High-resolution Elastographic Assessment of the Optic Nerve Head

摘要 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。与 随着人口老龄化，预计到2020年青光眼患者人数将达到8000万 全世界有11个双盲患者。本研究的目的是开发一种新的成像和测量工具， 非侵入性地测量视神经乳头（ONH）和筛板（LC）的弹性。为了实现这一目标， 我们建议使用相位分辨OCT来检测由声辐射力引起的小位移 (ARF)在ONH。我们进一步提出了一种新型的单晶二维阵列工作在4~10 MHz的范围内 以产生ARF推力。我们建议使用单晶超声换能器， 灵敏度组合系统将使我们能够生成描绘局部位移的图像， 纳米分辨率使用最先进的数值模型，这些数据将与复杂的 组织宏观和微观结构，以确定组织的各向异性、不均匀弹性特性 具有高分辨率和高灵敏度。这将使我们能够详细描述该协会 年龄、种族和性别对ONH组织力学性能的影响。我们的具体目标是： 具体目标1：开发用于ARF推力生成的单晶2D超声阵列。 具体目标2：开发集成的2D阵列ARF-光学相干弹性成像（OCE）系统， 可实现OCT、US和ARF-OCE共配准成像。 具体目标3：开发和验证数字模型，将目标1和 2测定LC和ONH的局部力学性能。 具体目标4：对人尸体和兔眼进行离体弹性成像，以确定其能力 并评估ARF-OCE系统检测ONH和LC组织特性变化的性能 与年龄、性别和物种有关。在人类眼中，我们也会确定由于种族或 疾病和ONH地区之间。 具体目标5：通过在兔眼中对LC和ONH进行体内成像，证明临床前成像能力 使用ARF-OCE系统和优化系统进行体内成像。

Abstract Glaucoma is a leading cause of irreversible blindness worldwide, affecting over 2.2 million Americans. With an aging population, it is estimated that by 2020 the number of people suffering glaucoma will reach 80 million worldwide, with 11 bilaterally blind. The goal of this study is to develop a novel tool for imaging and measuring elastic properties of the optic nerve head (ONH) and lamina cribrosa (LC) non-invasively. To address this goal, we propose to use phase-resolved OCT to detect small displacements induced by acoustic radiation force (ARF) in the ONH. We further propose to build a novel single crystal 2D array operating in the 4~10 MHz range to generate the ARF pushing force. We propose to use single crystal ultrasound transducers for increased sensitivity. The combined system will enable us to generate images depicting local displacements with nanometer resolution. Using state-of-the-art numerical models this data will be integrated with the complex tissue macro and microstructure to determine the anisotropic, inhomogeneous elastic properties of the tissues of the ONH with high resolution and sensitivity. This will allow us to characterize in detail the association between age, race and gender on the mechanical properties of the tissues of the ONH. Our Specific Aims are: Specific Aim 1: Develop single crystal 2D ultrasound array for ARF pushing force generation. Specific Aim 2: Develop an integrated 2D array ARF-Optical coherence elastography (OCE) system that enables coregistered OCT, US, and ARF-OCE imaging. Specific Aim 3: Develop and validate numerical models that integrate the experimental data from Aims 1 and 2 to determine the local mechanical properties of the LC and ONH. Specific Aim 4: Conduct ex-vivo elastography of human cadaveric and rabbit eyes to establish the capability and assess the performance of the ARF-OCE system to detect changes in ONH and LC tissue properties associated with age, gender and species. In human eyes, we will also determine differences due to race or disease and between regions of the ONH. Specific Aim 5: Demonstrate preclinical imaging capability with in-vivo imaging of LC and ONH in rabbit eyes using ARF-OCE system and optimize system for in-vivo imaging.