One part of the research focusses on mechanisms and imaging of plaque stability. Rupture of an atherosclerotic plaque is the main cause of the clinical symptoms of cardiovascular diseases such as acute myocardial infarction and ischemic stroke. For a ‘plaque at risk’, the risk of rupture is determined by morphological, molecular, biological and biomechanical parameters of the plaque. Focusing on the carotid artery, the ParisK consortium will construct technological and translational platforms in which several novel imaging modalities will be advanced, validated and added to existing non-invasive imaging modalities to measure one or more parameters of plaque at risk. The data will be integrated to develop a novel heuristic algorithm that gives the predicted risk of rupture of an individual plaque, which will be validated in subsequent clinical studies.
The novel fundamental aspects of the CTMM project ParisK (plaque at Risk) are:
1) Advanced Molecular Imaging: The three different targets of plaque vulnerability are: a) fibrin, which is related to blood clotting, b) macrophages that are related to inflammation and c) neovascularization, which can cause leakage of red blood cells into the plaque and destabilize it. Methods will be developed to target contrast agents at these markers so that they can be imaged by MRI, ultrasound and/or PET-CT. Detection methods for neovascularization will also be developed based on clinically-approved non-targeted contrast enhanced MRI and ultrasound.
2) Biomechanics: Ultimately, plaque rupture is a strictly mechanical phenomenon. If the forces exerted exceed the strength of the cap, it will break. Extensive measurement and modeling to assess both stress and strength will therefore be part of the project.
3) Clinical validation of optimized and new imaging modalities, multi-modal integration and development of a plaque-at-risk algorithm: Optimized and new imaging modalities will be integrated into a platform of state-of-the-art traditional imaging methods such as MRI, CT and ultrasound. Two clinical studies will be performed. In the first, the newly developed and optimized imaging technologies will be validated. In this study, patients will be included who have more than 70% stenosis of the carotid artery that requires surgery. This will allow measurements to be directly related to the actual composition of the plaque. In the second study, 300 patients will be included in a prospective follow-up study to evaluate the predictive power of traditional and novel imaging technologies.

A new research program focusses on the heart and brain connections. While both cardiovascular disease and progressive loss of cognitive functioning are prominent features of an aging population, surprisingly few studies have addressed the link between the function of the heart and extracranial arteries on the one hand, and the brain on the other hand. Yet recent data indicate that despite the capacity of the brain to adapt cerebral blood flow to its own demand, systemic hemodynamic changes that are a function of heart, aorta and cerebropetal arteries may reflect on the cognitive functioning. In the current research proposal we will test the hypothesis that the combined effects of cardiac and large vessel diseases are important and potentially reversible, but underestimated causes of vascular cognitive impairment offering an excellent opportunity for treatment. In a true multidisciplinary and translational approach funded by a 5 million euro CVON grant and a Rembrandt grant, we will test this hypothesis by evaluating the quality of the cerebral autoregulation in CV patients, analyzing available epidemiological data sets, perform new cross sectional and longitudinal studies in
elderly patient populations and analyze and complement the data of a large epidemiological cohort with either vascular cognitive impairment, cardiac dysfunction, or carotid artery disease and evaluate the systemic and cerebral hemodynamic status with MRI and thoroughly test cognitive dysfunction. Animal studies will be used to dissect the mechanisms involved and to reveal novel leads for interventions. Studies on human vessels will provide insights in the extent and composotion of intracranial atherosclerosis.
Effective start/end date01/08/2011 → …

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