Non-invasive ultrasound imaging of coronary microcirculation – CorUS

Coronary microcirculation (i.e coronary flow in vessels smaller than 300µm) plays a key role in the control of cardiac perfusion. The importance of coronary microcirculation for relevant pathological conditions including angina in patients with normal or near-normal coronary angiograms is increasingly recognized. Indeed, a large number of patients with anginal symptoms and ischemia on stress testing have a normal coronary angiogram and current evidences suggest that about two third of these patients have coronary microvascular dysfunction (CMD), also known as microvascular angina (MVA). Patients with CMD have poor prognostic with significantly higher rates of cardiovascular events, including hospitalization for heart failure, sudden cardiac death, and myocardial infarction (MI). Another important and frequent alteration of the microcirculation is associated to sustained myocardial hypoperfusion during acute myocardial infarction despite coronary revascularization. This so called no-reflow phenomenon remains largely underdiagnosed, and is associated with adverse outcome. Finally, there are also major evidences for CMD during heart failure with preserved ejection france (HFpEF). Despite the urgent clinical need, there are simply no techniques available routinely in clinic, to directly visualize the coronary microvasculature and assess the local coronary microvascular system. Up to date, only global indirect measurements through functional testing (PET, CMR and contrast echocardiography) or invasive measurements can provide hemodynamic information such as Myocardial Blood Flow (MBF) and Coronary Flow Reserve (CFR) in response to vasodilator effects.

In CorUS, a novel ultrasound technology will be developed to image the anatomy and the function of coronary vessels at the microscopic scale using a non-invasive and non-ionizing technology. This approach relies on ultrafast ultrasound imaging of the heart at 5,000 images/s, a breakthrough technology pioneered about twenty years ago by researchers of the laboratory Physics for Medicine Paris and more recently on the new technology of Ultrafast Ultrasound Localization Microscopy (ULM) which was introduced to resolve blood vessels at a micrometer scale in deep organs by tracking ultrasound contrast agents (microbubbles) circulating in the blood flow.

Cutting-edge technology will be developed in CorUS for local and direct imaging of the coronary blood flows at the microscopic scale to provide new anatomical and functional markers of the coronary microcirculation. Preliminary proof of concept experiments in perfused porcine hearts and in perfused beating rat hearts have demonstrated the feasibility of 2D and 3D coronary microcirculation imaging. This technology will be translated to large hearts application and the approach will be validated in vivo on preclinical large animal models with alteration of the coronary perfusion. Finally, a clinical proof of concept study will be performed on patients with coronary microcirculation alteration.

The main objectives of CORUS are:
1. To develop a new ultrasound technology for coronary microcirculation imaging
2. To validate the technology on large animal preclinical models of coronary microcirculation alteration
3. To perform a proof of concept clinical study on patients with coronary microcirculation disease

CorUS will have major impacts in the understanding, the management and the treatment of coronary artery diseases and the non-ionizing, non-invasive imaging technology developed in this project could become a major tool for the clinical investigation of microvascular coronary circulation at the patient’s bedside.