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.

项目简介：青光眼是世界范围内导致不可逆性失明的主要原因。目前，唯一的 青光眼的有效治疗方法是降低眼压。从生理上讲，眼压受 房水从眼前房流出，绝大多数通过常规的 流出通道。尽管传统的流出途径很重要，但基本问题，如 远端通道对流出阻力的相对贡献及易流出区域的因素 高流量和低流量的路径仍然未知。新兴的成像方式，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，从而阐明 流出途径在体内的生理行为。最近使用房水血管造影术的证据显示 流出通道中的流动模式可以用来增加微创治疗的效果 青光眼手术(MIG)。PI是一名MD/PHD实习生，他建议利用超高(~1.3微米) 组织)轴向分辨率可见光光学相干断层扫描(VIS-OCT)无创评估 体内常规流出途径的生理学。使用为OCT获得的信息，目标是 开发非侵入性方法来评估区域流动模式并改进MIG。VIS-OCT能够 生成包含解剖数据和功能数据的三维体积信息。 此外，VIS-OCT使用的较短波长的光提高了它的轴向分辨率，并提供了 对较慢的血流和运动的敏感度增加。因为流出的任何部分阻力都增加了 途径影响流出，高分辨率的VIS-OCT将被用来产生定量的解剖和 流出道所有部分(小梁网、Schlemm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学和功能信息 啮齿类动物的流出途径可以作为了解流出途径内流动模式的生物标志物。 图案。为了研究这一假设，PI提出了两个目标：AIM 1利用VIS-OCT进行解剖成像， 测量Schlemm管体积和远端血管结构以预测发现结构性- 功能与区域外流相关。目标2侧重于功能度量的开发，包括 该通路对药物干预和小梁网运动的反应 对眼压变化的反应，以预测局部流出。培训环境非常适合 这项调查，导师实验室是设计OCT系统的专家，而共同导师实验室是 房水流出成像方面的专家。这项研究利用了一群不同的导师，他们在以下方面具有专长 生物光子学、生理学、生物医学工程和临床医学。除了训练PI成为 作为一名独立的研究人员，培训计划还应使PI准备成为最多的医生之一 具有成像和将创新技术转化为临床环境的知识。