Coronary Flow Reserve Imaging without Tracers – COFLORES

Synopsis
The present proposal aims at providing a reliable, fully non-invasive, quantitative and repeatable cardiac MRI method for assessing Myocardial Blood Flow in rest and stress conditions, i.e. Myocardial Blood Flow and Coronary Flow Reserve (CFR) in humans and small animals. It is designed to make significant contributions to the understanding, diagnosis and treatment strategies of diabetes-related cardiac microvascular disease as a pathology with growing social impact. Original measurement techniques will be developed based on recent results obtained by the investigators. A previous version had been submitted earlier to the ANR TecSan 2013 call within main axis 1 (“Medical Imaging”) and had received an entirely positive evaluation. Partner 3's contribution has been increased consequently, and the interest of cardiac ASL versus DCE techniques has been clarified further.

The project has the following major goals

G1 - to build a validated non-invasive MRI method product for CFR assessment usable in clinical routine
G2 - to build a validated non-invasive MRI method product for CFR assessment usable in animal research routine
G3 - to produce clinically relevant results that demonstrate the usefulness of the technique in comparison to other existing techniques
G4 – to produce results contributing to the understanding of the development of non-ischemic CMP: diabetes, nutrition and obesity in animal models

The project will operate on two translational, but independent axes: clinical research and preclinical research. Both axes are strongly method-oriented during the first 24 months and become purely application-oriented in the last 10 months. The translational aspects are essential during both method development and studies on human subjects and animals. CRMBM's past experience with translational projects has shown that knowledge acquired during development on each branch strongly influences and strengthens the other branch in both ways.

The project will be carried out by CRMBM, Marseille and two leading international MR manufacturers on the clinical side (Siemens Healthcare) and on the preclinical side (Bruker Biospin). Both industrial contributors have long-standing partnerships with CRMBM in MR research.
The methods developed in this proposal rely on Arterial Spin Labeling (ASL) Magnetic Resonance Imaging, which provides tissue blood flow measurements without tracers. This method removes any limitations on repeatability and, more importantly, ensures compatibility with longitudinal studies. Sensitivity, cardiac and respiratory motion issues and long acquisition duration have in the past precluded this method from being applicable to the human heart in clinical routine. The investigators have strong and documented experience with ASL techniques and have, more recently, contributed to improving sensitivity with an original steady-pulsed ASL technique named cine-ASL (Capron 2013, Troalen 2013). In small animals, this technique was shown to substantially reduce acquisition time without compromising image quality. In humans, preliminary results obtained by the investigators show similar promising results (Capron T et al ISMRM 2013, oral presentation). The industrial partners will ensure optimal working conditions regarding their respective programming environments. Application of the methods to diabetic patients and animal models will be carried out during the third year along with delivery of product-ready techniques. As an outcome of this project, we expect the work to have impact on the way how MBF is assessed in the clinic and in animal studies. We will provide a radiation- and tracer-free method for measuring CFR as a major parameter involved in diabetic and other non-ischemic cardiomyopathies and demonstrate the usefulness of the developed techniques in this context.