Elastographic Imaging of the Retina/Choroid in Age-Related Macular Degeneration

描述（由申请人提供）：年龄相关性黄斑变性（AMD）是一种视网膜色素上皮疾病，其特征是蛋白质/脂质沉积（drusen）、地理萎缩和新生血管。目前用于AMD诊断成像的技术包括吲哚菁绿染料或荧光素血管造影、自身荧光成像和光学相干断层扫描（OCT）。OCT图像描述由局部光学折射率变化引起的光学后向散射。OCT提供的高分辨率已被证明对AMD相关的结构变化的成像是非常宝贵的。然而，我们对这种疾病的病理生物学的理解是不确定的。不依赖于光散射的高分辨率视网膜/脉络膜成像模式的发展为获得对AMD疾病过程、早期诊断和临床管理的新见解提供了潜在的手段。在这个项目中，我们建议开发和测试成像视网膜/脉络膜弹性特性的方法，通过检测由声辐射力引起的这些结构内产生的微小位移。这种在布鲁氏膜和脉络膜水平上的弹性变化是由于水肿沉积和微血管模式改变的结果。此外，组织弹性变化也与新生血管的形成有关。成像弹性改变的能力可能提供一种方法来可视化与AMD疾病进展相关的病理改变的前体。我们建议使用高速，高分辨率，增强深度OCT对视网膜/脉膜成像，并在安全的诊断水平下观察暴露于声辐射力时发生的微小位移。我们将利用两种技术：声辐射力脉冲成像（ARFI）成像，其中位移是由短暂的（1毫秒量级）脉冲引起的，以及振动声学，其中位移是由两个频率略有不同的超声波源相互作用引起的低频（1千赫量级）振动引起的。研究将在组织幻影、兔眼、AMD灵长类动物模型以及正常和AMD人类受试者中进行，我们将证明视网膜/脉络膜弹性特性的改变与特定病理条件相关，包括萎缩性视网膜、地理性萎缩和新生血管。

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is a disease of the retinal pigment epithelium characterized by the appearance of protein/lipid deposits (drusen), geographic atrophy and neovascularization. Techniques currently used for diagnostic imaging of AMD include indocyanine green dye or fluorescein angiography, autofluorescence imaging and optical coherence tomography (OCT). OCT images depict optical backscatter, caused by variation in local optical refractive index. The high resolution provided by OCT has proved invaluable for imaging structural changes associated with AMD. Nevertheless, our understanding of the pathobiology of this disease is uncertain. The development of high-resolution retinal/choroidal imaging modalities not dependent upon optical scattering offers a potential means for gaining new insights into the AMD disease process, early diagnosis and clinical management. In this project we propose to develop and test means for imaging the elastic properties of the retina/choroid by detection of minute displacements generated within these structures induced by acoustic radiation force. Such elastic changes at the level of Bruch's membrane and the choroid would be expected as a consequence of drusen deposition and altered microvascular patterns. Furthermore, tissue elastic changes are also known to be associated with the development of neovascularization. A capacity to image elastic alteration may provide a means to visualize precursors to pathologic changes associated with AMD disease progression. We propose to image the retina/choroid with high speed, high-resolution, enhanced-depth OCT and to observe minute displacements occurring upon exposure to acoustic radiation force at safe, diagnostic levels. We will utilize two techniques: acoustic radiation force impulse (ARFI) imaging, in which displacements are induced by a brief (order of 1 msec) impulse, and vibro-acoustography, in which displacements are induced by low-frequency (order of 1 kHz) vibrations induced by interaction of two ultrasound sources of slightly different frequency. Studies will be conducted with tissue phantoms, rabbit eyes, in a primate model of AMD and finally normal and AMD human subjects in which we will demonstrate alterations in retinal/choroidal elastic properties associated with specific pathologic conditions including drusen, geographic atrophy, and neovascularization.