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

青光眼是全球不可逆失明的主要原因，影响超过220万美国人。虽然升高 眼内压（IOP）是疾病发展的主要危险因素，升高眼压的机制是通过降低眼压来实现的。 眼压最终导致视神经头（ONH）的损害和神经流动功能的丧失仍不清楚。也是 尚不清楚对IOP的敏感性如何变化，以及与青光眼的其他风险因素（如年龄和种族）的相互作用。ONH是 ONH是青光眼的主要损害部位，ONH中的血流及其灌注与球后循环直接相关 已被认为在青光眼患者，特别是原发性开角型青光眼亚组中具有重要作用 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） 是目前临床上可接受的眼科成像技术。以前的OCT系统能够证明 血流在二维B扫描图像的基础上去相关和/或多普勒效应，这种能力激发最小 兴趣只有随着高速OCT系统的发展，才能足够快地获得多个3D扫描， 产生视网膜/脉络膜血管的正面图像，OCT-A在短时间内成为标准眼科检查 成像临床模式，甚至在很大程度上取代荧光素血管造影。然而，OCT的局限性在于其 由于OCT的局限性，无法对不透明巩膜组织以外的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， 甚至在光学上不可接近的区域，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基本上受到超声波衍射极限的阻碍， 导致表征深眼的精细脉管系统网络的能力较低。由于超声造影剂， 由于微泡比超声的波长小得多， 包含微泡的帧可以提供重建和映射流速和微血管的机会 密度图的分辨率比传统的超声成像提高了10倍，这被定义为超 分辨率超声微血管成像。在这个建议中，我们将开发高频超声二维阵列， 频率范围为15至20 MHz，将与完全可配置的超声成像系统接口 （Verasonics，柯克兰，WA）。新型复合平面波成像技术与三维超声的结合 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 和眼球后循环我们有三个目标：1）制作高频二维阵列，并将二维阵列与 可配置成像系统; 2）实现三维平面波成像，开发三维超分辨率超声 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 不同眼压下ONH和球后血管的血流速度。这项研究的成功将为寻求 青光眼的临床应用

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.