Head and neck squamous cell carcinoma (HNSCC) has one of the highest rates of recurrence cases among solid malignancies. Recurrence rates can be reduced by improving positive margins localization. Frozen section analysis (FSA) of resected specimens is the gold standard for intraoperative margin assessment. However, because of the complex 3D anatomy and the significant shrinkage of resected specimens, accurate margin relocation from specimen back onto the resection site based on FSA results remains challenging. We propose a novel deformable registration framework that uses both the pre-resection upper surface and the post-resection site of the specimen to incorporate thickness information into the registration process. The proposed method significantly improves target registration error (TRE), demonstrating enhanced adaptability to thicker specimens. In tongue specimens, the proposed framework improved TRE by up to 33% as compared to prior deformable registration. Notably, tongue specimens exhibit complex 3D anatomies and hold the highest clinical significance compared to other head and neck specimens from the buccal and skin. We analyzed distinct deformation behaviors in different specimens, highlighting the need for tailored deformation strategies. To further aid intraoperative visualization, we also integrated this framework with an augmented reality-based auto-alignment system. The combined system can accurately and automatically overlay the deformed 3D specimen mesh with positive margin annotation onto the resection site. With a pilot study of the AR guided framework involving two surgeons, the integrated system improved the surgeons' average target relocation error from 9.8 cm to 4.8 cm.

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