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

项目摘要：一种成像模式，允许快速，同时，非侵入性探测3D 通过光学相干断层扫描（OCT）和分子特异性功能的细胞分辨率视网膜形态学 通过自体荧光（AF）可以大大提高对年龄的基本理解和早期诊断， 黄斑变性（AMD）是发达国家致盲的主要原因。评价和 AMD的管理利用了几种研究模式，但OCT技术的进步 显著有助于更好地了解疾病，并有助于监测进展 和治疗效果。然而，由于眼睛的光学像差，传统的光学成像系统的横向分辨率会降低。 OCT通常限于10-15 µm，不足以在体内可视化单个视网膜细胞。的整合 将自适应光学（AO）引入OCT中已经证明在减轻这些像差方面取得了巨大成功。之间 在各种AO-OCT技术中，基于计算的AO（CAO）成为研究的热点，因为它表明 在数据后处理灵活性和降低系统成本方面具有独特的优势。然而，CAO非常 对相位稳定性敏感。眼睛的快速运动可以很容易地扰乱反射光子的相位， 将成像限制到单个正面层。 为了克服这一问题，我们将结合快照高光谱成像方法，图像映射 光谱仪（IMS），具有全视场光谱域OCT。集成系统将实现视网膜的3D成像 在一个单一的相机曝光。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 µm。结果方法，我们 快照超高分辨率OCT将允许同时采集25万次A扫描。 给定典型的闪光灯照明持续时间（4 µs），等效A扫描速率为62.5 GHz，约为 比最先进的方法快三个数量级。此外，为了扩大系统的 功能的分子成像，我们将增加第二个IMS成像通道，同时高光谱 视网膜色素上皮（RPE）自体荧光成像，实现RPE和subRPE的光谱活检 病变如玻璃疣，早期AMD的标志性病变。由此产生的双通道OCT/AF系统将是 第一成像模态，其可以提供关于视网膜在体内和在体外的结构和分子信息。 3D.我们设想这样一个系统将改变AMD评估和管理的格局。这些见解 具有较高的临床诊断和治疗价值。此外，这样的系统将加速 转化研究，对前瞻性治疗药物进行敏感和早期结果测试，挽救视力 从而为社会带来巨大的效益。

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.