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（由申请人提供）：恶性脑肿瘤的异常脉管系统是其灌注、氧合和治疗反应的关键决定因素，因此，评估临床前脑肿瘤模型的微脉管系统的早期结构和功能变化可以。为指导新疗法的剂量/安排以及提供患者复发和复发的早期可测量迹象提供宝贵的信息，然而，这需要能够评估体内变化的体内成像技术。肿瘤整个生命周期的微血管（~10 µm）形态和灌注是一种光学成像技术，可以满足这些要求，并且不需要使用外源荧光染料或造影剂。因此，我们建议建立一个最先进的无线头戴式 LSCI 系统，用于评估微血管结构和灌注的体内变化，并结合荧光模块，用于对缺氧诱导的绿色荧光蛋白 (GFP) 表达进行成像一个我们期望这种头戴式图像能够量化异常脑肿瘤微血管的生理后果，例如肿瘤血流量减少/间歇性和缺氧升高。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/功能并增强药物输送，我们将测试我们的头戴式成像仪的能力作为一个测试案例，我们建议表征临床使用的皮质类固醇地塞米松对 9L-HRE-GFP 脑肿瘤的“正常化”作用，我们期望 LSCI 能够揭示微血管系统向“更”的方向转变。正常的结构伴随着灌注的改善，荧光成像揭示了地塞米松导致的“血管正常化”后缺氧的缓解（即诱导型 GFP 表达的减少）。最后，我们期望本提案中开发的多模式（即 LSCI 和荧光）成像和诱导细胞系（例如 9L-HRE-GFP）的创新组合适用于涉及病理性脉管系统的其他疾病。拟议的研究将促进对脑肿瘤生物学的基本了解，并为脑肿瘤的临床前测试建立一个新的平台。针对人类脑肿瘤的新疗法。