Quantitative multimodal retinal imaging

项目摘要-摘要 我们的最终目标是开发一种用于视网膜成像的多模式VIS-OCT平台，以改善患者护理， 推进临床研究。提出了一种基于可见光的光学相干层析成像技术（VIS-OCT） 多模式多功能视网膜成像平台。两种新的基于VIS-OCT的成像技术 将建立在这个平台：定量眼底自发荧光（FAF）或VIS-OCT-FAF，和视网膜神经纤维 层（RNFL）光谱对比OCT或DUAL-OCT-RNFL。这两项新技术将增加新的工具， 眼科医生，使早期诊断和更好地监测视网膜疾病。拟议的工作是基于 这些假设得到了我们的理论模型和坚实的初步数据的有力支持。我们假设 1）绝对FAF强度的定量可以通过用以下方法标准化原始FAF信号来实现： 内部参考和外部标准荧光参考; 2）RPE OCT信号 与FAF同时获得的光谱对比度可以用作内部参考;以及 RNFL可用作由升高的IOP引起的RNFL损伤的生物标志物。三个具体目标是 提出了目的1：开发一种VIS-OCT-FAF和DUAL-OCT-RNFL成像平台。我们将 开发和完善VIS-OCT平台，包括中心波长为480 nm的VIS-OCT、中心波长为 840 nm，和FAF检测模块。具有已知荧光效率和反射率的参考目标 放置在中间视网膜成像平面中的图像将用作标准化原始数据的参考 FAF强度和定量RNFL光谱反射率。参考目标将使用PMMA载玻片染色 以A2 E为荧光分子。我们将引入A2 E当量单位（AEU）作为FAF的衡量标准。目标二： 在体模和动物中研究VIS-OCT-FAF和DUAL-OCT-RNFL成像。我们将测试该系统， 体模和动物，以验证VIS-OCT平台的能力，校准并获得反馈， 微调硬件和算法体模研究将使用含有A2 E、黑素体和TiO 2的模型眼 以模拟RPE中的脂褐素、吸收和散射。FAF图像从白化病和色素大鼠的不同 年龄将被研究。将通过质谱法对每只成像眼睛中的A2 E进行定量，以验证 FAF信号。通过对小梁网进行光凝，将在大鼠中诱导IOP升高。RNFL 将比较来自IOP增加或没有IOP增加的眼睛的光谱对比图像。目标3：学习 人类受试者中的VIS-OCT-FAF和DUAL-OCT-RNFL成像。我们的最终目标是发展一个 用于视网膜成像的多模式VIS-OCT平台，以改善患者护理并推进临床研究。 这一目标的研究将使我们能够了解系统在真实的临床环境中的行为。我们将正常的形象 6个年龄组的受试者建立基于年龄的规范数据。早期干性AMD和Stargardt's患者 疾病也将被研究。在RNFL成像研究中，我们将对6个年龄组的正常个体进行成像， 建立基于年龄的规范数据。将研究早期青光眼患者。

Project Summary-Abstract Our ultimate goal is to develop a multimodal VIS-OCT platform for retinal imaging to improve patient care and to advance clinical research. We proposed to develop a visible-light optical coherence tomography (VIS-OCT) platform for multimodal multifunctional imaging of the retina. Two novel VIS-OCT based imaging technologies will be built in this platform: quantitative fundus autofluorescence (FAF) or VIS-OCT-FAF, and retinal nerve fiber layer (RNFL) spectral contrast OCT or DUAL-OCT-RNFL. The two new technologies will add new tools for ophthalmologists to make early diagnosis and better monitor retinal diseases. The proposed work is based on hypotheses that are strongly supported by our theoretical modeling and solid preliminary data. We hypothesize that 1) Quantification of absolute FAF intensity can be achieved by normalizing raw FAF signals with an internal reference and an external standard fluorescence reference; 2) RPE OCT signals simultaneously acquired with FAF can serve as an internal reference; and 3) The spectral contrast of the RNFL can be used as a biomarker for RNFL damage by elevated IOP. Three Specific Aims are proposed. Aim 1: To develop a VIS-OCT platform for VIS-OCT-FAF and DUAL-OCT-RNFL imaging. We will develop and refine the VIS-OCT platform consisting of a VIS-OCT centered at 480 nm, a NIR-OCT centered at 840 nm, and a FAF detection module. A reference target with known fluorescence efficiency and reflectance placed in the intermediate retinal imaging plane will serve as a reference to normalize raw data to obtain absolute FAF intensity and quantitative RNFL spectral reflectance. The reference target will use a PMMA slide stained with A2E as fluorescent molecule. We will introduce the A2E equivalent unit (AEU) as a measure of FAF. Aim 2: To study VIS-OCT-FAF and DUAL-OCT-RNFL imaging in phantom and animals. We will test the system in phantom and animals to verify the capabilities of the VIS-OCT platform, to calibrate and obtain feedback for fine-tuning the hardware and algorithms. Phantom studies will use a model eye with A2E, melanosome and TiO2 to simulate lipofuscin, absorption and scattering in RPE. FAF images from albino and pigmented rats of different ages will be studied. A2E in each imaged eye will be quantified by mass-spectroscopy to verify the accuracy of FAF signals. Elevated IOP will be induced on rats by photocoagulation to the trabecular meshwork. RNFL spectral contrast images from eyes with or without increased IOP will be compared. Aim 3: To study VIS-OCT-FAF and DUAL-OCT-RNFL imaging in human subjects. Our ultimate goal is to develop a multimodal VIS-OCT platform for retinal imaging to improve patient care and to advance clinical research. Studies in this Aim will allow us to learn how the systems behave in a real clinical setting. We will image normal subjects of 6 age groups to establish age-based normative data. Patients with early dry AMD and Stargardt’s disease will also be studied. In the RNFL imaging studies, we will image 6 age groups of normal individuals to establish age-based normative data. Patients with early stage glaucoma will be studied.