Abstract:Registration of 3D anatomic structures to their 2D dual fluoroscopic X-ray images is a widely used motion tracking technique. However, deep learning implementation is often impeded by a paucity of medical images and ground truths. In this study, we proposed a transfer learning strategy for 3D-to-2D registration using deep neural networks trained from an artificial dataset. Digitally reconstructed radiographs (DRRs) and radiographic skull landmarks were automatically created from craniocervical CT data of a female subject. They were used to train a residual network (ResNet) for landmark detection and a cycle generative adversarial network (GAN) to eliminate the style difference between DRRs and actual X-rays. Landmarks on the X-rays experiencing GAN style translation were detected by the ResNet, and were used in triangulation optimization for 3D-to-2D registration of the skull in actual dual-fluoroscope images (with a non-orthogonal setup, point X-ray sources, image distortions, and partially captured skull regions). The registration accuracy was evaluated in multiple scenarios of craniocervical motions. In walking, learning-based registration for the skull had angular/position errors of 3.9 +- 2.1 deg / 4.6 +- 2.2 mm. However, the accuracy was lower during functional neck activity, due to overly small skull regions imaged on the dual fluoroscopic images at end-range positions. The methodology to strategically augment artificial training data can tackle the complicated skull registration scenario, and has potentials to extend to widespread registration scenarios.