Within many computational models, the mammalian heart tends to be represented as a mechanical device instead of a physiological organ. The Cardiac Mechanics Research Group (CMRG), hosted at UCSD, the University of California in San Diego, is developing a biophysically based continuum model to enhance the geometric and structural images with anatomic and morphologic characteristics. As a result, the researchers are offered a more realistic tool to approach and examine the tissue properties and chemical interactions, next to the merely electro-mechanical changes within the heart. The detailed model will enable scientists to relate experimental observations on the biological and biophysical behaviour of the heart cells to clinically relevant aspects of the organ as a whole under both normal and deviating circumstances, due to disease.
Together with Dr. Jeffrey Omens, Dr. Andrew McCulloch is the principal investigator of the CMR Group within the Department of Bio-engineering at UCSD. This Senior Fellow from the San Diego Supercomputer Center (SDSC) was invited at the Intel Seminar Series presentation at SDSC to highlight the current CMRG projects, dealing with the study of the cardiac functions. In 1997, Intel offered a three year award of $2.4 million to twelve UCSD groups under the Intel Technology for Education 2000 Programme. The CMRG researchers used their share of the grant to install four machines suited for image and experimental analysis, image processing as well as the ongoing implementation of the continuum model software.
The interactive continuum software tool serves to model biological systems, such as cells, tissues and organs as continua. The model allows the CMRG to integrate structure and function as well as theory and experiment by means of the finite element method (FEM). Today, the application runs on Silicon Graphics workstations but there is a version available for the Cray T3E parallel supercomputer. The prolate spheroidal coordinate system is able to accurately represent both the compact shape and muscle fibre architecture of the heart's muscle walls. Thus, the Continuity software is very adequate for solving problems in 3D image modelling, 3D non-linear finite deformation elasticity and non-linear reaction-diffusion models applied to the mechanics and electro-physiology of the mammalian heart.
Various parameters, derived from laboratory research, are introduced to the continuum model for comparative study. For instance, the CMRG members are working with both anatomic elements from rabbit hearts which have been histologically processed, and sections revealing the orientations of the muscle fibres. A second project relates to the differences in heart muscle structure between normal and brittle-boned mice suffering from osteogenesis imperfecta (OI) because of a deficiency in the protein collagen. Research graduate, Sara Vaplon, discovered that OI mice have fewer and smaller collagen fibres whereas the mechanical muscle stiffness is substantially lower in the mutant strain. Surprisingly enough, the finit element models showed that OI mice develop variations in the residual stresses and muscle fibre structure which constitute beneficial adaptations to the deficiency of collagen.
As far as the human heart is concerned, the CMRG investigators study the relationships between the cellular and tissue structure of the ventricular myocardium as well as the mechanical and electro-physiological function of both the intact and affected organ. In ongoing projects, the mechanisms of ventricular mechano-electric feedback, the alterations during ventricular hypertrophy, and the flow-function relations during myocardial ischemia are unveiled. In tight collaboration with the Cleveland Clinic Foundation and the University of Auckland in New Zealand, the researchers explore the potential of a revolutionary surgical method for patients with severe heart failure. Through the combination of computational modelling with magnetic resonance imaging, the partners aim at predicting which patients effectively can be rescued, using surgical ventricular reduction.
The continuum model offers access to a database of geometric and material property information and allows for interactive tackling of research problems which are run in batch mode by use of a command file facility. The software is written in C, C++ and FORTRAN. The scientific work of the CMRG people is largely funded by the National Institutes of Health, the National Science Foundation, the American Heart Association, the Whitaker Foundation, and several corporate sponsors. For a detailed description of the continuum model, we refer to the Web site of the Cardiac Mechanics Research Group.