An all-optical photacoustic imaging system for the eye

描述(申请人提供)：这项拟议的研究将评估一种新型的全光学光声成像技术的可行性，该技术使用光折变晶体(PRC)，有可能提供超精细分辨率的视网膜、脉络膜和视神经的解剖和功能图像。视网膜亚结构的详细可视化和 视神经是评估糖尿病视网膜病变(DR)、老年性黄斑变性(AMD)和青光眼等眼科疾病的关键。然而，血管功能和局部氧输送也是疾病状态的相关指标。现有的诊断方式，如光学相干断层扫描(OCT)和超声(US)，没有提供这一信息。我们在中国实施的PAI将解决其他成像模式的缺点，同时提供亚微米图像分辨率和3至5倍于OCT的成像深度。此外，PAI还可以提供功能信息，如血红蛋白-血氧饱和度水平，这可以改善眼科疾病的临床评估。我们的方法不需要流体联轴器或美国要求的物理接触。由于所提出的PAI的全息实现使用了连续波激光和基于CCD的全场干涉术来检测光声(PA)信号，因此它潜在地可以 在500毫秒内获取3D图像数据(仅受摄像机的帧速率和PA信号检测所需带宽的限制)。这种基于电荷耦合器件的实现还便于修改视野(FOV)和分辨率，只需改变用于将光束引导到视网膜的显微镜物镜即可。通过调整人工晶状体与外部物镜之间的距离，可以获得规定的视场。原型系统的性能将使用组织模拟模体来表征。随后，我们将使用活体动物演示我们的技术描述视网膜/脉络膜微循环和视网膜色素上皮微结构的能力，以及与氧饱和度变化相关的功能变化。使用提出的方法获得的图像将与光学眼底图像和基于组织学的地面真实情况进行比较。这项拟议研究的成功完成将为开发一种多功能的眼科成像系统奠定基础，该系统可用于使用各种动物模型的临床前研究，并最终用于临床成像。

DESCRIPTION (provided by applicant): The proposed study will assess the feasibility of a novel, all-optical technique for photoacoustic imaging that employs a photorefractive crystal (PRC) and potentially can provide anatomical and functional images of the retina, choroid, and the optic nerve with ultra-fine-resolution. Detailed visualization of retinal substructures and the optic nerve is critical for evaluation of ophthalmic diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma. However, vascular function and local oxygen delivery also are relevant indicators of the diseased state. Existing diagnostic modalities such as optical coherence tomography (OCT) and ultrasound (US) do not provide this information. Our PRC-based implementation of PAI will address the shortcomings of other imaging modalities while providing sub-micron image resolution and an imaging depth that is 3 to 5 times that of OCT. Furthermore, PAI also can provide functional information such as the level of hemoglobin-oxygen saturation, which can improve clinical assessment of ophthalmic diseases. Our approach does not require fluid coupling or physical contact required by US. Because the proposed holographic implementation of PAI employs a continuous-wave laser and CCD-based full-field interferometry for detecting the photoacoustic (PA) signal, it potentially can acquire 3D-image data in 500 ms (limited only by the frame rate of the camera and the desired bandwidth for PA-signal detection). The CCD- based implementation also facilitates modification of the field of view (FOV) and resolution simply by changing the microscope objective employed to direct the optical beams to the retina. A prescribed FOV can be achieved by adjusting the distance between the ocular lens and the external objective. The performance of a prototypical system will be characterized using tissue-mimicking phantoms. Subsequently, using live animals, we will demonstrate the ability of our techniques to depict retinal/choroidal micro-circulation and the retinal-pigmented epithelium microstructure as well as functional changes related to altered oxygen saturation. Images obtained using the proposed methods will be compared with optical fundus images and histology- based ground truth. Successful completion of the proposed study will establish a basis for developing a versatile system for ophthalmic imaging that can be employed in pre-clinical research using a variety of animal models, and ultimately in clinical imaging.