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)是成人最常见的原发脑恶性肿瘤，与 尽管接受了各种治疗，但存活率很低。手术是目前治疗HGG的主要方法，而 影响生存率的主要因素(20多年来)一直是切除靶向范围的增加。 常规增强磁共振成像上可见的“可见”对比增强肿瘤(CET)。然而， 从那时起，研究表明，是“看不见的”非强化肿瘤(Net)导致了进展。 或通过渗入周围的白质(WM)束而复发。这导致采用了 一种上腹部切除(SPTR)方法，包括切除“看不见的”(微小的)癌症。 可见的对比度提高了利润率。SPTR已被证明可以导致更好的患者预后 无进展和总体生存。SPTR术中采用多种技术相结合的方法 但是，术前对功能解剖进行评估将增加保留功能和 最大限度地切除肿瘤。因此，这一学术界-产业界伙伴关系(AIP)的首要目标是 提供治疗计划工具，以促进安全的SPTR，最大限度地发挥手术治疗的好处 保护神经功能。这一合作伙伴关系建立在宾夕法尼亚大学的技术专长基础上 开发、Synaptive的翻译专业知识以集成到临床可部署的产品中，以及 西奈山在患者身上评估它的临床专业知识。在目标1中，宾夕法尼亚大学将优化和评估 跟踪范例，提供网络中WM纤维的增强可视化。这将需要通过将 临床可行的多层磁共振成像中的组织建模、纤维跟踪和束描绘以及优化 患者和采集对象的可重复性和普适性的范例。全面比较 还将使用回溯性数据对研究方法和临床范例进行评估。这个 这种脑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，并进行严格的测试。设计将进行优化，以最大限度地提高 通过跨不同突触部位的多名外科医生评估来评估临床实用性。这将会达到顶峰 在创建一个改进的规划工具方面。最后，在目标3中，将进行一项预期的试点研究，以 评估该工具对安全SPTR的临床疗效，并对患者进行神经学纵向评估 赤字。在这项研究结束时，广泛的评估将使该工具达到FDA的就绪点 呈件。AIP将导致增强的术前规划工具，以规划安全的SPTR，补充 术中功能定位，满足关键的未得到满足的临床需求。该工具扩大了切除范围 将促进，将潜在地导致延长生存时间，从而改善患者的预后。因此，这一点 该工具预计将通过影响手术治疗而显著影响脑癌的临床治疗。