Fluorescence lifetime method for guided therapy of brain tumors

描述(申请人提供)：我们建议临床评估和优化研究的时间分辨荧光光谱(tr-LIFs)技术在神经外科脑肿瘤切除术中识别肿瘤与正常脑组织。目前神经外科医生对浸润性神经胶质肿瘤手术的一个关键需求是能够区分正常大脑和神经胶质肿瘤。该项目旨在证明进一步开发一种基于荧光的设备的可行性，该设备将增强神经外科医生在手术中区分肿瘤和正常脑组织的能力，而不需要活检。该设备将使用TR-LIFs技术来识别肿瘤边缘，并评估诊断程序的有效性。如果成功，这项工作将：(I)增强神经外科医生在术中区分肿瘤和正常脑组织的能力，(Ii)提高脑活检诊断的特异性，以及(Iii)增加脑肿瘤影像完全切除的机会，降低正常脑组织切除的风险。通过使用现有的TR-LIFS研究原型设备和方法在术中测量人脑肿瘤(胶质瘤、脑膜瘤、转移瘤)的时间分辨自体荧光，这个STTR第一阶段项目将解决3个具体目标，这些目标将在2年内结合临床研究和功能研究：(1)详细了解人脑肿瘤及周围正常组织时间分辨光谱的可测量性，并评估实验误差和光学损失的来源，包括脑运动和血液吸收。(2)通过分析组织荧光特征，并与组织病理学、免疫组织化学及常规的术前、术中诊断技术(MRI、B超)进行比较，找出最佳的TR-LIFS特征/参数，以提供最佳的肿瘤与周围正常组织的鉴别。(3)开发和测试基于具有代表性的光谱特征子集的近实时TR-LIF数据分析和脑组织分类的算法/软件。第一阶段的结果将是一个足够的知识基础，以允许制造TR-LIFS原型设备，优化软件设计，并在第二阶段继续开发。虽然这个项目最初是为脑瘤的划分量身定做的，但该设备也可能应用于其他类型的肿瘤诊断。

DESCRIPTION (provided by applicant): We propose clinical evaluation and optimization studies of time-resolved fluorescence spectroscopy (TR-LIFS) technique for the intraoperative identification of tumor vs. normal brain during neurosurgical resection of brain tumors. A critical need currently for neurosurgeons operating on infiltrative glial neoplasms is the ability to distinguish between normal brain and glial tumor. This project is to demonstrate the feasibility of further development of a fluorescencebased device that will enhance the ability of neurosurgeons to distinguish tumor from normal brain intraoperatively without the need for biopsy. The device will use TR-LIFS technique to identify tumor margins and assess the efficacy of diagnostic procedures. If successful, this work will: (i) enhance the ability of neurosurgeons to distinguish tumor from normal brain tissue intraoperatively, (ii) improved specificity of diagnostic in brain biopsy, and (iii) increase the opportunity of image complete resection of brain tumors and decrease risk of resection of normal brain tissue. By measuring intraoperatively the time-resolved autofluorescence of human brain tumors (glioma, meningioma, metastatic) using an existing TR-LIFS research prototype apparatus and methodology, this STTR Phase I project will address 3 specific aims that combine clinical research and functionality studies over a period of 2 years: (1) To obtain a detailed knowledge of the measurability of time-resolved spectra from human brain tumors and surrounding normal tissue and to evaluate sources of experimental errors and optical loss including brain movements and blood absorption. (2) To identify the optimal TR-LIFS features/parameters which provide the best discrimination between tumor and the normal surrounding tissue by analyzing the characteristics of tissue fluorescence and comparing the spectroscopic findings to the tissue histopathology, immunohistochemical, and conventional pre-and intra-operative diagnostic techniques (MRI, Ultrasound). (3) To develop and test algorithms/software for near real-time TR-LIFS data analysis and brain tissue classification based on a representative subset of spectroscopic features. The result of Phase I will be a basis of knowledge sufficient to permit a TR-LIFS prototype device fabrication, optimized software design, and continued development in Phase II. While this project is initially tailored to brain tumors demarcation, the device could potentially be also applied to diagnosis of other tumor types.