Anatomical and functional imaging of the conventional outflow pathway

传统流出通道的解剖和功能成像

• 批准号: 10752459
• 负责人: Raymond Fang
• 金额: $ 4.29万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10752459
• 关键词: 3-Dimensional; Anatomy; Angiography; Anterior; Aqueous Humor; Autopsy; Behavior; Biological Markers; Biomedical Engineering; Biophotonics; Blindness; Blood Vessels; Blood flow; Clinical; Clinical Medicine; Data; Development; Diameter; Dimensions; Distal; Doctor of Philosophy; Effectiveness; Environment; Eye; Foundations; Frequencies; Functional Imaging; Glaucoma; Goals; Height; Heterogeneity; Human; Image; Imaging technology; Individual; Intervention; Investigation; Light; Machine Learning; Maps; Measurement; Measures; Mentors; Methods; Modeling; Motion; Mus; Operating Rooms; Optical Coherence Tomography; Pathway interactions; Pattern; Pharmaceutical Preparations; Phase; Physicians; Physiologic Intraocular Pressure; Physiological; Physiology; Pilocarpine; Predisposing Factor; Procedures; Property; Publishing; Research; Research Personnel; Resistance; Resolution; Rodent; Sampling; Scheme; Structure; Structure of sinus venosus of sclera; Structure-Activity Relationship; System; Testing; Three-Dimensional Imaging; Tissues; Trabecular meshwork structure; Tracer; Training; Translating; Treatment Effectiveness; Variant; Veins; Visible Radiation; Visualization; Width; Work; anatomic imaging; anterior chamber; aqueous; clinical care; contrast imaging; density; design; digital; effective therapy; eye chamber; functional status; glaucoma surgery; graph theory; imaging modality; improved; in vivo; innovative technologies; mathematical model; mechanical properties; meter; minimally invasive; non-invasive imaging; optimal treatments; pharmacologic; pressure; response; retinal imaging; technical report; tool; treatment strategy

Project Summary: Glaucoma is the leading cause of irreversible blindness worldwide. Currently, the only effective treatment for glaucoma is intraocular pressure (IOP) reduction. Physiologically, IOP is regulated by the aqueous outflow from the anterior chamber of the eye, with the vast majority leaving through the conventional outflow pathway. Despite the importance of the conventional outflow pathway, essential questions such as the relative contribution of the distal pathway to outflow resistance and the factors predisposing regions of the outflow pathway to be high and low flow remain unknown. Emerging imaging modalities such as optical coherence tomography, mainly used for retinal imaging, can provide anatomical and functional information that will elucidate the physiological behavior of the outflow pathway in vivo. Recent evidence using aqueous angiography shows that flow patterns in the outflow pathway can be used to increase the effectiveness of minimally invasive glaucoma surgery (MIGS). The PI is an MD/PhD trainee who proposes to utilize the ultrahigh (~1.3 microns in tissue) axial resolution of visible-light optical coherence tomography (vis-OCT) to noninvasively assess the physiology of the conventional outflow pathway in vivo. Using the information acquired for OCT, the goal is to develop noninvasive methods to assess regional flow patterns and improve MIGS. Vis-OCT is capable of generating three-dimensional volumetric information consisting of both anatomical and functional data. Additionally, the shorter wavelengths of light used by vis-OCT increase its axial resolution and provides increased sensitivity to slower blood flow and motion. Since increased resistance in any portion of the outflow pathway influences outflow, the high resolution of vis-OCT will be used to generate quantitative anatomical and functional measurements for all parts of the outflow pathway (trabecular meshwork, Schlemm’s canal, and distal vasculature). Thus, it is hypothesized that anatomical and functional information generated from imaging the outflow pathway in rodents can serve as biomarkers for understanding the flow patterns within the outflow pattern. To investigate this hypothesis, the PI proposes two aims: Aim 1 utilizes vis-OCT for anatomical imaging, measuring Schlemm canal volume and distal vasculature structure to make predictions to discover structural- function correlates related to regional outflow. Aim 2 focuses on the development of functional metrics, including the response of the pathway to pharmacological interventions and motion of the trabecular meshwork in response to intraocular pressure changes, to predict regional outflow. The training environment is well suited for this investigation, with the mentors' labs being experts in designing OCT systems and the co-mentors lab being experts in imaging aqueous outflow. This research leverages a diverse group of mentors with expertise in biophotonics, physiology, biomedical engineering, and clinical medicine. In addition to training the PI to become an independent researcher, the training plan shall also prepare the PI to become one of the physicians most knowledgeable in imaging and translating innovative technologies into clinical settings.

项目摘要：青光眼是全球不可逆失明的主要原因。目前，唯一的 青光眼的有效治疗是眼内压（IOP）减少。从生理上讲，IOP受到 眼前房间的水出口，绝大多数人穿过传统 出口路径。尽管传统出口途径很重要，但诸如 远端途径对输出电阻的相对贡献和输出流的易感区域的因素 高流量和低流量的途径仍然未知。新兴成像方式，例如光学连贯性 断层扫描主要用于视网膜成像，可以提供解剖学和功能信息，以阐明 体内出口通路的身体行为。使用水性血管造影的最新证据显示 插座路径中的流动模式可用于提高最低侵入性的有效性 青光眼手术（MIGS）。 PI是一名MD/PHD培训生，他建议使用Ultrahigh（〜1.3微米 组织）可见光光学相干断层扫描（Vis-OCT）的轴向分辨率无创评估 体内常规出口通路的生理学。使用获得OCT的信息，目标是 开发无创方法来评估区域流动模式并改善MIG。 Vis-Oct有能力 生成由解剖学和功能数据组成的三维体积信息。 此外，Vis-OCT使用的光的较短波长增加了其轴向分辨率，并提供 对较慢的血流和运动的敏感性提高。由于出口的任何部分都增加了电阻 途径影响出口，Vis-OCT的高分辨率将用于产生定量解剖学和 出口通路的所有部分的功能测量（小梁网，Schlemm的运河和不同 脉管系统）。这是假设通过成像产生的解剖学和功能信息 啮齿动物中的出口路径可以用作了解出口中流动模式的生物标志物 图案。为了研究这一假设，PI提案两个目的：AIM 1利用Vis-OCT进行解剖成像， 测量Schlemm的管道体积和远端脉管结构，以做出预测以发现结构 - 功能与区域出口相关。 AIM 2专注于功能指标的发展，包括 途径对小梁网中的药物干预措施和运动的响应 对眼压变化的反应，以预测区域出口。培训环境非常适合 这项投资，导师的实验室是设计OCT系统的专家 成像水出口的专家。这项研究利用了一群具有专业知识的导师 生物学，生理学，生物医学工程和临床医学。除了训练Pi成为 独立的研究人员，培训计划还应准备PI成为最大的医生之一 知识渊博的成像和将创新技术转化为临床环境。