Functional lymph angiography with NIR imaging

描述(申请人提供)：与其姊妹血管系统不同，淋巴循环在很大程度上逃避了临床前和临床研究，这是因为可用于非侵入性成像的淋巴结构和功能的方法有限。缺乏体内淋巴成像严重限制了我们在临床前模型中了解淋巴生物学、评估日益流行的人类疾病的淋巴成分以及对遗传性淋巴疾病进行有效的基因分型的能力。此外，人们对淋巴功能在健康和疾病中的生理反应知之甚少。在这项应用中，我们寻求开发使用近红外(NIR)时间无关和依赖技术以及相关显像剂的功能性二维淋巴成像和三维淋巴血管成像。我们寻求评估淋巴结构和在健康和疾病中的生理反应，更重要的是，为淋巴研究开发一个重要的和缺失的成像工具。具体地说，我们的目标是：(1)使用二维平面近红外成像技术展示正常人和淋巴功能障碍患者对淋巴功能的人体成像及其生理反应；(2)开发使用新型成像试剂评估主要淋巴干淋巴结构和功能的三维光学断层成像或血管成像方法；以及(3)展示新的近红外淋巴成像试剂用于人体三维光学淋巴血管成像。如果成功，我们将能够在通过基因分型得到分子诊断的有症状和家族性无症状的米尔罗伊氏症和淋巴水肿病患者中展示功能和结构成像。淋巴功能成像的能力将使我们能够了解淋巴管在健康和疾病中的作用。公共卫生相关性：淋巴管和淋巴功能障碍与许多日益流行的疾病有关。然而，Milroy‘s和淋巴水肿病是罕见的先天性淋巴水肿形式，为了解淋巴功能障碍提供了一个窗口。在这项工作中，我们首次开发了一种方法，使用新型近红外造影剂用于光学成像的微剂量给药，对这些患者的动态淋巴功能和结构进行成像。

DESCRIPTION (provided by applicant): Unlike its sister hemovascular system, the lymphatic circulation largely escapes preclinical and clinical investigation owing to the limited methods available to non- invasively image lymphatic architecture and function. The lack of in vivo lymphatic imaging severely limits our ability to understand lymphatic biology in preclinical models, to evaluate lymphatic components of human disease of increasing prevalence, and to stratify hereditary lymphatic diseases for efficient genotyping. Moreover, there is sparse understanding of the physiological responses of lymphatic function in both health and disease. In this application, we seek to develop functional 2-D lymph imaging as well as 3-D lymph angiography using near-infrared (NIR) time independent and dependent techniques and associated imaging agents. We seek to evaluate lymphatic architecture and physiologic responses in health and disease and more importantly, to develop an important and missing imaging tool for lymphatic research. Specifically, our aims are to: (1) Demonstrate human imaging of lymphatic function and its physiological response in normal subjects and patients who suffer from lymph dysfunction using 2-D planar NIR imaging techniques; (2) Develop 3-D optical tomography or angiography methods for evaluating lymph architecture and function in major lymphatic trunks using novel imaging agents; and (3) Demonstrate the use of new NIR lymphatic imaging agents for 3-D optical lymph angiography in humans. If successful, we will be able to demonstrate functional and architectural imaging in symptomatic and familial asymptomatic Milroy's and lymphedema distichiasis patients who are molecularly diagnosed through genotyping. The ability to image lymphatic function will enable us to understand the role of the lymphatics in health and disease. PUBLIC HEALTH RELEVANCE: Malfunctioning lymphatics and lymphatic function are implicated in many diseases of increasing prevalence. Yet Milroy's and Lymphedema distichiasis are rare, congenital forms of lymphedema which provide a window to understand lymph dysfunction. In this work, we develop an approach to image for the first time, dynamic lymph function and architecture in these patients using novel near-infrared contrast agents employed in microdose administration for optical imaging.