Pulsed-light illumination optical system integrated into surgical microscope for 5-ALA-induced tumor fluorescence detection without surgical process interruption

Glioblastoma remains the deadliest type of brain tumor: half of patients do not live more than 16 months, even when treated with surgery, chemotherapy, and radiation. Tracking systems can help neurosurgeons precisely identify tumor on MRI images. Nevertheless, the tumor often regrows a few centimeters from where the original tumor was. This is because at the time of the first surgery, the actual tumor cells are already invading the healthy tissue around the tumor. These ‘invaders’ are difficult to cut out because even when looking through the surgical microscope, the tumor margins and normal brain tissue look very similar. The emerging utilization of fluorescing biomarkers (e.g., 5-ALA) sensitive to genetic downregulation present in cancer cells improves the detectability of marginal glioma, albeit requiring to switch to the surgical microscope excitation (blue light) mode and dim the operation room lights, imposing difficulties for neurosurgeons and staff. Here, we present a portable fluorescence-guided surgery optical imaging system integrated into the conventional surgical microscope to give neurosurgeons a better tool to predict which tissue is normal and which contains the start of tumor invasion without the need to switch to the excitation mode. The system operates under the microscope’s white light illumination using pulsed fluorophore excitation with gated acquisition and provides helpful tumor tissue fluorescing contrast. Tissue-mimicking phantom imaging confirmed protoporphyrin IX detection down to 0.1μg/mL concentration. Brain tissue imaging ex-vivo and pre-clinical intracranial tumor resection demonstrated the system’s capability to provide a typical operating environment with auxiliary or augmented visualization of PpIX possible.