Fluorescence lifetime imaging device for 5-ALA-guided neurosurgery

项目摘要 5-ALA诱导的PpIX荧光引导手术（FGS）能够实时可视化残留癌组织 在切除脑瘤的过程中这解决了外科肿瘤学的关键需求，即识别 残留的肿瘤导致总生存率的提高，而保留正常组织则有利于 患者的生活质量。目前，外科医生在低光下视觉上欣赏PpIX荧光强度 使用改良的显微镜。这种方法是定性的，因为PpIX荧光的感知 强度受许多因素影响，包括：1）用于照明的光源的类型，2） 显微镜的工作距离，3）内源性吸收剂，如血液的存在，和4）不均匀 手术区域的照明，这是特别关键的，因为手术区域两侧存在残余肿瘤。 由于荧光激发不足，可能会错过空腔。此外，在低光下操作 会扰乱手术流程 我们在加州大学戴维斯分校的研究小组已经开发出一种基于荧光寿命（FLIm）的FGS方法， 高灵敏度、定量且对室内光线不敏感，解决了现有5-ALA FGS的挑战 仪器仪表在最近的一项试验研究中评价了该系统的性能，该研究表明5-ALA- 在体内的人类高级别和低级别胶质瘤患者中诱导的PpIX荧光检测（患者在 外科手术）。 基于这些结果，HiLight Surgical由加州大学戴维斯分校的团队成员建立，其使命是 通过开发和商业化易于使用的成像系统来支持外科医生， 关于荧光团积累的定量信息，价格适合于广泛采用 外科肿瘤学社区。我们计划开发和验证一种低成本、高性能的FLIM FGS系统 在第一阶段建议中： SA 1：使用低成本高速模数转换器实现FLIm数据采集和处理 数字转换器（ADC）和FPGA。这将使系统的成本降低约4倍， 它的足迹。 SA 2：描述此替代数据采集和处理的性能 与参考研究级仪器相比， 在这项工作结束时，我们将确定是否与此实现的性能 另一种低成本的数据采集和处理方法适合于继续进行商业开发， FLIm器械针对5-ALA荧光引导手术的要求量身定制。

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.