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The assessment of the Plaque At RISK

Knowledge on new fundamental aspects of plaque rupture will be integrated into a platform of acknowledged non-invasive imaging technologies, thus creating a tool to assess the risk for stroke and acute myocardial infarction

Researchers: Guillaume Renaud, Zeynettin Akkus, Verya Daeichin Hans Bosch,   Klazina Kooiman, Nico de Jong, Ton van der Steen

Vulnerable plaque
Acute cardiovascular and cerebrovascular events such as acute myocardial infarction and stroke are caused by rupture of a vulnerable atherosclerotic plaque. A vulnerable plaque (i.e. a plaque at risk) consists of a necrotic core covered by a thin fibrous cap, the presence of inflammatory cells and/or blood cells in the plaque. The inflammation will weaken the cap, which may cause rupture. Rupture of the fibrous cap brings the necrotic core in contact with the blood which causes the formation of a thrombus that may occlude the vessel and results in an infarction.   

Aims of ParisK
The project Plaque At RISK (ParisK) is a cooperation between top academic and industrial groups in the Netherlands with the aim to develop an algorithm for the assessment of the plaque at risk for rupture. This algorithm is based on new biological knowledge of plaque rupture that will be integrated into a platform of acknowledged non-invasive (molecular) imaging technologies, thus creating a tool to assess the risk for stroke and acute myocardial infarction.

All input into the algorithm is concentrating on measurements to and modelling of the carotid artery. This will give directly insight into the risk of stroke, but will also be a model for risk of acute myocardial infarction.

Center for Translational Molecular Medicine (CTMM)
ParisK is financed by the Center for Translational Molecular Medicine (CTMM). CTMM is a public-private partnership that comprises a multidisciplinary group of parties – universities, academic medical centers, medical technology enterprises and chemical and pharmaceutical companies. CTMM headquarters are located at the High Tech Campus in Eindhoven, The Netherlands.

Biomedical Engineering in ParisK
In ParisK academic and industrial partners work together in six so called work packages. The Biomedical Engineering group takes part in work package 2, which focuses on novel imaging modalities including techniques for noninvasive and nontargeted detection and quantification of plaque vasa vasorum by ultrasound (carotid ultrasound using contrast microbubbles) and dynamic contrast-enhanced MRI (3T and 7T MRI). The aim is to quantify the distribution of small vessels in the plaque, the flow in those vessels and the origin of the flow (arterial or venous). 

Task 1:  Ultrasound contrast agents and pulse sequences
We will perform research on novel pulse sequences aiming at high-sensitivity contrast detection within the plaque based on nonlinearity, such as subharmonics or superharmonics. Improved contrast to tissue ratio, superior sensitivity and saturation artifact suppression are the main deliverables.

In vitro validation will be followed by large animal experiments. Implementation of these methods on the clinical ultrasound machine will be performed by Philips in close cooperation with Erasmus MC. Adaptation or bubble radius selection of the nontargeted contrast agents in conjunction with these pulse sequences will also be investigated in-vitro, to further optimize visualization of microvessels.

Task 2: Ultrasound image analysis
Research on novel image processing methods for segmentation, quantification and classification of vasa vasorum. This involves methods for motion compensation by registration, in conjunction with Maximum Intensity Projection for vessel path visualization and particle tracking for vasa vasorum trajectories and low-velocity flow estimation. These tools will be developed and tested on 2D and 3D ultrasound recordings of in-vitro and animal models and/or the first dataset of 25 patients, on which histology data will be available for crossvalidation. Over the plaque area, wash-in and wash-out curves of contrast will quantify contrast arrival times, flow, partial vasculature volume etc. Contrast arrival time is linked to its arterial or venous origin. Adaptation towards the optimized nontargeted bubbles is foreseen as well. The methods developed in this task will also be aimed at and used in targeted microbubble work.