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，可以快速、同步、无创地探测 3D 图像 通过光学相干断层扫描 (OCT) 和分子特异性功能获得细胞分辨率视网膜形态 自发荧光（AF）可以大大提高对年龄相关疾病的基本了解和早期诊断 相关黄斑变性（AMD）是发达国家失明的主要原因。评估和 AMD 的管理层利用多种调查方式，但 OCT 技术的进步已经 极大地有助于更好地了解该疾病，并有助于监测进展 和治疗效果。然而，由于眼睛的光学像差，传统的横向分辨率 OCT 通常限制在 10-15 µm，不足以在体内观察单个视网膜细胞。的整合 OCT 中的自适应光学 (AO) 在减轻这些像差方面取得了巨大成功。其中 在各种 AO-OCT 技术中，基于计算的 AO (CAO) 成为研究的焦点，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。眼睛的快速运动很容易扰乱反射光子的相位， 将成像限制在单个正面层。 为了克服这个问题，我们将集成快照高光谱成像方法，Image Mapping 光谱测定 (IMS)，具有全场谱域 OCT。该集成系统将实现视网膜 3D 成像 在单次相机曝光内。接下来，为了提高 3D 分辨率，我们将采用已建立的 CAO 算法 校正波前像差并将横向分辨率提高至 2 µm。由此产生的方法，我们 术语快照超高分辨率 OCT，将允许同时采集 25 万个 A 扫描。 给定典型的闪光照明持续时间 (4 µs)，等效 A 扫描速率为 62.5 GHz，大约为 比最先进的方法快三个数量级。此外，为了扩展系统的 分子成像功能，我们将添加第二个 IMS 成像通道，用于同步高光谱 视网膜色素上皮 (RPE) 自发荧光成像，实现 RPE 和 subRPE 的光谱活检 病变，例如玻璃膜疣，这是早期 AMD 的标志性病变。由此产生的双通道 OCT/AF 系统将是 第一种可以提供体内和体内视网膜结构和分子信息的成像方式 3D。我们预计这样的系统将改变 AMD 评估和管理的格局。见解如此 所获得的结果对于临床诊断和治疗具有较高的价值。此外，这样的系统将加速 转化研究，对前瞻性治疗药物进行灵敏的早期结果测试，挽救视力 从而为社会带来巨大的利益。

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.