven useful in predicting end organ ischemic events through detailed characterization of atherosclerotic plaques.
Working within the goal of CAIN2, Dr. Spence outlines the importance and methods towards outlining atherosclerosis patients would would benefit from intervention. It has been determined that those with microemboli and with greater than 3 ulcers benefit and that characteristics of individual plaque predicts outcome. CAIN2 strives to validate imaging methods for detection of vulnerable plaque.
Atherosclerosis is not a disease that happens in isolation and can often lead to Small Vessel Disease and other serious end organ effects. Dr. Sandra Black discusses in detail many of the consequences of atherosclerosis on brain, including overt stroke, covert strokes and other small vessel pathologies. Through the CAIN program, Dr. Black is using various MR imaging sequences to fully understand these effects.