Automated extended volume imaging of tissue using confocal and optical microscopy.

Conventional histologic techniques cannot readily be used for 3D reconstruction of large tissue volumes. We have developed an imaging rig which supports both confocal and light microscopy, and utilizes a surface imaging approach to serially image embedded tissue blocks while maintaining alignment and registration of the image series.

Constructing a tissue-specific model of ventricular microstructure.

Simulations of cardiac electrical activity are generally computed in idealized or generic domains. We have developed a semi-automated technique for imaging an extended volume of cardiac ventricular tissue at a resolution of approximately 1 microm, and constructing from those images a geometric and structural model with 10 microm resolution suitable for solving the bidomain equations. This technique enables experimental modeling and computer simulation to be integrated by constructing a tissue-specific structural model in less than one week. We demonstrate the use of this procedure applied to a sample of rat ventricle.

Mathematical model of geometry and fibrous structure of the heart.

We developed a mathematical representation of ventricular geometry and muscle fiber organization using three-dimensional finite elements referred to a prolate spheroid coordinate system. Within elements, fields are approximated using basis functions with associated parameters defined at the element nodes. Four parameters per node are used to describe ventricular geometry. The radial coordinate is interpolated using cubic Hermite basis functions that preserve slope continuity, while the angular coordinates are interpolated linearly. Two further nodal parameters describe the orientation of myocardial fibers. The orientation of fibers within coordinate planes bounded by epicardial and endocardial surfaces is interpolated linearly, with transmural variation given by cubic Hermite basis functions. Left and right ventricular geometry and myocardial fiber orientations were characterized for a canine heart arrested in diastole and fixed at zero transmural pressure. The geometry was represented by a 24-element ensemble with 41 nodes. Nodal parameters fitted using least squares provided a realistic description of ventricular epicardial [root mean square (RMS) error less than 0.9 mm] and endocardial (RMS error less than 2.6 mm) surfaces. Measured fiber fields were also fitted (RMS error less than 17 degrees) with a 60-element, 99-node mesh obtained by subdividing the 24-element mesh. These methods provide a compact and accurate anatomic description of the ventricles suitable for use in finite element stress analysis, simulation of cardiac electrical activation, and other cardiac field modeling problems.