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，其特征是出现蛋白质/脂肪沉积(玻璃疱疹)、地理性萎缩和新生血管。目前用于AMD诊断成像的技术包括吲哚青绿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图像描述了由局部光学折射率变化引起的光学后向散射。事实证明，OCT提供的高分辨率对于AMD相关的结构变化成像是非常宝贵的。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AMD疾病过程、早期诊断和临床治疗提供了潜在的手段。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，通过检测声辐射力在这些结构中产生的微小位移来进行成像。布鲁赫膜和脉络膜水平的这种弹性变化是玻璃疣沉积和微血管模式改变的结果。此外，已知的组织弹性变化也与新生血管的发展有关。成像弹性改变的能力可以提供一种方法来可视化与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、增强深度的OCT成像视网膜/脉络膜，并观察在安全的诊断水平上暴露于声辐射力时发生的微小移位。我们将利用两种技术：声辐射力脉冲(ARFI)成像和振动-声学成像，在ARFI成像中，由短暂(1毫秒量级)脉冲产生位移，在振动声学成像中，由两个频率略有不同的超声源相互作用引起的低频(1 kHz量级)振动引起位移。我们将在AMD的灵长类动物模型中进行组织幻影、兔眼，最后是正常人和AMD人类受试者的研究，在这些研究中，我们将展示与特定病理条件相关的视网膜/脉络膜弹性特性的变化，包括玻璃体、地理萎缩和新生血管。

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.