Purpose. This paper introduces a new methodology for semi-automatic registration of anatomical structure deformations. The contribution is to use an interactive inverse simulation of physics-based deformable model, computed in real-time. Methods. The method relies on non-linear Finite Element Method (FEM) within a constraint-based framework. Given a set of few registered points provided by the user, a real-time optimization adapts the boundary conditions and(/or) some parameters of the FEM in order to obtain the adequate geometrical deformations. To dramatically fasten the process, the method relies on a projection of the model in the space of the optimization variables. In this reduced space, a quadratic programming problem is formulated and solved very quickly. The method is validated with numerical examples for retrieving some unknown parameters such as the Young's modulus and some pressures on the boundaries of the model. Results. The approach is employed it in the context of radiotherapy of the neck where weight loss during the 7 weeks of the therapy modifies the volume of the anatomical structures and induces large deformations. Indeed sensitive structures such as the parotid glands may cross the target volume due to these deformations which leads to adverse effects for the patient. We thus apply the approach for the registration of the parotid glands during the radiotherapy of the head and neck cancer. 2 Eulalie Coevoet et al. Conclusions. The results show how the method could be used in a clinical routine and be employed in the planning in order to limit the radiations of these glands.