Cardiovascular disease and stroke remain the number one killer in developed countries. Acute coronary syndromes, sudden cardiac death and stroke are caused by the rupture of a vulnerable atheroma plaque (VP). Post-mortem histological studies have shown that a VP (either coronary or carotid) is typically composed of a large extracellular necrotic core and a thin fibrous cap infiltrated by macrophages. Rupture of the cap induces the formation of a thrombus which may obstruct the coronary or cerebral arteries, cause an acute syndrome and the patient death. Ultrasound (US) imaging looks promising because of the ability of this method to image the coronary and carotid walls. This imaging technique is used to detect VPs but it did not succeed so far to prospectively predict plaque rupture. Thus, the determination of morphological clinical criteria based on imaging of the lesion still provides rather imprecise and insufficient predictors of risk. Other factors must be taken into consideration to extend our knowledge of the VP rupture process. In such a context, French and Canadian groups involved in this research program showed that the mechanical properties of a VP are also of major interest, since it is now established that mechanical stress affects several cellular processes, which are central to the plaque's vulnerability status. Therefore, the challenge for the new generation of in vivo clinical imaging methods is that prediction of the VP rupture requires not only an accurate description of plaque morphology but also a precise knowledge of mechanical properties of all plaque constituents. Indeed, such knowledge will likely allow a precise evaluation of the thin-cap fibro-atheroma peak stress amplitude, which is a well known reliable predictor of plaque rupture. Therefore, the clinical success of a surgical intervention depends on knowledge of whether a carotid or coronary lesion is at risk for rupture and can be responsible for the development of neurological or cardiovascular events, respectively. The medical history and paraclinical tests are sometimes insufficient to resolve this uncertainty. The current inability of scientists to predict plaque rupture based on morphological characteristics of vulnerable plaque cannot alone be elucidated by experts in fundamental ultrasound or biomechanics, and validated by clinicians, but collectively addressed by synergically combining our expertises. MELANII France/Canada grant application will allow us to favour a pluridisciplinary approach through the creation of a bi-continent scientific consortium. Such a strategy is essential since it's the synergy between Canadian and French expert groups which will give the promise of the most successful issue of the project in hand. In such a spirit of designing new tools for a better diagnosis of cardiovascular and stroke events, Canadian scientists involved in this grant application developed and patented robust elastography approaches (EVE and NIVE) to estimate, with ultrasound, the deformation within the vascular wall induced by the natural cardiac pulsation. Concomitantly, French team involved in this grant designed and patented an original imaging modulography tool (iMOD), which allows to go one step further by highlighting both, plaque morphology and mechanical properties (modulogram). iMOD was specifically designed to determine - using the elastogram - the modulogram of complex VPs. A combined expertise in vascular elastography and modulography cannot be found in either France or Canada. Our original findings (EVE-Canada, NIVE-Canada and iMOD-France) will be combined and improved, in order to propose a novel powerful US technique for a better in-vivo detection of VPs. Hence, it is the right moment and essential today to transfer our novel invasive and non-invasive clinical diagnostic US technology combining our elastography/modulography (EVE, NIVE and iMOD) codes for a better in vivo evaluation of the risk of vulnerable carotid and coronary plaque ruptures. This constitutes the main goal of this ANR France / NSERC Canada MELANII grant application.

Ventricular arrhythmias (VAs) account for the vast majority of the 250,000 cases of sudden death recorded in Europe each year. VAs occur mainly in patients with cardiomyopathy. Intra fibrotic electrical reentrant circuits are the dominant electrophysiological mechanism. Catheter ablation is the main option for invasive treatment, involving destruction of the slow conducting channels within the scar to block the electrical circuits. Challenges related to adequate catheter placement over the target area, sufficient energy diffusion into the tissue, and lack of intramyocardial dynamic mapping result in only 30-50% of patients experiencing freedom from recurrence after ablation. The aim of the CALAMAR (ChemicAL Ablation and Mapping of ARrhythmias) project is to evaluate the use of ultrasound to 1) Map the myocardium during ablation procedure using electromechanical wave imaging (EWI); 2) Validate a disruptive strategy of "chemical" ablation combining microbubbles and ultrasound to open the blood-myocardium barrier, and lipid nanoparticles loaded with cardiotoxic agents to induce a chemical dechannelization.

The MIGRASENS ANR’s objective is to develop a new generation of water pollutants microsensors network based on the association of CVD graphene and Molecular Imprinted Polymer (MIP). By coupling the properties of the graphene in terms of conduction, robustness, electrochemical sensitivity and the MIP selectivity, the consortium wants to design a lab-on-chip for the detection of a wide scope of micropollutants highlighted in the Water Frameworks Directive. The ambition of this project is to go to the CVD graphene production to its integration in a multidetection lab-on-chip prototype. The success of the project relies on the complementary competencies of the consortium, which includes two societies DSA technologies (Orléans) and Annealsys (Montpellier) and two academic laboratories ICMN (Orléans) and L2C (Montpellier), will allow to have got an overall point of view. The main scientific challenge will be to optimize the electro activity of the graphene electrode by the control of the growth parameters of CVD graphene and to use it as conductive platform of the sensor.

Since the work of Thomas Young in 1808, it is well established that strain energy can be guided along a tube as a symmetric wave: it is the pulse wave created by heart beatings and felt by palpation along arteries. However, strain energy can also propagate as an antisymmetric wave, the so-called flexion pulse wave. This latter wave, although barely hidden by the first one, has never been reported up to now in blood vessels. Our long-term vision is that this new flexion pulse wave can bring a technology breakthrough in angiography, shall it be in ultrasounds, in magnetic resonance imaging, in optics or in scanner radiology. The advantage conveyed by the new flexion pulse wave when compared to the standard pulse wave is its slowness. For this reason, the estimation speed is easier, more reliable and can conduct to a more accurate biomarker of blood vessel aging and cardiovascular risks. The ambitious short-term targeted application is thus the development of an ultrasound medical device for early detection, screening and monitoring of cardiovascular risks, a major issue in the world. Already demonstrated at capillary scale level in retina and at a macroscale level in the carotid within UCBL laboratory in Lyon, this novel approach now needs clinical validation in CHU-Rennes and technologic maturation with the help of industrial partners, E-Scopics and ANSYS. This innovation strategy follows the logic of the ANR-PRCE funding.