Coregistered Fluorescence-Enhanced Resection of Malignant Glioma

描述（由申请人提供）：本提案的长期目标是通过为神经外科医生提供在恶性胶质瘤（MGs）切除过程中最佳术中决策所必需的先进图像引导技术来提高患者的生存率。它融合了达特茅斯大学长期以来在开发开放式颅脑手术图像指导方面的兴趣和专业知识，以及多伦多大学在实现最先进的仪器和程序监测组织荧光方面的深度，创造了前所未有的程度，将传统的体积成像（术前获得）与新的表面/表面下荧光（术中获得）整合和合成，用于脑肿瘤切除术的指导。该研究旨在通过探索术中共登记荧光成像（Fl）作为手术后期术前MR引导切除（MRGR）的增强，确定神经外科切除mg的最佳程序范例。还计划将新的光学技术，即定量荧光成像（qFI）和深度分辨率荧光成像（dFI）整合到手术环境中，这将提供在最近文献中报道的先前神经外科FIGR研究中未获得或评估的新信息。期望这些新的qFI和dFI信号与pMR的共同登记将增强神经外科医生识别切除边缘的能力，在更大范围的组织学MG等级的手术后继发功能损伤的发生率较低的情况下，具有更高的肿瘤控制/治愈的可能性。支持该提议努力的具体目标是：(1)通过（操作）显微镜（TM）开发与pMR共注册的Fl，并使用该系统量化(i) Fl特征与pMR图像特征之间的空间相关性程度；（ii）在临床系列MG切除术中，相对于活检标本中测量的荧光团浓度，体内记录的Fl信号强度与组织学分级的关系。(2)开发增强Fl的qFI和dFI算法，并在用于临床前FIGR评估的新型独立（FS）平台中实现这些概念。(3)在模拟和动物研究中验证qFI和dFI的添加，最终进行临床前评估试验，以确定和定义高级TM实现的最佳设计特征和性能期望。(4)采用先进的TM系统（基于Aim #3数据）与pMR共同注册，并完成一系列临床病例，研究FIGR+MRGR与单独MRGR在术中和术后跨组织学MG分级的切除完整性方面的疗效，以证明使用定量FIGR+MRGR方法在扩大的组织学范围内手术准确性的提高。

DESCRIPTION (provided by applicant): The long term goal of this proposal is to improve patient survival by providing the neurosurgeon with the advanced image-guidance technology necessary for optimal intraoperative decision-making during removal of malignant gliomas (MGs). It merges Dartmouth's long-standing interest and expertise in developing image-guidance for open cranial surgeries with the University of Toronto's depth in realizing state-of-the-art instrumentation and procedures for monitoring tissue fluorescence to create an unprecedented degree of integration and synthesis of conventional volumetric imaging (obtained preoperatively) with novel surface/subsurface fluorescence (obtained intraoperatively) for guidance during brain tumor resection. The proposed research is structured to identify the optimal procedural paradigm for neurosurgical resection of MGs by exploring coregistered intraoperative fluorescence imaging (Fl) as an augmentation of preoperative MR guided resection (MRGR) in the late stages of surgery. Integration of new optical technology, namely, fluorescence imaging that is quantitative (qFI) and depth-resolved (dFI) into the operative setting is also planned which will deliver new information not previously acquired or evaluated in prior neurosurgical FIGR studies reported in the recent literature. The expectation is that co-registration of these new qFI and dFI signals with pMR will augment the neurosurgeon's ability to identify resection margins with higher probability of tumor control/cure at a lower incidence of functional impairment secondary to surgery for a broader range of histological MG grades than has been previously possible. The specific aims that underpin the proposal effort are to: (1) Develop through-(operating)-microscope (TM) Fl coregistered with pMR and use this system to quantify (i) the degree of spatial correlation between Fl signatures and pMR image features and (ii) Fl signal strength recorded in vivo relative to fluorophore concentration measured in biopsy specimens as a function of histological grade in a clinical series of MG resections. (2) Develop qFI and dFI algorithms for augmented Fl and implement these concepts in a novel free-standing (FS) platform for preclinical FIGR evaluation. (3) Validate the qFI and dFI additions in phantom and animal studies culminating in a preclinical evaluation trial that identifies and defines the optimal design characteristics and performance expectations for an advanced TM realization. (4) Implement an advanced TM system (based on Aim #3 data) coregistered with pMR and complete a clinical series of cases which address the efficacy of FIGR+MRGR versus MRGR alone in terms of completeness of resection evaluated intra- and post-operatively across histological MG grades in order to demonstrate improvements in surgical accuracy for an expanded range of histologies with the quantitative FIGR+MRGR approach.