Label-free fluorescence lifetime imaging for intraoperative real-time guidance of neurological procedures

项目总结/摘要 脑肿瘤手术的结果主要取决于神经外科医生区分 异常和正常组织的实时检测。我们的目标是通过使用无标签的 荧光寿命成像（FLIm）检测组织生化和代谢特征， 并通过将FLIm集成到神经外科工作流程中， 以实时、可视的形式用于引导肿瘤活检和切除。FLIm衍生的组织荧光 特征信息将与术前MRI（pMRI）共同配准并投影到常规MRI上 手术显微镜视野（FOV）。这将改善肿瘤边缘的描绘，从而增加 脑活检的诊断率和肿瘤切除的范围。 所提出的FLIm技术将具有以下特点：（1）安全、快速、同步 测量多个光谱发射带中的时间分辨荧光衰减， 在外科医生选择的大面积组织的一次扫描测量中的广泛信息;以及（2） 快速分析、显示和增强荧光参数，实现光学成像的实时可视化。 将诊断信息编码到手术FOV上的数据。使用FLIm作为标准的拟议临床研究- 单独的工具将建立分类器，以将FLIm参数与特定的组织病理学相关联，这是一个重要的 进一步证明FLIm的诊断价值。建议将FLIm作为 神经导航系统和手术显微镜将为联合分析提供数据，以验证受益 神经外科手术中的FLIm诊断。提出了三个目标：目标1）构建和整合一个 FLIm器械作为常规神经外科工具的诊断辅助工具。目的2）临床评价 FLIm参数与不同组织病理之间的关系，并开发用于不同组织的分类器 类型目的3）通过前瞻性分析，将FLIm用于实时术中引导。 总之，本研究将证明FLIm用于术中实时监测的临床可行性和实用性。 神经外科切缘的评估和神经病理诊断率的提高。的 获得的FLIm参数数据库将使后续的临床试验能够进行自动组织分类， 诊断预测新型FLIm仪器，具有简单、快速、灵活的数据采集特点 和显示器，以及它与现有神经外科成像的无缝集成，将提供一个更便宜的 是术中MRI的替代方法，也是当前标准治疗诊断程序的有价值补充。 这一领域的成功将保证FLIM在外科肿瘤学（其他癌症）以及 用于治疗功能性神经系统疾病（例如癫痫、神经退行性疾病）的指导性干预。

PROJECT SUMMARY/ABSTRACT The outcome of brain tumor surgery is critically dependent on the neurosurgeon's ability to distinguish between abnormal and normal tissue in real-time. Our goal is to enhance this discrimination by using label-free Fluorescence Lifetime Imaging (FLIm) to detect tissue biochemical and metabolic characteristics that distinguish among different tissue types and, by integrating FLIm into the neurosurgical workflow, to provide this information in a real-time, visual format useful for guiding tumor biopsy and resection. FLIm-derived tissue fluorescence feature information will be co-registered with the preoperative-MRI (pMRI) and projected onto the conventional surgical microscope field-of-view (FOV). This should improve delineation of tumor margins and thus increase both the diagnostic yield of brain biopsy and the extent of tumor resection. The proposed FLIm technique will incorporate the following features: (1) Safe, rapid, and simultaneous measurement of time-resolved fluorescence decays in multiple spectral emission bands that will acquire extensive information in one scanning measurement of a large area of tissue selected by the surgeon; and (2) Fast analysis, display, and augmentation of fluorescence parameters that enable real-time visualization of optical data encoding diagnostic information onto the surgical FOV. The proposed clinical studies using FLIm as a stand- alone tool will establish classifiers to correlate FLIm parameters with specific tissue pathologies, an important step in demonstrating FLIm's diagnostic value. The proposed integration of FLIm as an adjunct to the neuronavigation system and surgical microscope will provide data for combined analysis to validate the benefit of FLIm diagnostics in neurosurgical procedures. Three aims are proposed: Aim 1) Construct and integrate a FLIm device as a diagnostic adjunct with conventional neurosurgical tools. Aim 2) Clinically evaluate the relationship between FLIm parameters and distinct tissue pathologies and develop classifiers for different tissue types. Aim 3) Validate FLIm for real-time intraoperative guidance through a prospective analysis. In summary, this study will demonstrate the clinical feasibility and utility of FLIm for intraoperative real-time assessment of neurosurgical margins and the resulting improvement in neuropathologic diagnostic yield. The acquired FLIm parameter database will enable subsequent clinical trials for automated tissue classification and diagnostic prediction. The new FLIm instrumentation, characterized by simple, fast and flexible data acquisition and display, and its seamless integration with existing neurosurgical imaging, will provide a less expensive alternative to intraoperative MRI and a valuable complement to current standard-of-care diagnostic procedures. Success in this area will warrant a more generalized use of FLIm in surgical oncology (other cancers) as well as guided interventions for treatment of functional neurologic diseases (e.g. epilepsy, neurodegenerative diseases).