Fluorescence lifetime technique for detection of radiation necrosis vs gliom

用于检测放射性坏死与神经胶质细胞的荧光寿命技术

• 批准号: 8702828
• 负责人: Laura Marcu
• 金额: $ 19.69万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702828
• 关键词: Address; Adult; Aftercare; Algorithms; Animal Model; Applications Grants; Area; Biochemical; Biochemical Markers; Biopsy; Brain; Brain Neoplasms; Caliber; Characteristics; Classification; Clinical; Clinical Management; Clinical Research; Cranial Irradiation; Craniotomy; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Evaluation; Excision; Fiber Optics; Fluorescence; Fluorescence Spectroscopy; Future; Glioma; Histocompatibility Testing; Histocytochemistry; Histology; Histopathology; Human; Immunohistochemistry; Injury; Intervention; Investigational Therapies; Label; Laboratories; Lipids; Malignant - descriptor; Malignant Neoplasms; Metastatic/Recurrent; Modeling; Monitor; Nature; Necrosis; Needle biopsy procedure; Neurosurgeon; Neurosurgical Procedures; Nonionizing Radiation; Normal tissue morphology; Operative Surgical Procedures; Optics; Outcome; Patients; Play; Pre-Clinical Model; Procedures; Proteins; Radiation; Radiation Injuries; Radiation necrosis; Radiation therapy; Rattus; Recurrence; Recurrent Malignant Neoplasm; Recurrent tumor; Risk; Rodent; Rodent Model; Role; Sampling; Sampling Errors; Scanning; Specificity; Surveys; System; Techniques; Technology; Testing; Time; Tissues; Work; base; brain surgery; brain tissue; brain tumor resection; cancer recurrence; clinically relevant; design; dosimetry; hypodermic needle; improved; in vivo; mind control; miniaturize; non-invasive imaging; novel; pre-clinical; pre-clinical research; prototype; public health relevance; rapid diagnosis; response; technology development; tool; tumor; two-dimensional

DESCRIPTION (provided by applicant): The objective of this grant application is to develop a clinical tool for real-time assessment of irradiated brain tissue during neurosurgical resection or stereotaxic biopsy in patients with brain tumor recurrence. Primary and many metastatic brain tumors recur after radiation therapy (RT). However, identifying cancer recurrence is complicated by the development of radiation necrosis. It is important to rapidly distinguish radiation-injury from recurrent cancer during interventional neurosurgical procedures. Radiation necrosis and cancer are managed very differently. To address this problem, we propose development of a label-free, non-ionizing tissue assessment technique, i.e. Multispectral Scanning -Time Resolved Fluorescence Spectroscopy (MS-TRFS), which facilitates rapid in vivo evaluation of the biochemical and functional characteristics of brain tissue. The proposed technique can multispectrally evaluate the fluorescent decay of multiple cellular metabolites (NAD(P)H and other fluorescent constituents such as proteins and lipids) and is well suited to assess the biochemical features associated with radiation necrosis, malignant, and normal tissue. In this R21 application, we will test the ability of MS-TRFS to detect brain alterations associated with radiation necrosis. Two specific aims will be addressed. The first aim is designed to (i) provide a systematic evaluation of time-resolved fluorescence features associated with tissue radiation necrosis and (ii) support the identification of biochemical components contributing to unique autofluorescence signatures that can act as diagnostic markers of radiation necrosis. The second aim is focused on a proof-of-concept study in human patients designed to demonstrate whether a clinically compatible MS-TRFS device can be used for rapid diagnosis of radiation necrosis in the brain. If MS-TRFS proves useful in reliably distinguishing radiation necrosis from other brain tissue types in these pre-clinical and clinical studies, we anticipate further development of a specialized clinical MS-TRFS-based tool to aid in brain tumor surgical resection in the presence of radiation necrosis or during brain tissue stereotaxic biopsy. This has the potential to improve the clinical management of radiation necrosis and overall patient outcome. In addition, the small fiber optic probe size required enables further development of MS-TRFS as a pre-clinical research tool that can play a role in the optimization of RT. We envision that a MS-TRFS probe introduced in a rodent model into a tumor region by neurointerventional technology could also be used to monitor RT dosimetry and local tissue response.

描述（由申请人提供）：本拨款申请的目的是开发一种临床工具，用于在神经外科切除或手术期间实时评估受照射的脑组织。 脑肿瘤复发患者的立体定位活检。原发性和许多转移性脑肿瘤在放射治疗（RT）后会复发。然而，由于放射性坏死的发生，识别癌症复发变得复杂。在介入神经外科手术过程中，快速区分辐射损伤和复发性癌症非常重要。放射性坏死和癌症的治疗方法非常不同。为了解决这个问题，我们建议开发一种无标记、非电离组织评估技术，即多光谱扫描-时间分辨荧光光谱（MS-TRFS），它有助于快速体内评估脑组织的生化和功能特征。所提出的技术可以多光谱评估多种细胞代谢物（NAD(P)H 和其他荧光成分，如蛋白质和脂质）的荧光衰减，并且非常适合评估与放射性坏死、恶性和正常组织相关的生化特征。在此 R21 应用中，我们将测试 MS-TRFS 检测与放射性坏死相关的大脑变化的能力。将解决两个具体目标。第一个目标旨在 (i) 提供 对与组织辐射坏死相关的时间分辨荧光特征进行系统评估，并且（ii）支持识别有助于识别可作为辐射坏死诊断标记的独特自发荧光特征的生化成分。第二个目标是针对人类患者进行概念验证研究，旨在证明临床兼容的 MS-TRFS 设备是否可用于快速诊断大脑中的放射性坏死。如果在这些临床前和临床研究中，MS-TRFS 被证明能够可靠地区分放射性坏死与其他脑组织类型，我们预计将进一步开发一种基于 MS-TRFS 的专门临床工具，以帮助在存在放射性坏死的情况下进行脑肿瘤手术切除。放射性坏死或脑组织立体定位活检期间。这有可能改善放射性坏死的临床管理和患者的整体预后。此外，所需的小光纤探针尺寸使得MS-TRFS能够进一步发展为临床前研究工具，可以在RT的优化中发挥作用。我们设想，通过神经介入技术将 MS-TRFS 探针引入啮齿动物模型的肿瘤区域，也可用于监测 RT 剂量测定和局部组织反应。