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

描述（由申请人提供）：视网膜相关性黄斑变性（AMD）是一种视网膜色素上皮疾病，其特征在于出现蛋白质/脂质沉积物（玻璃疣）、地图状萎缩和新生血管形成。目前用于AMD诊断成像的技术包括吲哚菁绿色染料或荧光素血管造影术、自体荧光成像和光学相干断层扫描（OCT）。OCT图像描绘了由局部光学折射率的变化引起的光学反向散射。OCT提供的高分辨率已被证明对于与AMD相关的成像结构变化是非常宝贵的。然而，我们对这种疾病的病理生物学的理解是不确定的。不依赖于光学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手段，通过检测这些结构内产生的微小位移引起的声辐射力的视网膜/脉络膜的弹性特性成像。在布鲁赫膜和脉络膜水平的这种弹性变化将被预期为玻璃疣沉积和改变的微血管模式的结果。此外，还已知组织弹性变化与新血管形成的发展相关。成像弹性改变的能力可以提供一种手段来可视化与AMD疾病进展相关的病理变化的前兆。我们建议用高速、高分辨率、增强深度OCT对视网膜/脉络膜成像，并观察在安全诊断水平下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（ARFI）成像，其中位移是由一个简短的（1毫秒的顺序）脉冲，和振动声成像，其中位移是由低频（1 kHz的顺序）振动引起的两个超声源的相互作用引起的略有不同的频率。将在AMD的灵长类动物模型中用组织幻影、兔眼以及最终的正常和AMD人类受试者进行研究，其中我们将证明与特定病理状况相关的视网膜/脉络膜弹性特性的改变，包括玻璃疣、地图状萎缩和新血管形成。

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.