Fluorescence lifetime technique for detection of radiation necrosis vs gliom

描述（由申请人提供）：本资助申请的目的是开发一种临床工具，用于在神经外科切除术或神经外科手术期间实时评估辐照脑组织。 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）后复发。然而，识别癌症复发由于放射性坏死的发展而变得复杂。在介入性神经外科手术中，快速区分放射损伤与复发癌是非常重要的。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，我们提出了一种无标记，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），这有利于快速在体内评价脑组织的生化和功能特性。所提出的技术可以多光谱评估多种细胞代谢产物（NAD（P）H和其他荧光成分，如蛋白质和脂质）的荧光衰减，非常适合于评估与放射性坏死，恶性和正常组织相关的生化特征。在这个R21应用中，我们将测试MS-TRFS检测与辐射坏死相关的脑改变的能力。将讨论两个具体目标。第一个目标是：（i）提供一个 与组织辐射坏死相关的时间分辨荧光特征的系统评价和（ii）支持有助于独特的自发荧光特征的生化成分的鉴定，所述特征可以作为辐射坏死的诊断标志物。第二个目标是在人类患者中进行概念验证研究，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MS-TRFS在这些临床前和临床研究中被证明在可靠地区分放射性坏死与其他脑组织类型方面有用，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或脑组织立体定位活检期间进行脑肿瘤手术切除。这有可能改善放射性坏死的临床管理和总体患者结局。此外，所需的小光纤探头尺寸使MS-TRFS作为临床前研究工具的进一步发展，可以发挥作用，在RT的优化。我们设想的MS-TRFS探头引入啮齿动物模型到肿瘤区域的神经介入技术也可以用于监测RT剂量和局部组织反应。

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.