A Snapshot Adaptive Optics and Hyperspectral Autofluorescence Fundus Camera for Age-Related Macular Degeneration (AMD)

项目摘要：一种成像方式，允许快速、同时、非侵入性地对两者进行3D探测 光学相干断层扫描(OCT)的细胞分辨率、视网膜形态和分子特异性功能 通过自发荧光(AF)可以显著提高对年龄的基本认识和早期诊断 相关性黄斑变性(AMD)是发达国家导致失明的主要原因。评估和 AMD的管理使用了几种调查模式，但OCT技术的进步 大大有助于更好地了解这种疾病，并有助于监测进展 和治疗效果。然而，由于眼睛的光学像差，常规光学系统的横向分辨率 OCT通常限制在10-15微米，不足以显示活体中的单个视网膜细胞。整合了 将自适应光学(AO)引入OCT已证明在减轻这些像差方面取得了巨大成功。其中 各种声光OCT技术，基于计算的声光(CAO)技术因其显示出的信息而成为研究的热点 在数据后处理灵活性和降低系统成本方面具有独特优势。然而，CAO非常 对相稳定性敏感。眼睛的快速运动很容易扰乱反射光子的相位， 将成像限制在单个面层。 为了克服这个问题，我们将整合一种快照高光谱成像方法--图像映射 光谱(IMS)，全场光谱域OCT。集成系统将使视网膜的3D成像成为可能 在一次相机曝光中。接下来，为了提高3D分辨率，我们将采用已建立的CAO算法 以校正波前像差并将横向分辨率提高到2微米。我们所得到的方法 Term Snapshot超高分辨率OCT，将允许同时收购25万个A扫描。 在给定典型闪光灯照明持续时间(4微米S)的情况下，等效A扫描率为62.5 GHz，这大约是 比最先进的方法快三个数量级。此外，为了扩大系统的 为了增强分子成像的功能，我们将为同步高光谱增加第二个IMS成像通道 视网膜色素上皮(RPE)自发荧光成像，使RPE和亚RPE能够进行光谱活检 早期AMD的标志性病变，如玻璃斑疹。由此产生的双通道OCT/AF系统将是 第一种成像方式，可以提供关于活体和非视网膜的结构和分子信息 3D。我们设想这样一个系统将改变AMD评估和管理的格局。这些洞察力是这样的 所得结果在临床诊断和治疗中具有较高的价值。此外，这样的系统将加速 对预期治疗药物进行敏感和早期结果测试的转化性研究，挽救视力 从而为社会提供了巨大的利益。

Project Summary: An imaging modality that allows for fast, simultaneous, noninvasive probing of both 3D cellular resolution retinal morphology by optical coherence tomography (OCT) and molecular-specific functions by autofluorescence (AF) could substantially improve both basic understanding and the early diagnosis of age- related macular degeneration (AMD), the leading cause of blindness in the developed world. The evaluation and management of AMD utilize several investigation modalities, but advancements in OCT technology have significantly contributed to better understanding of the disease, and have helped with monitoring progression and therapeutic efficacy. However, due to optical aberrations of the eye, the transverse resolution of conventional OCT is generally limited to 10-15 µm, inadequate for visualizing individual retinal cells in vivo. The integration of adaptive optics (AO) into OCT has demonstrated an immense success in mitigating these aberrations. Among various AO-OCT techniques, computation-based AO (CAO) becomes the spotlight of research because it shows unique advantages in data postprocessing flexibility and a reduced system cost. However, CAO is extremely sensitive to phase stability. The rapid motion of the eye can easily scramble the phase of reflected photons, restricting imaging to a single en-face layer. To overcome this problem, we will integrate a snapshot hyperspectral imaging method, Image Mapping Spectrometry (IMS), with full-field spectral-domain OCT. The integrated system will enable 3D imaging of retina within a single camera exposure. Next, to improve resolution in 3D, we will adapt an established CAO algorithm to correct for wavefront aberrations and improve transverse resolution to 2 µm. The resultant method, which we term snapshot ultra-high-resolution OCT, will allow an acquisition of a quarter million A-scans simultaneously. Given a typical flash illumination duration (4 µs), the equivalent A-scan rate is 62.5 GHz, which is approximately three orders of magnitude faster than the state-of-the-art methods. Furthermore, to expand the system’s functionality to molecular imaging, we will add a second IMS imaging channel for simultaneous hyperspectral imaging of retinal pigment epithelium (RPE) autofluorescence, enabling spectral biopsy of the RPE and subRPE lesions such as drusen, the hallmark lesion of early AMD. The resultant dual-channel OCT/AF system will be the first imaging modality that can provide both structural and molecular information about the retina in vivo and in 3D. We envision such a system would shift the landscape of AMD evaluation and management. The insights so obtained will be of high value in clinical diagnosis and treatment. In addition, such a system will accelerate translational research with sensitive and early outcome testing of prospective therapeutic agents, saving sight and thereby providing enormous benefit to society.