In this SBIR, Xigen proposes to develop a set of novel 3D registration algorithms and a software package for image-guided radiotherapy (IGRT). This novel software synergistically correlates cone-beam computed tomography (CBCT) phase-binned (or amplitude-binned) volumetric 3D images with real-time optical 3D (O3D) surface images to provide in-vivo accurate volumetric 3D location of the treatment target and surrounding anatomy of the patient in the treatment position in (near) real-time. CBCT can provide volumetric 3D/4D images of patient[unreadable]s anatomy prior to an IGRT session. However, due to acquisition speed and radiation exposure, CBCT is not suitable for continuous use in real-time patient monitoring. In contrast, optical 3D surface imaging can be performed in-vivo and continuously without any ionizing radiation. It however is not able to provide internal anatomy information. The innovative approach proposed herein inherits advantages of both the CBCT and the optical 3D surface imaging, while alleviating drawbacks of both. It promises to provide viable in-vivo solution to IGRT for significantly reducing errors in all three stages of radiation therapy (RT): (1) treatment planning;(2) patient setup for treatment;and (3) adaptation to inter-fractional anatomic changes and intra-fractional movement. To the best of Xigen's knowledge, there is no existing technology that can achieve similar performance of real-time surface-volumetric 3D imaging for IGRT.