Biomicromechanics of Heart Muscle Tissue Function

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

Biomicromechanics of Heart Muscle Tissue Function Ellen M. Arruda, Ph. D., PI Karl Grosh, Ph. D., co-PI Abstract Sixty thousand patients under the age of 65 die each year from end-stage heart failure in the U.S. as a result of cardiomyopathy. Cardiac function is altered as a result of both systolic and diastolic impairment; usually the diastolic dysfunction precedes the systolic component. There is a critical need for very early diagnosis of this disease in order to provide an appropriate treatment. The long-term objective of our work in this area is the development of an echocardiograph-based biosensor of heart muscle tissue for early non-invasive detection of cardiomyopathy. This will consist of an echocardiograph, a strain imaging module and a constitutive law for heart muscle tissue. Currently pressure loads can be estimated via real-time blood flow information available from the doppler ultrasound measurements of the echocardiograph. A module for strain imaging is available on only a few specialized machines, but it is currently not used for diagnosis. The third element that is critically needed in the development of a biosensor, and addressed in this Proposal, is a predictive constitutive model of the heart muscle tissue. The aim of this Project is to develop a constitutive law for cardiac muscle tissue that describes its overall motion in terms of its response to electrical and mechanical stimuli in vivo. This will enable a correlation between changes in tissue properties with various stages of disease and echocardiograph-identified changes in cardiac function with cardiomyopathy, as well as the establishment of non-invasive criteria for the early diagnosis of cardiomyopathy prior to the stage of systolic dysfunction. Strain speckle imaging via echocardiographs will also be developed in this Project to non-invasively detect early stages of disease in patients with cardiomyopathy. These studies will lead to a better understanding of the mechanism of this process and better and earlier treatment of these patients. Canines involved in current studies at University of Michigan, in various stages of health and cardiac disease, will be euthanized and their ventricles excised for investigation of the changes in cardiac tissue response with cardiomyopathy. Mechanical tests and histology will be conducted on the ventricle and papillary muscle tissue to characterize them. Changes in material properties and physical characteristics with diseased myocardium will be documented by using dilated and hypertrophied canine populations and comparing them to the healthy populations. Our orthotropic constitutive model for soft tissue will be extended by including the role of additional deformation mechanisms in the response of myocardium, such as muscle activity and viscoelasticity. Moreover, the ability of the modeling approach to continue to capture the response of diseased myocardium will be assessed using the various canine populations. Mechanisms of cardiomyopathies will be described in terms of the changes in the physical parameters in the model. A commerical ultrasound strain imaging module donated for this project will be tested as a tool for in vivo elastography using canines. The accuracy of this technique will be examined by in vitro mechanical testing of excised cardiac tissue from the same animals. Mechanisms for cardiomyopathy will be examined by comparing the response of the myocardium at various stages before and after rejection and comparing these with echocardiograph-identified changes in cardiac function in the same patients.