ABSTRACT The purpose of this Phase I project is to build, integrate, and test a deformable registration pipeline for PRISM in order to make its markerless registration process more robust. PRISM is a camera-projector surgical navigation tool (SNT) developed by Illuminant Surgical, Inc. that harnesses advances in computer vision and sensors to provide surgeons with a seamless navigational experience. Importantly, PRISM addresses three key barriers to universal adoption of SNTs: high acquisition cost by leveraging low-cost, commodity hardware, long and invasive registration processes by building a markerless alignment algorithm that uses only surface topography, and unintuitive visualization by utilizing dynamic projection mapping to display critical guidance information directly onto the surface of the patient’s skin. Currently, PRISM has established accurate, consistent dynamic projection mapping capabilities through phantom and cadaveric testing. PRISM also has a markerless registration process in place that can align a patient’s preoperative radiological imaging with their intraoperative position to display patient anatomy directly on top of its subdermal location. However, this registration process currently takes into account only rigid transformations (i.e., translations and rotations). In order to be significantly more robust and applicable to any sort of skin-surface changes that may occur in the clinical environment between the time a patient completes a preoperative scan and undergoes a procedure, Illuminant is focusing on building a deformable registration pipeline that will be able to account for significantly more planes of disturbance in the skin surface and better predict how that impacts the subdermal anatomy. Aim 1 of this project will be dedicated to the development of deformable registration software that can be integrated into the current PRISM suite, and Aim 2 will focus on testing the deformable pipeline on cadaveric specimens. Aim 2 will also serve as a pilot study for a future cadaveric validation test that will serve as the basis for clearance from the FDA through the De Novo pathway. PRISM’s first use case is in spinal surgeries, which are often leveraged to treat spinal degenerative disease and low back pain––diseases that become increasingly prevalent in patients as they age. Given the growing popularity of these spinal procedures and the fact that they require a high degree of accuracy, tools like PRISM that provide intuitive visualization and localization of spinal structures in an easy-to-set up and affordable manner hold great promise. If funded by the NIH SBIR grant, PRISM would be the first device of its kind to achieve these capabilities and commercialize.