Assessing myocardial fibrosis with spin locked MRI

Summary Myocardial fibrosis serves to define various cardiac diseases, and is very useful as an early marker of cardiovascular disease and its progression. Some myocardial fibrosis is reversible and can be surveilled to determine response to treatment. Late gadolinium enhancement (LGE) MRI is a robust method for sizing scar (focal fibrosis) regions. Diffuse fibrosis and hemorrhagic infarctions can be more difficult to assess well. A relatively new MRI method, spin locking or T1rho imaging, is thought to provide valuable information regarding myocardial fibrosis. However, many problems including a variety of implementations with wide-ranging T1rho values, challenging artifacts, possibly different values by sex and age, and a lack of gold standards has impeded the potential value of cardiac T1rho. Here we seek to improve and better understand the factors that influence spin locking cardiac MRI. This project will also enable improved understanding of the utility of non-contrast MRI methods that include T1rho for assessing myocardial fibrosis. We propose to develop and test new combination MRI methods to predict myocardial fibrosis without gadolinium. The aims and methods of this project are to (1) study the value of different T1rho methods and more conventional MRI techniques in preclinical models. The models will have either diffuse fibrosis from rapid pacing, or focal fibrosis from coronary injection of ethanol. Half of the studies will also include focal fibrosis from radiofrequency ablation lesions placed on the LV endocardium. Histology of these models will inform their utility in translational studies. (2) To develop and compare new combined multi- parametric cardiac MRI methods for quantitative fibrosis measurements. This includes validating the methods in the preclinical model of aim 1. (3) We will characterize the repeatability of the T1rho and other MRI methods, in patients with cardiac disease. The new gadolinium-free methods will also be evaluated for their ability to predict extracellular volume (ECV) maps. The relevance to public health is that myocardial fibrosis causes disability and death and current treatments are inadequate. The development and use of more accurate and repeatable measurements of myocardial fibrosis will improve diagnosis and evaluation of therapies. As well, validated MRI methods that do not use gadolinium contrast will lead to accelerated evaluation of clinical therapies, in particular therapies in patients with severe kidney disease where administering gadolinium is contraindicated for research.