Fluorescence lifetime imaging device for 5-ALA-guided neurosurgery

PROJECT SUMMARY 5-ALA-induced PpIX fluorescence-guided surgery (FGS) enables real-time visualization of residual cancer tissue during resection of brain tumors. This addresses a critical need in surgical oncology as the ability to identify residual tumor leads to improvements in overall survival, whereas the sparing of normal tissue benefits the patient’s quality of life. Currently, surgeons visually appreciate the PpIX fluorescence intensity under low-light conditions using modified microscopes. This approach is qualitative as the perception of PpIX fluorescence intensity is influenced by many factors including: 1) the type of light source used for illumination, 2) the microscope’s working distance, 3) the presence of endogenous absorbers such as blood, and 4) non-uniform illumination of the surgical field which is especially critical as residual tumor present on the sides of the surgical cavity may be missed due to insufficient fluorescence excitation. Additionally, operation under low-light conditions disrupts the surgical workflow.Our research group at UC Davis has developed a fluorescence lifetime (FLIm) based FGS approach that is highly sensitive, quantitative, and insensitive to room light, addressing the challenges of the existing 5-ALA FGS instrumentation. The performances of this system were evaluated in a recent pilot study demonstrating 5-ALA- induced PpIX fluorescence detection in human high- and low-grade glioma patients in vivo (patients during surgery).Building on these results, HiLight Surgical was established by team members from UC Davis with the mission to support surgeons by developing and commercializing easy-to-use imaging systems that provide accurate, quantitative information about fluorophore accumulation, at a price point suitable for broad adoption by the surgical oncology community. We plan to develop and validate a low-cost, high performance FLIm FGS system in this phase I proposal by:SA1: Implementing FLIm data acquisition and processing using a low-cost high-speed analog-to- digital converter (ADC) and an FPGA. This will enable a ~4-fold cost reduction of the system as well as reduce its footprint.SA2: Characterize the performance of this alternative data acquisition and processing implementation compared to the reference research-grade instrumentation.At the conclusion of this work, we will have determined whether the performance achieved with this alternative low-cost data acquisition and processing is suitable to proceed with the development of a commercial FLIm device well-tailored for the requirements of 5-ALA fluorescence-guided surgery.