Stimulated Raman scattering spectroscopic optical coherence tomography (SRS-SOCT) for label-free molecular imaging of brain tumor pathology

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The extent of resection of brain tumors is one of the most important factors associated with prolonged survival for patients with brain cancer. Unfortunately, achieving complete resection of the preoperatively-defined tumor region remains a significant clinical challenge. This is due, in part, to the lack of intraoperative tools available to help surgeons differentiate between healthy tissue that is crucial for neurological function and cancerous tissue. Further, there is no existing clinical technology, intraoperative or preoperative, that is able to identify infiltrative brain cancer cells. The goal of our R21 application is to advance a novel optical molecular imaging method— stimulated Raman scattering spectroscopic optical coherence tomography (SRS-SOCT)—and demonstrate that it can overcome current clinical limitations for identifying brain tumors and their margins. This novel approach leverages (1) the spatial and spectral multiplexing capabilities of SOCT to achieve fast, volumetric, molecular imaging with high spatial resolution; and (2) the rich molecular information provided by vibrational spectroscopy (via SRS) to clearly differentiate between cancerous and healthy tissues (i.e., provide contrast for disease). This novel SRS-SOCT technology overcomes significant limitations of previous methods (including OCT and SRS alone), and enables fast, highly-specific, label-free molecular imaging that is uniquely suited for identifying brain tumor margins. The aims for this proposal are as follows: Aim 1, task 1 focuses on building an SRS-SOCT system with a novel laser light source that provides high spatially- resolved spectral information with high signal-to-noise ratio. Aim 1, task 2 will advance existing signal processing (computational) methods to extract the complex, spatially-resolved spectral information. Aim 2 will use a well-established bulk and infiltrative brain tumor animal model to evaluate the capabilities SRS-SOCT to identify tumor tissue. Finally, for Aim 3, we will further validate SRS-SOCT for identifying brain tumors using human specimens from frozen sections and freshly excised brain tumors. Because SRS-SOCT detects biochemical signatures from lipids and proteins, the method can also be of value for detecting tumors in other lipid rich tissues, such as breast. Successful completion of this work will demonstrate the potential of SRS-SOCT for identifying bulk and infiltrating brain tumors, paving the way for a novel intraoperative tool that has the potential to increase the success rate of neurosurgery and prolong survival for patients with malignant brain tumors.