Coregistered Fluorescence-Enhanced Resection of Malignant Glioma

描述(由申请人提供)：这项建议的长期目标是通过为神经外科医生提供在切除恶性胶质瘤(MG)过程中做出最佳术中决策所需的先进图像指导技术来提高患者的存活率。它将达特茅斯公司在开发开放式颅脑手术图像指导方面的长期兴趣和专业知识与多伦多大学在实现最先进的组织荧光监测仪器和程序方面的深度结合在一起，创造了前所未有的整合和合成，将常规体积成像(术前获得)与用于脑瘤切除指导的新型表面/亚表面荧光(术中获得)结合在一起。这项研究旨在通过探索联合注册的术中荧光成像(F1)作为术前MR引导的手术切除(MRGR)在手术后期的补充，来确定神经外科手术切除MG的最佳程序范例。还计划将新的光学技术，即定量(QFI)和深度分辨(DFI)的荧光成像(DFI)整合到手术环境中，以提供先前在最近文献报道的神经外科FIGR研究中未获得或评估的新信息。我们的期望是，这些新的QFI和DFI信号与PMR的联合注册将增强神经外科医生识别切除边缘的能力，与以前相比，在更广泛的组织学MG分级中，具有更高的肿瘤控制/治愈可能性，同时手术后继发功能损害的发生率更低。支持这项建议工作的具体目标是：(1)开发与PMR共同注册的透视镜(TM)F1，并使用该系统来量化(I)F1信号与PMR图像特征之间的空间相关性程度，以及(Ii)作为临床系列MG切除的组织学分级的函数，活体记录的FL信号强度相对于活检标本中测量的荧光团浓度。(2)开发扩展F1的QFI和DFI算法，并在一个用于临床前FIGR评估的新型独立(FS)平台上实现这些概念。(3)在幻影和动物研究中验证QFI和DFI的添加，最终在临床前评估试验中确定和定义先进TM实现的最佳设计特征和性能预期。(4)实施先进的TM系统(基于AIM#3数据)与PMR共同登记，并完成一系列临床病例，就手术切除的完全性而言，FIGR+MRGR和单独的MRGR在手术中和术后的组织学MG分级评估方面的有效性，以证明使用定量FIGR+MRGR方法在扩大组织学范围的手术准确性方面的改善。

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.