Carotid Atherosclerosis Plaques tissue and vascular microstructure evaluation by UltraSound – CARPUS

Every year, there are 140 000 new cases of the acute vestibular syndrome (AVS), 28000 of which were caused by a carotid plaque rupture resulting in a stroke. The current medical recommendation only considered the stenosis degree of the carotid artery to define a surgical treatment to restore the arterial lumen. However, the plaque composition is a better predictor of a plaque rupture or erosion event than the degree of stenosis. It is of great importance to developing biomarkers of plaque composition to treat patients with an unstable plaque but a low degree of stenosis and to limit unnecessary routine surgery for patients presenting a stable carotid plaque with a high degree of stenosis (>50%). Rupture-prone plaques may present a large lipid core and thin fibrous cap infiltrated by macrophages or a subocclusive thrombus. Erosion-prone plaques are composed of smooth muscle cells with a subocclusive thrombus, an intraplaque hemorrhage, or a calcific nodule. Rupture-prone plaques components evaluation may be realized with MRI sequences. Calcific nodules may be observed with positron emission tomography. Ultrasound imaging allows also getting insight into some components of a plaque. However, an imaging technique, non-ionizing and available, to characterize the composition of a plaque and to determine its vulnerability is still needed. The objective of this project is to develop ultrasound biomarkers related to tissue microstructure and microvascularization to assess the carotid plaque composition. To this end, two promising ultrasound strategies will be proposed: quantitative ultrasound techniques to evaluate the tissue microstructure for the detection of plaque components involved in its vulnerability and ultrasound localization microscopy to evaluate the vascular microstructure and so the presence of neovascularization in the plaque. Broadband and high-frequency ultrasound excitation (until 22 MHz) will allow better identification of plaques different components, and especially at the cellular scale, and to get a better understanding of ultrasound scattering by these components. Tissue microstructure biomarkers will be evaluated in-vitro and on ex-vivo carotid plaque after surgery. The possibility to characterize carotid plaques with a 3D ultrasound acquisition and a lower excitation frequency (around 8 MHz), adapted for a clinical study, will be investigated before the conduction of two clinical studies. The first one will allow confronting ultrasound biomarkers from patient plaques with a high degree of stenosis and requiring surgery with histology. In the second one, ultrasound biomarkers will be evaluated on patient plaques with various degrees of stenosis during their routine ultrasound examination and they will be compared to the plaque composition estimated from MRI. At the end of this project, we aim to develop an ultrasound prototype set-up to measure tissue and vascular microstructure biomarkers of carotid plaque from patients. Biomarkers may help to evaluate the vulnerability of a plaque through estimation of their composition as well as the presence of neovascularization. Both of these biomarkers are of great interest to the clinicians to assess the plaque vulnerability, establish a diagnostic and treat the patients.