A Wireless Laser Speckle and Fluorescence Imager for In vivo Brain Tumor Imaging

用于体内脑肿瘤成像的无线激光散斑和荧光成像仪

基本信息

批准号：
8735101
负责人：
Arvind P Pathak
金额：
$ 17.09万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-16 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8735101
关键词：
Adrenal Cortex Hormones Angiogenesis Pathway Architecture Blood Vessels Blood flow Brain Neoplasms Cell Line Cells Contrast Media Development Dexamethasone Disease Dose Drug Delivery Systems Elements Fluorescence Fluorescent Dyes Gene Expression Glioma Goals Green Fluorescent Proteins Head Human Hypoxia Image Imaging Techniques Knowledge Lasers Life Cycle Stages Magnetic Resonance Imaging Malignant Glioma Malignant neoplasm of brain Measurable Mission Modeling Morphology Noise Optics Patients Perfusion Physiological Public Health Rattus Recurrence Relapse Research Resolution Schedule Source Structure System Testing Therapeutic Transgenic Organisms Treatment Efficacy Tumor Angiogenesis Tumor Biology Tumor-Derived Wireless Technology angiogenesis bevacizumab cellular engineering charge coupled device camera data exchange fluorescence imaging gliosarcoma improved in vivo in vivo imaging innovation insight instrumentation lens meetings miniaturize novel novel therapeutic intervention optical imaging pre-clinical protein expression public health relevance research clinical testing response restoration tumor tumor microenvironment tumor progression

项目摘要

DESCRIPTION (provided by applicant): The abnormal vasculature of malignant brain tumors is a critical determinant of their perfusion, oxygenation, and response to therapy. Therefore, the assessment of early structural and functional changes in the microvasculature of pre-clinical brain tumor models can provide invaluable information for directing the dosing/scheduling of new therapies and providing early measurable signs of relapse and recurrence in patients. However, this requires an in vivo imaging technique capable of assessing changes in microvascular (~10¿m) morphology and perfusion over the entire life-cycle of a tumor. Laser speckle contrast imaging (LSCI) is an optical imaging technique that meets these requirements and does not require the administration of exogenous fluorescent dyes or contrast agents. Therefore, we are proposing to build a state-of-the-art wireless, head-mounted LSCI system for assessing in vivo changes in microvascular architecture and perfusion combined with a fluorescence module for imaging hypoxia-induced green fluorescent protein (GFP) expression in a transgenic brain tumor model (i.e. 9L-HRE-GFP). We expect this head-mounted image to enable quantification of the physiological consequences of abnormal brain tumor microvasculature, such as decreased/intermittent tumor blood flow and elevated hypoxia. Since certain therapeutics (e.g. anti-VEGF agents, dexamethasone etc.) have been shown to 'normalize' the structure/function of tumor vessels and enhance drug delivery, we will test the ability of our head-mounted imager to detect these changes. As a test case, we propose to characterize the 'normalizing' effects of the clinically used corticosteroid, dexamethasone, on 9L-HRE-GFP brain tumors. We expect LSCI to reveal a shift in the microvasculature towards a more 'normal' architecture accompanied by improved perfusion, and fluorescence imaging to reveal alleviation of hypoxia (i.e. a reduction in inducible GFP expression) following 'vascular normalization' due to dexamethasone. Finally, we expect the innovative combination of multi-modal (i.e. LSCI and fluorescence) imaging and inducible cell lines (e.g. 9L-HRE-GFP) developed in this proposal to be applicable to other diseases involving the pathological vasculature. Collectively, the results of the proposed studies will promote a fundamental understanding of brain tumor biology and establish a novel platform for the pre-clinical testing of new therapies against human brain tumors.

描述（由适用提供）：恶性脑肿瘤的异常脉管系统是其灌注，氧合和对治疗反应的关键决定剂。因此，评估临床前脑肿瘤模型微脉管系统的早期结构和功能变化可以提供宝贵的信息，以指导新疗法的给药/调度，并提供患者的早期救济和复发迹象。但是，这需要一种能够评估肿瘤整个生命周期的微血管（〜10€）形态和灌注的变化的体内成像技术。激光斑点对比度成像（LSCI）是一种符合这些要求的光学成像技术，不需要给予外源性荧光染料或对比剂。因此，我们提议建立一个最先进的无线，头部安装的LSCI系统，用于评估微血管结构的体内变化和灌注与荧光模块相结合，用于成像缺氧诱导的绿色荧光蛋白（GFP）在转基因脑瘤模型中（即9L-HRRE-GFP）。我们期望这种头部安装的图像能够量化异常的脑肿瘤微举行的身体后果，例如改善/间歇性肿瘤血流和缺氧升高。由于某些疗法（例如抗VEGF药物，地塞米松等）已被证明可以“正常化”肿瘤血管的结构/功能和增强的药物递送，因此我们将测试头部安装成像师检测这些变化的能力。作为测试案例，我们建议表征临床使用的皮质类固醇（地塞米松）对9升HRE-GFP脑肿瘤的“正常化”作用。我们预计LSCI会揭示微脉管系统的转变朝着通过改善的灌注和荧光成像完成的更“正常”的结构，以揭示由于地塞米松而引起的“血管归一化”后缺氧（即降低了诱导的GFP表达）。最后，我们期望该提案中开发的多模式（即LSCI和荧光）成像和可诱导细胞系（例如9L HRE-GFP）的创新组合适用于其他涉及病理脉管系统的疾病。总的来说，拟议的研究结果将促进对脑肿瘤生物学的基本理解，并建立一个新的平台，用于临床前测试针对人脑肿瘤的新疗法。