Coregistered Fluorescence-Enhanced Resection of Malignant Glioma

描述（由申请方提供）：该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（MG）切除过程中进行最佳术中决策所需的先进图像引导技术来提高患者生存率。它融合了达特茅斯在开发开放式颅骨手术图像引导方面的长期兴趣和专业知识，以及多伦多大学在实现最先进的仪器和程序以监测组织荧光方面的深度，以创造前所未有的传统体积成像的集成和合成程度在脑肿瘤切除术期间，使用新的表面/亚表面荧光（在手术中获得）进行引导。所提出的研究旨在通过探索共配准术中荧光成像（FI）作为手术后期术前MR引导切除术（MRGR）的增强，确定MG神经外科切除术的最佳手术模式。还计划将新的光学技术，即定量（qFI）和深度分辨（dFI）荧光成像整合到手术环境中，这将提供最近文献中报告的先前神经外科FIGR研究中未获得或评价的新信息。预期这些新的qFI和dFI信号与pMR的共配准将增强神经外科医生识别切除边缘的能力，肿瘤控制/治愈的概率更高，继发于手术的功能损害的发生率更低，组织学MG等级的范围比以前可能的范围更广。支持该提议努力的具体目标是：（1）开发与pMR共配准的透过（操作）显微镜（TM）Fl，并使用该系统来量化（i）Fl特征和pMR图像特征之间的空间相关程度和（ii）相对于在活检标本中测量的荧光团浓度在体内记录的Fl信号强度，作为MG切除的临床系列中的组织学等级的函数。(2)开发用于增强FI的qFI和dFI算法，并在用于临床前FIGR评估的新型独立式（FS）平台中实现这些概念。(3)在体模和动物研究中添加qFI和dFI，最终进行临床前评价试验，确定并定义高级TM实现的最佳设计特征和性能预期。(4)实施与pMR共同配准的高级TM系统（基于Aim #3数据）并完成一系列临床病例，这些病例讨论了FIGR+MRGR与单独MRGR在切除完整性方面的疗效，在术中和术后评估了MG组织学等级，以证明通过定量FIGR+MRGR方法在扩大的组织学范围内提高了手术准确性。

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.