Radiotherapeutic dose escalation to dominant intraprostatic lesions (DIL) in prostate cancer could potentially improve tumor control. The purpose of this study was to develop a method to accurately register multiparametric magnetic resonance imaging (MRI) with CBCT images for improved DIL delineation, treatment planning, and dose monitoring in prostate radiotherapy. We proposed a novel registration framework which considers biomechanical constraint when deforming the MR to CBCT. The registration framework consists of two segmentation convolutional neural networks (CNN) for MR and CBCT prostate segmentation, and a three-dimensional (3D) point cloud (PC) matching network. Image intensity-based rigid registration was first performed to initialize the alignment between MR and CBCT prostate. The aligned prostates were then meshed into tetrahedron elements to generate volumetric PC representation of the prostate shapes. The 3D PC matching network was developed to predict a PC motion vector field which can deform the MRI prostate PC to match the CBCT prostate PC. To regularize the network's motion prediction with biomechanical constraints, finite element (FE) modeling-generated motion fields were used to train the network. MRI and CBCT images of 50 patients with intraprostatic fiducial markers were used in this study. Registration results were evaluated using three metrics including dice similarity coefficient (DSC), mean surface distance (MSD), and target registration error (TRE). In addition to spatial registration accuracy, Jacobian determinant and strain tensors were calculated to assess the physical fidelity of the deformation field. The mean and standard deviation of our method were 0.93±0.01, 1.66±0.10mm, and 2.68±1.91mm for DSC, MSD, and TRE, respectively. The mean TRE of the proposed method was reduced by 29.1%, 14.3%, and 11.6% as compared to image intensity-based rigid registration, coherent point drifting (CPD) nonrigid surface registration, and modality-independent neighborhood descriptor (MIND) registration, respectively. We developed a new framework to accurately register the prostate on MRI to CBCT images for external beam radiotherapy. The proposed method could be used to aid DIL delineation on CBCT, treatment planning, dose escalation to DIL, and dose monitoring.
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