Optical analogs to MRI contrast agents for surgical guidance of brain tumor resection

MRI 造影剂的光学类似物用于脑肿瘤切除术的手术指导

• 批准号: 10331016
• 负责人: Scott C Davis
• 金额: $ 60.9万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10331016
• 关键词: Address; Aftercare; Anatomy; Animal Model; Animals; Behavior; Biodistribution; Brain; Brain Neoplasms; Characteristics; Clinical; Clinical Management; Contrast Media; Couples; Craniotomy; Custom; Data; Data Sources; Development; Devices; Diagnosis; Diagnostic; Dose; Drug Kinetics; Evaluation; Excision; Family suidae; Financial compensation; Fluorescence; Fluorescent Dyes; Gadolinium; Glioma; Head; Human; Human Biology; Image; Intracranial Neoplasms; Investigation; Kinetics; Label; Lead; Literature; Magnetic Resonance Imaging; Malignant Neoplasms; Microscope; Modality; Modeling; Modernization; Molecular; Molecular Abnormality; Monitor; Monitoring for Recurrence; Normal tissue morphology; Operative Surgical Procedures; Optics; PPIX; Patient Care Team; Patient-Focused Outcomes; Patients; Play; Preparation; Problem Solving; Procedures; Progression-Free Survivals; Protocols documentation; Recurrence; Reference Standards; Resolution; Role; Signal Transduction; Structure; Surgeon; Time; Tissues; Tumor Tissue; Tumor-Derived; Update; Visual; Visual Fields; Xenograft Model; alternative treatment; analog; base; brain tumor resection; clinical imaging; clinical translation; contrast enhanced; design; experience; fluorescence-guided surgery; follow-up; improved; improved outcome; instrument; lead candidate; neoplastic cell; novel; novel strategies; optical imaging; prognostic indicator; standard of care; targeted agent; tomography; tool; tumor; tumor heterogeneity; tumor xenograft; ultrasound; uptake; whole body imaging

ABSTRACT Surgical resection is a fixture in the treatment of intracranial tumors, and there is mounting data indicating that overall and progression-free survival improve for gross total resection compared to subtotal resection. The current standard of care for managing intracranial tumors relies heavily on MRI of gadolinium-based contrast agents (Gd-MRI), which plays a central role in diagnosis, surgical planning, intra-surgical guidance, and follow-up monitoring. During surgery, patients are spatially registered to the pre-operative MRI and MRI-derived tumor contours projected over the visual field within the surgical microscope to guide resection. Despite the widespread deployment of these sophisticated tools in surgery, subtotal resection rates remain stubbornly high. The primary culprits include difficulty in identifying tumor visually and the diminishing accuracy of the pre-op registration due to brain deformation as the surgery progresses. In this context, expansive efforts have sought to alleviate these shortcomings, including the use of intra-operative stereovision and/or ultrasound with brain deformation models to update the pre-op MRI and the use of fluorescent agents to label tumor in the visual field. Although promising, both of these approaches have known shortcomings. Specifically, the data sources used for updating pre-op MRI are only surrogate correlates with MRI, and most current fluorescence guided surgery (FGS) efforts focus on targeted agents designed to mark molecular features of tumor cells, which have shown high intra-patient/tumoral heterogeneity. This project aims to solve both of these shortcomings directly by leveraging the existing clinical understanding of Gd-MRI in managing intracranial tumors. Specifically, we will identify and evaluate fluorescent agents that mimic the kinetic behavior of conventional MRI-based contrast agents to guide intracranial tumor surgery. This approach will transfer the well-understood behavior of Gd-MRI directly into the visual field, enable rapid, intra-surgical administration of the agent, and provide an ideal data input for updating of pre-op MRI during surgery. Our approach is premised on compelling preliminary data in small animal glioma models showing highly correlative uptake between Gd-MRI and several untargeted optical agents. To advance this strategy we will, (1) rigorously validate these results and examine additional optical agent candidates using MRI and our custom hyperspectral whole-body imaging cryomacrotome, (2) establish concordance between candidate optical agents and Gd-MRI in a new porcine glioma model using our intra-operative MRI facility and FGS instruments, and (3) assess the capacity to use the optical agent data to update the pre-op MRI. We will also quantitatively compare uptake of the candidate agents, Gd-MRI and ALA-PPIX, the current standard for FGS of glioma. Completing the aims of this project will establish the optical analog strategy as a compelling approach for surgical guidance and lay the groundwork for clinical translation.

抽象的 手术切除是治疗颅内肿瘤的固定装置，并且有固定数据表明 与小计相比 切除。当前管理颅内肿瘤的护理标准在很大程度上取决于 基于Gadolinium的对比剂（GD-MRI）在诊断，外科计划中起着核心作用， 手术内指导和后续监测。手术期间，患者在空间上注册 术前MRI和MRI衍生的肿瘤轮廓投射在手术中的视野上 显微镜指导切除。尽管这些复杂的工具广泛部署 手术，小计切除率仍然固执。主要罪魁祸首包括困难 视觉上识别肿瘤和由于脑变形而导致的OP登记的准确性降低 随着手术的进行。在这种情况下，广泛的努力试图减轻这些缺点， 包括使用术中立体电视和/或超声检查与大脑变形模型的使用 更新预盖MRI和使用荧光剂在视野中标记肿瘤。虽然 有希望的是，这两种方法都有已知的缺点。具体而言，用于 更新前MRI仅替代与MRI相关，并且大多数电流荧光引导 手术（FGS）的努力集中在旨在标记肿瘤细胞分子特征的靶向剂上 已经显示出高的患者/肿瘤异质性。该项目旨在解决这两个项目 直接利用对GD-MRI的现有临床理解直接缺点 肿瘤。具体而言，我们将识别和评估模仿动力学行为的荧光剂 常规基于MRI的对比剂指导颅内肿瘤手术。这种方法将转移 GD-MRI直接理解的行为直接进入视野，实现快速，外科手术的行为 给药代理，并提供理想的数据输入，用于在手术过程中更新前OP MRI。 我们的方法以引人注目的小动物神经胶质瘤模型的引人注目的初步数据为前提。 GD-MRI和几种未靶向的光学剂之间的相关摄取。为了推进这一策略，我们 （（1）严格验证这些结果，并使用MRI和 我们的自定义高光谱全身成像冷冻剖面机，（2）建立一致性 使用我们的术中MRI设施的新猪神经胶质瘤模型中的候选光学剂和GD-MRI 和FGS仪器，以及（3）评估使用光学代理数据更新前OP的能力 MRI。我们还将定量比较候选代理GD-MRI和ALA-PPIX的吸收， 胶质瘤FG的当前标准。完成该项目的目标将建立光学类似物 策略是一种令人信服的手术指导方法，并为临床翻译奠定了基础。