High-Resolution Flow Imaging of Optic Nerve Head and Retrolaminar Microvascular Circulation

视神经乳头和层后微血管循环的高分辨率血流成像

• 批准号: 10649225
• 负责人: Shigao Chen
• 金额: $ 73.91万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649225
• 关键词: 3-Dimensional; 3D ultrasound; Adoption; Affect; Age; Aging; Algorithms; American; Angiography; Area; Blindness; Blood; Blood Vessels; Blood flow; Brain; Calibration; California; Characteristics; Circulation; Clinic; Clinical; Color; Contrast Media; Development; Disease; Disease Progression; Doppler Effect; Doppler Ultrasound; Electric Stimulation; Eye; Fluorescein Angiography; Frequencies; Gender; Generations; Glaucoma; Head; Image; Imaging technology; Lead; Maps; Measurement; Methods; Microbubbles; Microcirculation; Microscopy; Modality; Morphology; Ophthalmologist; Ophthalmology; Optic Disk; Optical Coherence Tomography; Optics; Oryctolagus cuniculus; Patient Care; Patients; Penetration; Perfusion; Persons; Physiologic Intraocular Pressure; Posterior eyeball segment structure; Primary Open Angle Glaucoma; Quantitative Evaluations; Race; Research; Research Personnel; Resolution; Resources; Risk Factors; Role; Scanning; Scientist; Sclera; Site; Speed; Subgroup; System; Techniques; Technology; Tissues; Ultrasonic Transducer; Ultrasonic wave; Ultrasonics; Ultrasonography; United States National Institutes of Health; Universities; Visualization; aging population; clinical application; clinical imaging; clinical practice; density; elastography; experience; imaging system; improved; in vivo; interest; medical schools; neural; novel; optical imaging; radiologist; recruit; retina blood vessel structure; retinal imaging; risk stratification; success; superresolution imaging; tool; two-dimensional; ultra high resolution; ultrasound

Glaucoma is a leading cause of irreversible blindness worldwide, affecting over 2.2 million Americans. Although elevated intraocular pressure (IOP) is the primary risk factor for the development of the disease, the mechanisms by which elevated IOP eventually leads to damage and loss of neural flow function for optic never head (ONH) are still unclear. It is also unclear how sensitivity to IOP varies and interacts with other risk factors for glaucoma, such as aging and race. ONH is the principal site of damage in glaucoma, and the blood flow in the ONH and its perfusion directly related retrobulbar circulation have been recognized as an important role in glaucoma patients, particularly in a subgroup of primary open-angle glaucoma and normal-tension glaucoma. Currently, optical coherence tomography (OCT) and its angiographic extension (OCT-A) are, at present, clinically accepted technologies for ophthalmic imaging. Previous OCT systems were able to demonstrate blood-flow in two-dimensional B-scan images based on decorrelation and/or Doppler effects, this capability excited minimal interest. It was only with the development of high-speed OCT systems that could acquire multiple 3D scans fast enough to produce en-face images of the retinal/choroidal vasculature that OCT-A became in short order a standard ophthalmic imaging clinical modality, even replacing fluorescein angiography to a great extent. A limitation of OCT, however, it is its inability to image ONH and posterior segment of eye that beyond the opaque sclera tissue due to limitation of OCT penetration. Instead, ultrasound color Doppler methods have long offered a means for visualizing and characterizing flow, even in optically inaccessible areas such as the ONH and posterior pole of the eye. However, the spatial resolution of conventional line-by-line scan ultrasound imaging is fundamentally hindered by the diffraction limit of the ultrasound wave, resulting in less ability to characterize the fine vasculature network of the deep eye. Since ultrasound contrast agents such as microbubble are much smaller than the wavelength of ultrasound, acquisition and localization of successive ultrafast frames containing microbubbles may provide an opportunity to reconstruct and map both flow velocity and microvessel density map with a ten-fold resolution improvement than conventional ultrasound imaging, which is defined as super- resolution ultrasound microvessel imaging herein. In this proposal, we will develop high frequency ultrasonic 2D array with frequencies in the range from 15 to 20 MHz which will be interfaced to a fully configurable ultrasound imaging system (Verasonics, Kirkland, WA). The combination of novel compounding plane wave image technology and 3D ultrasound microbubble localization/tracking algorithm will be able to provide high-resolution microvessel blood flow imaging of ONH and retrobulbar circulation. We have three aims: 1) Fabricate high-frequency 2D array and integrate 2D array with configurable imaging system; 2) Implement 3D plane-wave imaging and develop 3D super-resolution ultrasound microvessel imaging algorithm using flow phantoms; 3) Conduct in vivo rabbit eye imaging to assess blood density and flow velocity on ONH and retrobulbar vessels with different IOPs. Success of this study will pave the way towards pursuing clinical application of Glaucoma.

青光眼是全球不可逆转失明的主要原因，影响超过 220 万美国人。虽然升高了 眼内压（IOP）是该疾病发生的主要危险因素，眼压升高的机制 IOP最终导致视神经乳头（ONH）损伤和神经流功能丧失尚不清楚。这也是 目前尚不清楚对眼压的敏感性如何变化以及与其他青光眼危险因素（例如衰老和种族）的相互作用。 ONH 是 青光眼损伤的主要部位，ONH的血流及其灌注直接与球后循环相关 已被认为在青光眼患者中发挥重要作用，特别是在原发性开角型青光眼亚组中 和正常眼压性青光眼。目前，光学相干断层扫描（OCT）及其血管造影扩展（OCT-A） 是目前临床上接受的眼科成像技术。以前的 OCT 系统能够证明 基于去相关和/或多普勒效应的二维 B 扫描图像中的血流，此功能激发了最小的 兴趣。只有高速 OCT 系统的发展才能足够快地获取多个 3D 扫描 生成视网膜/脉络膜脉管系统的正面图像，OCT-A 很快就成为眼科标准 影像学临床模式，甚至在很大程度上取代荧光素血管造影。然而 OCT 的局限性在于 由于 OCT 的限制，无法对不透明巩膜组织之外的 ONH 和眼后段进行成像 渗透。相反，超声彩色多普勒方法长期以来提供了一种可视化和表征血流的方法， 即使在光学无法到达的区域，例如 ONH 和眼睛的后极。然而，空间分辨率 传统的逐行扫描超声成像从根本上受到超声波衍射极限的阻碍， 导致表征深部眼部精细脉管系统网络的能力较差。由于超声造影剂如 由于微泡比超声波的波长小得多，因此连续超快的采集和定位 包含微泡的帧可以提供重建和绘制流速和微血管的机会 密度图的分辨率比传统超声成像提高十倍，被定义为超 本文中的分辨率超声微血管成像。在本提案中，我们将开发高频超声波二维阵列 频率范围为 15 至 20 MHz，将连接到完全可配置的超声成像系统 （Verasonics，华盛顿州柯克兰）。新型复合平面波图像技术与3D超声的结合 微泡定位/跟踪算法将能够提供ONH的高分辨率微血管血流成像 和球后循环。我们有三个目标：1）制造高频二维阵列并将二维阵列与 可配置的成像系统； 2）实现3D平面波成像并开发3D超分辨率超声 使用流动体模的微血管成像算法； 3) 进行体内兔眼成像以评估血液密度和 ONH 和球后血管在不同 IOP 下的流速。这项研究的成功将为追求目标铺平道路 青光眼的临床应用。