5-ALA-induced PpIX fluorescence-guided surgery (FGS) enables real-time visualization of residual cancer tissueduring resection of brain tumors. This addresses a critical need in surgical oncology as the ability to identifyresidual tumor leads to improvements in overall survival, whereas the sparing of normal tissue benefits thepatient's quality of life. Currently, surgeons visually appreciate the PpIX fluorescence intensity under low-lightconditions using modified microscopes. This approach is qualitative as the perception of PpIX fluorescenceintensity is influenced by many factors including: 1) the type of light source used for illumination, 2) themicroscope's working distance, 3) the presence of endogenous absorbers such as blood, and 4) non-uniformillumination of the surgical field which is especially critical as residual tumor present on the sides of the surgicalcavity may be missed due to insufficient fluorescence excitation. Additionally, operation under low-lightconditions disrupts the surgical workflow. Our research group at UC Davis has developed a fluorescence lifetime (FLIm) based FGS approach that ishighly sensitive, quantitative, and insensitive to room light, addressing the challenges of the existing 5-ALA FGSinstrumentation. 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 duringsurgery). Building on these results, HiLight Surgical was established by team members from UC Davis with the missionto 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 thesurgical oncology community. We plan to develop and validate a low-cost, high performance FLIm FGS systemin 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 reduceits footprint. SA2: Characterize the performance of this alternative data acquisition and processingimplementation compared to the reference research-grade instrumentation. At the conclusion of this work, we will have determined whether the performance achieved with thisalternative low-cost data acquisition and processing is suitable to proceed with the development of a commercialFLIm device well-tailored for the requirements of 5-ALA fluorescence-guided surgery.
Public Health Relevance Statement: PROJECT NARRATIVE
5-ALA-induced PpIX fluorescence guided surgery (FGS) enables real-time visualization of residual tumor tissue
during resection of brain tumors, improving overall survival. Currently, surgeons visually appreciate the
fluorescence intensity using modified microscopes under low-light conditions. This approach is qualitative and
disrupts the surgical workflow. We have demonstrated using research instrumentation that fluorescence lifetime
imaging (FLIm) enables highly sensitive and quantitative detection of PpIX during surgery. In this grant
application, we will develop a FLIm data acquisition and processing approach using a low-cost and high-
performance ADC with FPGA data processing that will lead to a 4-fold reduction in instrumentation costs and
thus facilitate the commercialization and broad adoption of FLIm FGS technology.
Project Terms: <5-ALA><5-Amino-4-oxopentanoic Acid><5-Aminolevulinic Acid><5-amino-4-oxo-pentanoic acid> | |
