Label-free fluorescence lifetime imaging for intraoperative real-time guidance of neurological procedures

无标记荧光寿命成像，用于神经系统手术的术中实时指导

• 批准号: 10529315
• 负责人: Orin Bloch
• 金额: $ 54.47万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10529315
• 关键词: Affect; Area; Biochemical; Biometry; Biopsy; Brain; Brain Neoplasms; Cauterize; Characteristics; Classification; Clinical; Clinical Research; Clinical Trials; Complement; Complex; Comprehensive Cancer Center; Conventional Surgery; Craniotomy; Data; Data Display; Databases; Diagnostic; Diagnostic Imaging; Diagnostic Procedure; Discrimination; Engineering; Environment; Epilepsy; Equipment; Excision; Fluorescence; Glioma; Goals; Harvest; Hemostatic function; Histopathology; Human; Image; Image-Guided Surgery; Imaging Device; Imaging Techniques; Imaging technology; Intervention; Label; Letters; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Manufacturer; Measurement; Metabolic; Microscope; Necrosis; Neoplasm Metastasis; Neurodegenerative Disorders; Neurologic; Neuronavigation; Neurosurgeon; Neurosurgical Procedures; Normal tissue morphology; Operative Surgical Procedures; Optics; Outcome; Pathologic; Pathology; Patient-Focused Outcomes; Patients; Predictive Value; Procedures; Property; Protocols documentation; Qi; Radiation necrosis; Resources; Scanning; Signal Transduction; Specimen; Surgeon; Surgical Oncology; Surgically-Created Resection Cavity; System; Techniques; Technology; Testing; Time; Tissue Sample; Tissues; Tumor Tissue; Validation; Visual; Visualization; brain abnormalities; brain tissue; brain tumor resection; cohort; data acquisition; diagnostic value; feature detection; flexibility; fluorescence lifetime imaging; image processing; imaging system; improved; instrumentation; learning progression; multidisciplinary; nervous system disorder; neuro-oncology; neuropathology; neurosurgery; novel; optical imaging; pragmatic implementation; prospective; real-time images; standard of care; success; temporal measurement; tool; tumor

PROJECT SUMMARY/ABSTRACT The outcome of brain tumor surgery is critically dependent on the neurosurgeon's ability to distinguish between abnormal and normal tissue in real-time. Our goal is to enhance this discrimination by using label-free Fluorescence Lifetime Imaging (FLIm) to detect tissue biochemical and metabolic characteristics that distinguish among different tissue types and, by integrating FLIm into the neurosurgical workflow, to provide this information in a real-time, visual format useful for guiding tumor biopsy and resection. FLIm-derived tissue fluorescence feature information will be co-registered with the preoperative-MRI (pMRI) and projected onto the conventional surgical microscope field-of-view (FOV). This should improve delineation of tumor margins and thus increase both the diagnostic yield of brain biopsy and the extent of tumor resection. The proposed FLIm technique will incorporate the following features: (1) Safe, rapid, and simultaneous measurement of time-resolved fluorescence decays in multiple spectral emission bands that will acquire extensive information in one scanning measurement of a large area of tissue selected by the surgeon; and (2) Fast analysis, display, and augmentation of fluorescence parameters that enable real-time visualization of optical data encoding diagnostic information onto the surgical FOV. The proposed clinical studies using FLIm as a stand- alone tool will establish classifiers to correlate FLIm parameters with specific tissue pathologies, an important step in demonstrating FLIm's diagnostic value. The proposed integration of FLIm as an adjunct to the neuronavigation system and surgical microscope will provide data for combined analysis to validate the benefit of FLIm diagnostics in neurosurgical procedures. Three aims are proposed: Aim 1) Construct and integrate a FLIm device as a diagnostic adjunct with conventional neurosurgical tools. Aim 2) Clinically evaluate the relationship between FLIm parameters and distinct tissue pathologies and develop classifiers for different tissue types. Aim 3) Validate FLIm for real-time intraoperative guidance through a prospective analysis. In summary, this study will demonstrate the clinical feasibility and utility of FLIm for intraoperative real-time assessment of neurosurgical margins and the resulting improvement in neuropathologic diagnostic yield. The acquired FLIm parameter database will enable subsequent clinical trials for automated tissue classification and diagnostic prediction. The new FLIm instrumentation, characterized by simple, fast and flexible data acquisition and display, and its seamless integration with existing neurosurgical imaging, will provide a less expensive alternative to intraoperative MRI and a valuable complement to current standard-of-care diagnostic procedures. Success in this area will warrant a more generalized use of FLIm in surgical oncology (other cancers) as well as guided interventions for treatment of functional neurologic diseases (e.g. epilepsy, neurodegenerative diseases).

项目摘要/摘要 脑瘤手术的结果严重依赖于神经外科医生区分 实时检测异常组织和正常组织。我们的目标是通过使用无标签来加强这种歧视 荧光寿命成像(FLIM)检测组织生化和代谢特征，区分 在不同的组织类型之间，通过将FLIM整合到神经外科工作流程中，来提供这一信息 以实时、可视的格式，有助于指导肿瘤活检和切除。薄膜衍生组织荧光 特征信息将与术前MRI(PMRI)共同配准并投影到常规 手术显微镜视野(FOV)。这应该会改善肿瘤边缘的描绘，从而增加 脑活检的诊断率和肿瘤切除的范围。 建议的成膜技术将包括以下特点：(1)安全、快速和同步 测量将获得的多个光谱发射波段中的时间分辨荧光衰减 由外科医生选择的大面积组织的一次扫描测量中的大量信息；以及(2) 快速分析、显示和增强荧光参数，从而能够实时可视化光学 将诊断信息编码到手术视野上的数据。建议的临床研究使用FLIM作为支架- 单独的工具将建立分类器来将薄膜参数与特定的组织病理相关联，这是一个重要的 在展示Flim的诊断价值方面迈出了一步。拟议将FILM整合为 神经导航系统和手术显微镜将为联合分析提供数据，以验证其益处 神经外科手术中的胶片诊断学。提出了三个目标：目标1)构建和集成 作为常规神经外科工具的辅助诊断工具的Flim设备。目的2)临床评价 薄膜参数与不同组织病理的关系及不同组织分类器的研制 类型。目的3)通过前瞻性分析，验证FLIM对术中实时指导的有效性。 综上所述，本研究将论证FLIM用于术中实时监测的临床可行性和实用性。 评估神经外科边缘和由此带来的神经病理学诊断效率的提高。这个 获得的薄膜参数数据库将使后续的临床试验能够进行自动组织分类和 诊断预测。新型薄膜仪器，具有数据采集简单、快速、灵活的特点 和显示器，以及它与现有神经外科成像的无缝集成，将提供更便宜的 这是术中MRI的替代方案，也是对目前标准护理诊断程序的宝贵补充。 在这一领域的成功将保证在外科肿瘤学(其他癌症)以及其他癌症中更广泛地使用FLIM 指导治疗功能性神经疾病(如癫痫、神经退行性疾病)的干预措施。