Project Summary: Percutaneous liver tumor ablation procedures are performed with ultrasound (US), computed tomography (CT) and CT-fluoroscopy guidance. Each image guidance modality has strengths and weakness. US provides superior tissue contrast and real-time guidance; however, suboptimal or absent acoustic windows, motion (respiratory, bulk), and poor applicator conspicuity compromise precise tumor targeting and a widening skill gap limit widespread adoption. The larger field-of-view (FOV) provided by CT is critical for evaluating proximity of non-target anatomy; however, poor tissue contrast, limited access along the X-Y-Z axis, motion, and non- real-time guidance limit accurate tumor targeting. Magnetic resonance imaging (MRI) provides superior soft tissue contrast but presents challenges with the comparatively long acquisition times for real-time guidance and limited access within the scanner bore. Image fusion technologies attempt to harness the strengths of each modality. Unfortunately, current image fusion technologies are unable to sufficiently account for liver deformation, bulk respiratory and patient motion which compromise targeting. Further, they do not address challenges associated with US. An Academic Industrial Partnership is proposed to develop and validate a solution comprised of two primary elements. The first is a combined platform with a novel MRI compatible hands-free US and fast 3D deformable image registration for optimized simultaneous US and virtual MR image guidance in the ablation setting. The second element will be development of advanced MRI methods for real- time treatment monitoring through MR Thermometry in combination with near-real-time assessment of ablation zone margins using advanced diffusion and perfusion MRI. This solution will improve primary efficacy and reduce local recurrence after ablation of liver tumors. This proposal will focus on microwave ablation however the solution is applicable for a wide variety of thermal therapies.