Due to being derived from linear assumption, most elastic body based non-rigid image registration algorithms are facing challenges for soft tissues with complex nonlinear behavior and with large deformations. To take into account the geometric nonlinearity of soft tissues, we propose a registration algorithm on the basis of Newtonian differential equation. The material behavior of soft tissues is modeled as St. Venant-Kirchhoff elasticity, and the nonlinearity of the continuum represents the quadratic term of the deformation gradient under the Green- St.Venant strain. In our algorithm, the elastic force is formulated as the derivative of the deformation energy with respect to the nodal displacement vectors of the finite element; the external force is determined by the registration similarity gradient flow which drives the floating image deforming to the equilibrium condition. We compared our approach to three other models: 1) the conventional linear elastic finite element model (FEM); 2) the dynamic elastic FEM; 3) the robust block matching (RBM) method. The registration accuracy was measured using three similarities: MSD (Mean Square Difference), NC (Normalized Correlation) and NMI (Normalized Mutual Information), and was also measured using the mean and max distance between the ground seeds and corresponding ones after registration. We validated our method on 60 image pairs including 30 medical image pairs with artificial deformation and 30 clinical image pairs for both the chest chemotherapy treatment in different periods and brain MRI normalization. Our method achieved a distance error of 0.320±0.138 mm in x direction and 0.326±0.111 mm in y direction, MSD of 41.96±13.74, NC of 0.9958±0.0019, NMI of 1.2962±0.0114 for images with large artificial deformations; and average NC of 0.9622±0.008 and NMI of 1.2764±0.0089 for the real clinical cases. Student's t-test demonstrated that our model statistically outperformed the other methods in comparison (p-values <0.05)
