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

青光眼是世界范围内导致不可逆转失明的主要原因，影响着超过220万美国人。虽然升高了 眼压(IOP)是该病发生的主要危险因素，其升高的机制 IOP最终导致视神经头(ONH)神经流动功能的损害和丧失仍不清楚。它也是 不清楚对眼压的敏感性如何变化，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是最好的 青光眼的主要损害部位和ONH中的血流及其灌注量与球后循环直接相关 已被认为在青光眼患者中起重要作用，特别是在原发性开角型青光眼的一个亚组中 和正常眼压性青光眼。目前，光学相干层析成像(OCT)及其血管成像扩展(OCT-A) 是目前临床公认的眼科成像技术。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超图像中的血流，这种能力刺激最小 利息。只有随着高速OCT系统的发展，才能以足够快的速度获取多个3D扫描 制作视网膜/脉络膜血管的正面图像，OCT-A在短时间内成为标准眼科 影像临床方式，甚至在很大程度上取代了荧光素血管造影术。然而，OCT的一个限制是它的 由于OCT的限制，无法显示超出不透明巩膜组织的ONH和眼后段 穿透力。取而代之的是，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， 即使在光学上无法接触到的区域，如ONH和眼睛的后极。然而，地物的空间分辨率 传统的逐行扫描超声成像从根本上受到超声波的衍射极限的阻碍， 从而降低了表征深部眼部细微血管网络的能力。由于超声造影剂如 由于微泡比超声波的波长小得多，所以连续超快信号的采集和定位 含有微泡的框架可以提供重建和绘制血流速度和微血管的机会 密度图的分辨率比常规超声成像提高了十倍，这被定义为超 分辨率超声微血管成像在此。在这个方案中，我们将开发高频超声2D阵列， 频率范围从15 MHz到20 MHz，将连接到完全可配置的超声成像系统 (华盛顿州柯克兰，Verasonics)。新型复合平面波成像技术与三维超声的结合 微泡定位/跟踪算法将能够为ONH提供高分辨率的微血管血流成像 和球后循环。我们的目标有三个：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，研制三维超分辨率超声 基于血流模型的微血管成像算法；3)进行兔眼体内成像，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 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.