Clinical integration of biophotonics for real-time intraoperative assessment of tumor margins in head and neck cancer

This dissertation presents an investigation of the clinical application of two state-of-the-art, label-free optical imaging techniques - hyperspectral imaging (HSI) and Raman spectroscopy - for the intraoperative assessment of tumor margins in HNSCC. Given the critical and ongoing challenge of accurate margin delineation in oncologic surgery, this work contributes to new technological solutions that overcome the limitations of current gold-standard practices, particularly the FSA. In a series of three linked studies, the feasibility, accuracy and integration of these biophotonic technologies into surgical workflows were investigated in detail. In the first study, in-vivo HSI was introduced using a CE-certified endoscopic system that enabled rapid (<3 minutes), spatially resolved visualization of tumor margins with promising diagnostic performance. In the second study, this approach was extended to freshly resected ex-vivo specimens, where controlled imaging conditions and co-registration with histopathology enabled the development and validation of deep learning models that achieved an overall classification accuracy of 98%. The third study investigated the real time use of in-vivo Raman spectroscopy for the characterization of tissue at the molecular level and demonstrated its ability to distinguish malignant from non-malignant tissue within the clinical timelines of surgery. Combined, these studies provide proof of concept for a hybrid, AI-assisted diagnostic approach in head and neck surgery, where HSI enables rapid, wide-area detection and Raman spectroscopy enables precise molecular validation. This two-modality strategy mimics the clinical paradigm of gross and microscopic examination and provides an integrated, digital extension of surgical decision making. This work not only advances the state of the art, but also provides a translational framework for the integration of advanced biophotonic tools into routine clinical practice.