Multi-stage image registration based on list-mode proton radiographies for small animal proton irradiation: A simulation study.

We present a multi-stage and multi-resolution deformable image registration framework for image-guidance at a small animal proton irradiation platform. The framework is based on list-mode proton radiographies acquired at different angles, which are used to deform a 3D treatment planning CT relying on normalized mutual information (NMI) or root mean square error (RMSE) in the projection domain. We utilized a mouse X-ray micro-CT expressed in relative stopping power (RSP), and obtained Monte Carlo simulations of proton images in list-mode for three different treatment sites (brain, head and neck, lung). Rigid transformations and controlled artificial deformation were applied to mimic position misalignments, weight loss and breathing changes. Results were evaluated based on the residual RMSE of RSP in the image domain including the comparison of extracted local features, i.e. between the reference micro-CT and the one transformed taking into account the calculated deformation. The residual RMSE of the RSP showed that the accuracy of the registration framework is promising for compensating rigid (>97% accuracy) and non-rigid (∼95% accuracy) transformations with respect to a conventional 3D-3D registration. Results showed that the registration accuracy is degraded when considering the realistic detector performance and NMI as a metric, whereas the RMSE in projection domain is rather insensitive. This work demonstrates the pre-clinical feasibility of the registration framework on different treatment sites and its use for small animal imaging with a realistic detector. Further computational optimization of the framework is required to enable the use of this tool for online estimation of the deformation.