dMRI-guided pre-operative planning for supra-total resection of high-grade gliomas

dMRI引导的高级别胶质瘤超全切除术前规划

• 批准号: 10635099
• 负责人: Constantinos George Hadjipanayis
• 金额: $ 8.78万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-22 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10635099
• 关键词: Academia; Adoption; Adult; Affect; Anatomy; Brain; Brain Neoplasms; Cancer Patient; Clinical; Clinical Management; Complement; Complex; Computer software; Data; Diffusion Magnetic Resonance Imaging; Edema; Evaluation; Excision; Fiber; Glioma; Goals; Image; Infiltration; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Maps; Medical; Methodology; Methods; Microscopic; Modeling; Nebraska; Nervous System Physiology; Neurologic; Neurologic Deficit; Neuronavigation; Operative Surgical Procedures; Pathway interactions; Patient-Focused Outcomes; Patients; Pennsylvania; Performance; Pilot Projects; Positioning Attribute; Progression-Free Survivals; Protocols documentation; Readiness; Recurrence; Reproducibility; Research; Safety; Side; Site; Software Design; Source; Standardization; Surgeon; Survival Rate; System; Technical Expertise; Techniques; Technology; Testing; Tissue Model; Tissues; Translations; Universities; Visualization; clinical efficacy; cohort; comparative; contrast enhanced; design; experience; fluorescence-guided surgery; functional electrical stimulation; improved; industry partner; method development; patient safety; preservation; prospective; prototype; technology platform; tool; tractography; treatment planning; tumor; ultrasound; white matter

ABSTRACT High-grade gliomas (HGGs) are the most common primary brain malignancy in adults associated with very poor survival rates despite various treatments. Surgery is the current mainstay treatment for HGGs, and the main factor affecting survival rates (in over two decades) has been the increased extent of resection targeting the “visible” contrast-enhancing tumor (CET) seen on conventional contrast-enhanced MR imaging. However, since then research has shown that it is the “invisible” non-enhancing tumor (NET) which leads to progression or recurrence in HGGs by infiltrating the surrounding white matter (WM) tracts. This has led to the adoption of a supratotal resection (SpTR) approach, which includes resection of the `invisible' (microscopic) cancer beyond the visible contrast enhanced margins. SpTR has been shown to result in better patient outcomes with progression-free and overall survival. SpTR is undertaken using a combination of intra-operative techniques but having a pre-op assessment of the functional anatomy will enhance the chances of preserving function and maximizing tumor resection. Thus, the overarching goal of this Academia-Industry partnership (AIP) is to provide a treatment planning tool that will facilitate safe SpTR maximizing the benefit of surgical therapy while preserving neurologic function. The partnership builds on the technical expertise of UPenn for method development, the translational expertise of Synaptive to integrate into a clinically deployable product, and Mount Sinai's clinical expertise in evaluating it on patients. In Aim 1, UPenn will optimize and evaluate a tracking paradigm that provides enhanced visualization of WM fibers in NET. This will entail by combining tissue modeling, fiber tracking and tract delineation in clinically feasible multishell dMRI and optimize the paradigm for reproducibility and generalizability across patients and acquisitions. A comprehensive comparison of the approach to research and clinical paradigm will also be undertaken using retrospective data. The prototype for this tractography paradigm will be integrated into the Synaptive neuro-navigation product incorporating clinical and regulatory needs, with rigorous testing. The design will be optimized to maximize clinical utility assessed through a multi-surgeon evaluation across different Synaptive sites. This will culminate in the creation of an enhanced planning tool. Finally, in Aim 3, a prospective pilot study will be undertaken to evaluate this tool on clinical efficacy for safe SpTR, with patients being longitudinally assessed for neurological deficits. At the end of this study, the extensive evaluations will position the tool to a point of readiness for FDA submission. The AIP will lead to an enhanced pre-operative planning tool to plan safe SpTR, complementing intra-operative functional mapping, fulfilling a crucial unmet clinical need. The extended resection that this tool will facilitate, will potentially lead to extended survival times and hence improve patient outcomes. Thus, this tool is expected to significantly impact the clinical management of brain cancer, by affecting surgical treatment.

抽象的 高级神经胶质瘤（HGGS）是成年人中最常见的原发性脑恶性肿瘤 生存率差dospite各种治疗方法。手术是目前对HGGS的主要治疗方法， 影响存活率的主要因素（在二十年中）是切除量的范围增加的程度 在常规对比增强的MR成像中看到的“可见”对比增强肿瘤（CET）。然而， 从那时起，研究表明，它是“无形”的非增强肿瘤（NET），导致进展 或通过渗透周围的白质（WM）散布在HGG中的复发。这导致采用 跨切除术（SPTR）方法，其中包括“无形”（显微镜）癌症的切除 可见的对比度增强了边缘。 SPTR已被证明会带来更好的患者结局 无进展和整体生存。 SPTR是使用术中技术组合进行的 但是，对功能解剖结构进行预先评估将增强保留功能的机会和 最大化肿瘤切除。这是这个学术界合作伙伴关系（AIP）的总体目标是 提供一种治疗计划工具，可促进安全的SPTR最大化手术疗法的好处 保留神经功能。该合作伙伴关系建立在upenn的技术专业知识的基础上 开发，突触的翻译专业知识，以集成到临床上可部署的产品中，以及 西奈山（Mount Sinai）对患者进行评估的临床专业知识。在AIM 1中，Upenn将优化和评估 跟踪范式可增强网络中WM纤维的可视化。这将结合起来 在临床上可行的多壳DMRI中，组织建模，纤维跟踪和划分描述，并优化 患者和购置的可重现性和概括性的范例。全面比较 研究和临床范式的方法也将使用回顾性数据进行。 该片段范围的原型将集成到突触神经运动产品中 结合临床和调节需求，并进行严格的测试。设计将被优化以最大化 通过跨不同突触部位的多野外评估进行评估的临床公用事业。这将达到高潮 在创建增强的计划工具中。最后，在AIM 3中，将进行一项潜在的试点研究 评估该工具的安全性SPTR的临床效率，患者对神经系统进行了纵向评估 缺陷。在这项研究结束时，广泛的评估将把工具定位为FDA的准备点 提交。 AIP将导致增强的术前计划工具来计划安全的SPTR，完成 术中功能映射，满足至关重要的未满足临床需求。该工具的扩展切除 将有助于促进，有可能导致延长生存时间，从而改善患者的预后。那，这个 预计工具会通过影响手术治疗来显着影响脑癌的临床管理。