Fluorescence lifetime imaging device for 5-ALA-guided neurosurgery

项目总结 5-ALA诱导的PpIX荧光引导手术(FGS)能够实时显示残留癌组织 在脑肿瘤切除过程中。这解决了外科肿瘤学中的一个关键需求，即识别 残留肿瘤可提高总体存活率，而保留正常组织则有利于 患者的生活质量。目前，外科医生在视觉上欣赏弱光下的PPIX荧光强度 使用改装后的显微镜观察条件。这种方法是定性的，就像对PpIX荧光的感知 强度受许多因素的影响，包括：1)用于照明的光源类型；2) 显微镜的工作距离，3)血液等内源性吸收物质的存在，4)不均匀 照射手术野，这一点尤其重要，因为手术侧边有残留肿瘤 由于荧光激发不足，可能会漏掉空腔。此外，在低光下运行 各种情况会扰乱手术流程。 我们在加州大学戴维斯分校的研究小组开发了一种基于荧光寿命(FLIM)的FGS方法，即 对室内光线高度敏感、定量和不敏感，解决了现有5-ALA FGS的挑战 仪器仪表。在最近的一项初步研究中，该系统的性能得到了评估，该研究展示了5-丙氨酸-2，4-丙二醛-2，4-丙二醛-2，5-丙二醛-2，5-丙二醛-2，4-丙二醛-5-丙氨酸-2，4-丙二醛-2，5-丙二醛-2，5-丙二醛-2，5-丙二醛-2，5-丙二醛-2，5-丙二醛-5-氨基丁酸-1，5-丙二醛-2，5-丙二醛-1，5-丙二醛-1，5-丙二醛-1，5-丙二醛-1，5-丙二醛-1，4，5-丙二醛-1，5-丙二醛-1，4，4-二磷酸- 人高级别和低级别胶质瘤患者体内诱导的PPIX荧光检测(患者在 手术)。 在这些结果的基础上，加州大学戴维斯分校的团队成员建立了Hilight Surgical，并肩负着使命 通过开发和商业化简单易用的成像系统来支持外科医生，这些系统提供准确、 关于荧光团聚集的定量信息，其价格点适合被 外科肿瘤学社区。我们计划开发和验证一个低成本、高性能的薄膜FGS系统 在这一阶段中，第一阶段的建议是： SA1：使用低成本高速模数转换器实现胶片数据采集和处理 数字转换器(ADC)和一个现场可编程门阵列。这将使系统的成本降低到原来的1/4 它的足迹。 SA2：描述这种替代数据采集和处理的性能 实现与参考研究级仪器进行了比较。 在这项工作结束时，我们将确定通过这项工作所取得的业绩 另一种低成本的数据采集和处理适合进行商业应用的开发 Flim装置专为5-ALA荧光引导手术的要求量身定做。

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.