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：青光眼是全世界不可逆转失明的主要原因。目前，唯一 青光眼的有效治疗方法是降低眼压（IOP）。生理学上，眼压受以下因素调节： 房水从眼前房流出，其中绝大多数通过传统的房水流出 流出途径。尽管传统的流出途径很重要，但诸如 远端通路对流出阻力的相对贡献以及流出区域的诱发因素 高流量和低流量的途径仍然未知。新兴的成像模式，例如光学相干 断层扫描主要用于视网膜成像，可以提供解剖和功能信息，以阐明 体内流出途径的生理行为。最近使用水性血管造影的证据表明 流出路径中的流动模式可用于提高微创治疗的有效性 青光眼手术（MIGS）。 PI 是一名 MD/PhD 实习生，他建议利用超高（~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，以无创地评估 体内常规流出途径的生理学。使用 OCT 获取的信息，目标是 开发非侵入性方法来评估区域流动模式并改善 MIGS。 Vis-OCT 能够 生成由解剖数据和功能数据组成的三维体积信息。 此外，vis-OCT 使用的光波长较短，可提高其轴向分辨率并提供 对较慢的血流和运动的敏感性增加。由于流出的任何部分的阻力增加 通路影响流出，vis-OCT 的高分辨率将用于生成定量的解剖学和 流出通路所有部分（小梁网、施莱姆氏管和远端）的功能测量 脉管系统）。因此，假设通过成像产生的解剖和功能信息 啮齿动物的流出通路可以作为生物标志物，用于了解流出物内的流动模式 图案。为了研究这一假设，PI 提出了两个目标：目标 1 利用 vis-OCT 进行解剖成像， 测量施累姆管体积和远端脉管系统结构以进行预测以发现结构- 功能与区域流出相关。目标 2 侧重于功能指标的开发，包括 通路对药物干预的反应和小梁网的运动 反应眼压变化，预测区域流出。培训环境非常适合 本次调查中，导师实验室是设计 OCT 系统的专家，共同导师实验室是 房水流出成像专家。这项研究利用了具有专业知识的多元化导师群体 生物光子学、生理学、生物医学工程和临床医学。除了培训 PI 成为 作为一名独立研究员，培训计划还应让 PI 成为最有能力的医生之一。 精通成像并将创新技术转化为临床环境。