Fluorescence lifetime method for guided therapy of brain tumors

描述（由申请人提供）：我们提出了时间分辨荧光光谱（TR-LIFS）技术的临床评价和优化研究，用于在脑肿瘤的神经外科切除术期间术中识别肿瘤与正常脑。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区分正常脑和神经胶质肿瘤的能力。该项目旨在证明进一步开发基于荧光的设备的可行性，该设备将增强神经外科医生在术中区分肿瘤和正常脑的能力，而无需活检。该器械将使用TR-LIFS技术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）提高神经外科医生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，（iii）增加脑肿瘤图像完全切除的机会，降低正常脑组织切除的风险。通过术中测量人脑肿瘤的时间分辨自体荧光，（神经胶质瘤、脑膜瘤、转移性），该STTR I期项目将在2年内实现3个具体目标，即结合联合收割机临床研究和功能研究：（1）为详细了解时间的可量度性─从人脑肿瘤和周围正常组织中分辨光谱，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)通过分析组织荧光的特征并将光谱结果与组织组织病理学、免疫组织化学和常规术前和术中诊断技术（MRI、超声）进行比较，确定最佳TR-LIFS特征/参数，以最好地区分肿瘤和正常周围组织。(3)开发和测试用于近实时TR-LIFS数据分析和基于光谱特征的代表性子集的脑组织分类的算法/软件。第一阶段的结果将是知识的基础，足以允许TR-LIFS原型设备制造，优化软件设计，并在第二阶段的继续发展。虽然该项目最初是针对脑肿瘤划分的，但该设备也有可能应用于其他肿瘤类型的诊断。

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.