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The quantitative estimation of regional cardiac deformation from three-dimensional (3-D) image sequences has important clinical implications for the assessment of viability in the heart wall. We present here a generic methodology for estimating soft tissue deformation which integrates image-derived information with biomechanical models, and apply it to the problem of cardiac deformation estimation. The method is image modality independent. The images are segmented interactively and then initial correspondence is established using a shape-tracking approach. A dense motion field is then estimated using a transversely isotropic, linear-elastic model, which accounts for the muscle fiber directions in the left ventricle. The dense motion field is in turn used to calculate the deformation of the heart wall in terms of strain in cardiac specific directions. The strains obtained using this approach in open-chest dogs before and after coronary occlusion, exhibit a high correlation with strains produced in the same animals using implanted markers. Further, they show good agreement with previously published results in the literature. This proposed method provides quantitative regional 3-D estimates of heart deformation.