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.

摘要 高级别胶质瘤（HGG）是成人中最常见的原发性脑恶性肿瘤， 尽管有各种治疗，但存活率很低。手术是目前HGG的主要治疗方法， 影响生存率的主要因素（在二十多年的时间里）是切除靶向范围的增加 在常规对比增强MR成像上看到的“可见”对比增强肿瘤（CET）。然而，在这方面， 从那时起，研究表明，它是“看不见的”非增强肿瘤（NET），导致进展 或通过浸润周围的白色物质（WM）束而在HGG中复发。这导致通过了 一种耳背上切除术（SpTR）方法，包括切除“不可见”（显微镜下）的癌症， 可见的对比度增强的边缘。SpTR已被证明可以获得更好的患者结局， 无进展生存期和总生存期。SpTR是使用术中技术的组合进行的 但术前对功能解剖结构进行评估将增加保留功能的机会， 最大限度地切除肿瘤因此，这一学术界-工业界伙伴关系（AIP）的总体目标是 提供一种治疗计划工具，可促进安全SpTR，最大限度地提高手术治疗的受益， 保护神经功能该伙伴关系建立在宾夕法尼亚大学的技术专长的方法 开发，将Synaptive的翻译专业知识整合到临床可部署的产品中，以及 西奈山的临床专业知识，在评估它的病人。在目标1中，宾夕法尼亚大学将优化和评估一个 跟踪范例，提供了增强的可视化WM纤维在NET中。这将需要结合 在临床可行的多壳dMRI中进行组织建模、纤维跟踪和束描绘，并优化 在患者和采集中的可重复性和普遍性的范例。综合比较 还将使用回顾性数据对研究方法和临床范例进行分析。的 这种纤维束成像范例的原型将被集成到Synaptive神经导航产品中 结合临床和监管需求，进行严格的测试。设计将进行优化， 通过多名外科医生对不同Synaptive部位的评价评估临床效用。这将导致 创建一个增强的规划工具。最后，在目标3中，将开展一项前瞻性试点研究， 评价该工具在安全SpTR方面的临床有效性，对患者进行神经功能纵向评估 赤字在本研究结束时，广泛的评估将使该工具处于准备就绪的状态，供FDA使用。 成绩. AIP将带来一个增强的术前规划工具，以规划安全的SpTR， 术中功能标测，满足关键的未满足的临床需求。这种工具的扩大切除 将促进，将可能导致延长生存时间，从而改善患者的预后。因此，这 该工具预计将通过影响手术治疗来显著影响脑癌的临床管理。