Development of a Wearable Fluorescence Imaging Device for IntraoperativeIdentification of Brain Tumors

ABSTRACT Approximately 700,000 people in the United States are diagnosed with a primary brain tumor. Of these, malignant gliomas (MGs) account for approximately 40% of all intracranial tumors, with an overall survival rate of only ~34%. Surgical resection remains the cornerstone of therapy and the extent of resection correlates with survival. Fluorescence imaging has emerged as an adjunctive technique, allowing for real-time cancer-specific detection. Surgeries guided by fluorescence imaging achieve gross-total-resection (GTR) rates of 75-100%, which are significantly higher than conventional surgeries with GTR rates of 30-55%. However, most clinical-grade imaging systems are hampered by high costs, limited portability, and lack of operation flexibility. Some neurosurgical fluorescence microscopes cost upwards of ~$500K and weigh ~800 pounds (PENTERO® 900 with fluorescence kits, Carl Zeiss). Many surgeons prefer, and continue to use wearable surgical eye loupes, which allow for convenient and fast operation, but are not capable of fluorescence visualization. Supported by the STTR Phase 1 Award (R41CA243600) and Kentucky State Matching Fund, Bioptics Technology (BOT) has developed a low- cost wearable FLoupe™ device (US Patent Application #62/530,613, 2017) attached to surgical eye loupes for intraoperative identification of fluorescent MGs. We have tested FLoupe™ prototypes to image fluorescent MGs during surgery in a small group of patients. Comparable results are observed against the PENTERO® 900 system. Based on neurosurgeons’ feedback in Phase 1, this Phase 2 project will further optimize the headlights (LEDs), video camera, emission filters, electrical control system, and mechanical design of the FLoupe™ device in terms of weight, size, imaging quality, and ease to wear/operate (Aim 1). The optimized FLoupe™ device will be calibrated and validated against the PENTERO® 900 system for equivalence to image fluorescent MGs in a large group of patients (Aim 2). We expect that fluorescence images taken at the surgical site and from biopsied samples by both devices will be equivalent and agree with the blinded histopathological analyses (the gold standard). Resulting data will be used for FDA clearance via the pre-market notification 510(k) submission with the PENTERO® 900 system as the primary predicate. Compared to the PENTERO® 900 system, the FLoupe™ device is significantly less expensive (<$10K unit sale price), more compact (wearable), and easier to operate (hand free with wireless control). This affordable and wearable device will significantly increase the ability of neurosurgeons to conduct fast and thorough operations, thus improving patient safety and outcomes. At the end of this Phase 2, a clinical-grade FLoupe™ device will be generated as a pre-manufactured product for intraoperative identification of MGs. Moreover, the FLoupe™ device with a modular design is easily modified with optimized excitation lights and emission filters to image a variety of visible dyes (e.g., fluorescein, 5-ALA, methylene blue). Thus, our product has the potential to be incorporated in other surgical settings beyond brain tumor resection based on the fluorescence characteristics of cancers, thereby expanding its market share.