Integration of 5-ALA Fluorescence Lifetime Imaging with Stereotactic Surgical Navigation for Quantitative Real-Time Spatial Localization of Tumor During Neurosurgical Procedures

5-ALA 荧光寿命成像与立体定向手术导航相结合，用于神经外科手术过程中肿瘤的定量实时空间定位

• 批准号: 10578584
• 负责人: Orin Bloch
• 金额: $ 59.03万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578584
• 关键词: Acids; Adjuvant; Adopted; Aminolevulinic Acid; Anatomy; Area; Augmented Reality; Biopsy; Brain; Brain Neoplasms; Brain region; Clinical; Clinical Research; Computer software; Correlation Studies; Darkness; Data; Data Display; Detection; Disease; Emerging Technologies; Excision; FDA approved; Fiber; Fluorescence; Glioblastoma; Goals; Image; Imaging Device; Imaging technology; Infiltration; Light; Lighting; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Manufacturer; Measurement; Measures; Metabolism; Methods; Microinvasive; Microscope; Monitor; Nature; Neuronavigation; Neurosurgical Procedures; Newly Diagnosed; Normal tissue morphology; Operative Surgical Procedures; Optics; Patient imaging; Patients; Pharmaceutical Preparations; Physiologic pulse; Positioning Attribute; Postoperative Period; Process; Prognosis; Prospective Studies; Real-Time Systems; Resectable; Resected; Residual Neoplasm; Sampling; Scanning; Signal Transduction; Surface; Surgeon; Surgical margins; Surgically-Created Resection Cavity; System; Techniques; Technology; Time; Tissues; Tumor Burden; Tumor Tissue; Visual; Visualization; Work; brain based; brain tumor resection; clinical application; clinically significant; fluorescence imaging; fluorescence lifetime imaging; fluorescence-guided surgery; imaging system; improved; neoplastic cell; neurosurgery; novel; optical imaging; prospective; protoporphyrin IX; radiological imaging; software development; spatial integration; tool; tumor; virtual

PROJECT SUMMARY/ABSTRACT Maximal surgical resection of the most common primary brain cancer, glioblastoma (GBM), has been shown to improve overall survival in a highly morbid disease. However, delineation of residual tumor at the margins of surgical resections can be challenging using conventional techniques, and therefore the use of fluorescence guided surgery (FGS) has emerged as an adjuvant tool for tumor detection. At present, only one agent, 5- aminoleveulinic acid (5-ALA), is approved for detection of GBM during surgery. Metabolism of 5-ALA into protoporphyrin IX (PpIX) is detected qualitatively by wide-field fluorescence imaging through the surgical microscope. This intensity-based detection is non-quantitative and background light-sensitive, requiring the surgeon to work in a dark field. We have developed a fiber-based pulse-excitation time-resolved method for Fluorescence Lifetime Imaging (FLIm) to detect quantitative PpIX fluorescence in real-time under full illumination conditions. Our goal in this study is to integrate the point-scanning FLIm technology with an existing intraoperative stereotactic neuronavigation system produced by BrainLab to spatially co-register FLIm data across the surgical field for applicable surgical guidance. We aim to develop new software and tissue classifiers based on primary patient data, and to apply the integrated technology in a prospective clinical study to demonstrate the benefits for surgical navigation. To achieve the overall goal of developing a new integrated technology which is immediately applicable for routine use in brain tumor resections, we will undertake the following aims: Aim 1) To develop new software for integration of the FLIm device with the BrainLab neuronavigation system for real-time acquisition of spatial positioning of FLIm data and display of the data overlaid on the patient’s imaging in the navigation space. Aim 2) To develop classifiers for surgically resectable tumor based on PpIX fluorescence lifetime thresholds determined through a prospective study correlating FLIm data to tissue biopsies. Aim 3) To validate the accuracy of integrated FLIm-based navigation in identifying residual tumor tissue to facilitate a greater extent of resection in a prospective clinical study.

项目摘要/摘要 最常见的原发性脑癌胶质母细胞瘤（GBM）的最大外科手术切除已显示为 改善高病态疾病中的整体生存。但是，在边缘描绘残留肿瘤 可以使用常规技术对手术切除术进行挑战，因此可以使用荧光 指导手术（FGS）已成为肿瘤检测的调整工具。目前，只有一个代理，5- 在手术期间，批准氨基乙酸酸（5-ALA）用于检测GBM。 5-ala代谢 原源性IX（PPIX）是通过手术成像定性地检测到的 显微镜。这种基于强度的检测是非定量的，背景敏感的，需要 外科医生在黑暗的领域工作。我们已经开发了一种基于纤维的脉冲激发时间分辨用于 荧光寿命成像（FLIM）以实时检测定量PPIX荧光 照明条件。我们在这项研究中的目标是将点扫描的Flim技术与 由Brainlab生成的现有术中的立体定向神经导航系统空间共同注册FLIM 整个手术领域的数据，用于适用的手术指导。我们的目标是开发新软件和组织 基于主要患者数据的分类器，并将集成技术应用于前瞻性临床研究 证明手术导航的好处。 为了实现开发新的集成技术的总体目标，该技术立即适用 在脑肿瘤切除术中的常规使用，我们将承担以下目的：目标1）开发新软件 将FLIM设备与Brainlab神经量化系统集成，用于实时获取空间 FLIM数据的定位以及在导航空间中患者成像覆盖的数据显示。目的 2）开发基于PPIX荧光寿命阈值的可切除肿瘤的分类器 通过前瞻性研究确定将FLIM数据与组织活检相关联。目标3）验证 基于FLIM的综合导航的准确性，以识别残留的肿瘤组织，以促进更大程度的范围 在一项前瞻性临床研究中切除。