Toward a Novel Powerful Technique to Detect in vivo Human Vulnerable Atherosclerotic Plaques: a Synergic Approach Combining Elastography and Modulography Methods – MELANII

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.