Fluorescence Lifetime Imaging/Spectroscopy System For Robotic Cancer Surgery Guidance

项目总结 在R01 CA187427的这次竞争更新中，我们将继续推进无标记荧光寿命 成像(FLIM)以增强广泛使用的达芬奇手术平台的功能，重点是 经口腔机器人手术(TORS)。加州大学戴维斯分校率先在手术中使用Flim和我们的合作伙伴， 直觉外科，是机器人辅助手术的全球领先者。到目前为止，我们已经演示了a) 点扫描胶片设备与达芬奇外科系统的协同集成(首创)；b) 这种方法在不改变传统手术方法的情况下改善TRS手术决策的潜力 临床方案；以及c)FLIM衍生参数检测生化和代谢的用途 口腔和口咽癌与周围正常组织的实时鉴别特征 就地就诊患者..我们还开发了用于实时动态增强成像的创新方法 影响手术视野的参数。利用在以下方面取得的主要成就和知识 当前的R01，此续订申请的首要目标是1)演示Flim的诊断 在前瞻性研究中的价值，通过考虑被确定为关键的 当前的R01，并利用术前成像和临床信息，以及2)增强 外科医生控制台上的基于Flim的分类器，用于术中实时反馈。为了实现我们的全面目标 目的：1.扩充电影数据库，开发组织类型分类器 (回顾分析)考虑生物变量(例如，患者的年龄/性别、肿瘤起源/位置)和 实验情况(例如，上皮表面与深层边缘，原发肿瘤未知)和前 手术计划中使用的手术影像(CT、PET)特征。目标2.制定、验证和执行法规 增强电影数据可视化的活动，以支持前瞻性临床研究。目标3.将Flim验证为 一项前瞻性研究分析中的实时Tors指导方法。 综上所述，本研究将论证FLIM用于术中实时监测的临床可行性和实用性。 口腔和口咽癌手术切缘的评估。获取的胶片参数数据库将 支持后续的大型临床试验，以实现组织自动分类和诊断预测。而当 这项应用的重点是Tors手术，这是一种基于无标记薄膜的组织评估，其特征是 简单、快速、灵活的数据采集和显示，可广泛应用于达芬奇等其他程序 外科系统广泛应用于各种肿瘤手术，包括泌尿外科、结直肠外科、妇科和 胸癌。

PROJECT SUMMARY In this competitive renewal for R01 CA187427, we will continue to advance label-free Fluorescence Lifetime Imaging (FLIm) to enhance the functionality of the widely-used da Vinci Surgical platform with an emphasis on Trans-Oral-Robotic-Surgery (TORS). UC Davis has pioneered the intra-operative use of FLIm and our partner, Intuitive Surgical, is the global leader in robotic-assisted surgery. To date, we have demonstrated a) the synergetic integration of a point-scanning FLIm device with the da Vinci Surgical System (first-of-its-kind); b) the potential of this approach to improve surgical decision-making during TORS without modifying conventional clinical protocols; and c) the utility of FLIM-derived parameters detecting biochemical and metabolic characteristics to distinguish oral and oropharyngeal cancer in real-time from surrounding normal tissue in patients in-situ.. We also developed innovative methods for real-time dynamic augmentation of imaging parameters on the surgical field of view. Capitalizing on the major accomplishments and knowledge gained under the current R01, the overarching objective of this renewal application is to 1) demonstrate FLIm’s diagnostic value in prospective studies by accounting for biological/experimental variables identified as critical under the current R01 and leveraging pre-operative imaging and clinical information and 2) enhance the visualization of FLIm-based classifiers on the surgeon console for real-time intraoperative feedback. To accomplish our overall objective, we propose three specific aims: Aim 1. Expand the FLIm database and develop tissue-type classifiers (retrospective analysis) accounting for biological variables (e.g., patient age/sex, tumor origin/location) and experimental situations (e.g., epithelial surface vs deep margins, tumors of an unknown primary) and the pre- operative imaging (CT, PET) features used in surgical planning. Aim 2. Develop, validate and perform regulatory activities for enhanced FLIm data visualization in support of prospective clinical studies. Aim 3. Validate FLIm as a means of real-time intraoperative TORS guidance in a prospective study analysis. In summary, this study will demonstrate the clinical feasibility and utility of FLIm for intraoperative real-time assessment of oral and oropharyngeal cancer surgical margins. The acquired FLIm parameter database will enable subsequent large clinical trials for automated tissue classification and diagnostic prediction. While the focus of this application is on TORS surgeries, the label-free FLIm-based tissue assessment, characterized by simple, fast and flexible data acquisition and display, can be broadly applied to other procedures as the da Vinci Surgical System is used in a wide range of tumor surgeries including urologic, colorectal, gynecologic, and thoracic cancers.