Imaging the functional biomarker of photoreceptors

项目摘要-摘要 “视觉是我们最基本的感官，当失明夺走时，它可能是最大的悲剧。 我们对这种形式的理解“。光感受器是启动视觉的光探测细胞。光感受器的丢失导致损失 远见卓识。这种情况发生在数百万患有遗传性视网膜变性或老年性黄斑的美国人身上 退行性变(AMD)。失明不仅是个人的悲剧，也是社会的负担。它是 估计一名视网膜色素变性(RP)患者的平均医疗费用为7000美元/年，甚至更多 与年龄相匹配的非RP患者相比有显著差异。我们想要开发三种新的活体成像技术 定位视紫红质，视紫红质是杆状感光细胞的功能和解剖生物标记物。基于我们的深入研究 分析目前和不久的将来对监测大脑皮质功能和解剖的临床需求 光感受器，我们相信它将改变诊断、监测和治疗评估的游戏规则 用于视网膜退行性疾病，包括遗传性视网膜变性、AMD等疾病。这 应用具有以下假设：1、可见光OCT(VIS-OCT)提供深度分辨信息 用于分割以准确测量视紫红质的水平和分布；2、视紫红质的量 可以通过测量位于视紫红质中的不同波长的吸光度来计算 吸收光谱；3、基于VIS-OCT技术的成像设备可以为 评估患者视紫红质的水平和分布。这项提议有三个具体目标。在目标1中，我们 将开发和完善三种基于VIS-OCT的成像技术：具有中心的单波段VIS-OCT 波长520 nm，接近视紫红质的峰值吸收；三波段VIS-OCT，使用三个波段 探测跨越视紫红质吸收光谱的光；以及使用连续的 覆盖视紫红质吸收波长从520 nm到580 nm的光谱。单频技术 将对视网膜成像两次，一次是暗适应，然后是光适应。使用三频和宽带VIS- OCTS视紫红质含量将根据同时采集的OCT图像基于 视紫红质在不同波长的摩尔消光系数不同。因为三频和宽带- 波段技术只需要在暗适应状态下对视网膜成像一次，这将更具临床意义 很友好。在目标2中，我们将使用动物模型来测试和微调这三个VIS-OCT。在目标3中，我们将测试 三个OCT系统在人类受试者中提供重要反馈，以改进和微调硬件和 软件，并建立正常视网膜和不同疾病阶段的视网膜的视紫红质范围。我们 预计在该项目结束时，这三个系统将在临床上就绪。圆满完成 拟议的实验将为眼科临床护理视网膜患者增加一项强大的技术 退行性疾病。

Project Summary-Abstract “Vision is the most fundamental of our senses and it is perhaps the greatest tragedy of all when blindness robs us of this modality”. Photoreceptors are light-detecting cells initiating vision. Loss of photoreceptor leads to loss of vision. This happens in millions of Americans with hereditary retinal degenerations or age-related macular degeneration (AMD). Loss of vision is not only a personal tragedy but also a burden to the society. It is estimated that a patient with retinitis pigmentosa (RP) has an average health care cost of $7,000/year, more than that of age-matched non-RP patients. We want to develop three new in vivo imaging technologies for mapping rhodopsin, the functional and anatomic biomarker of rod photoreceptors. Based on our in-depth analysis of the clinical needs of today and in the near future for monitoring the function and anatomy of photoreceptors, we believe it will be a game changer for the diagnosis, monitoring, and treatment evaluation for retinal degenerative disorders, including hereditary retinal degeneration, AMD, and other diseases. This application has the following hypotheses: 1, Visible-light OCT (VIS-OCT) provide depth resolved information for segmentation to measure the levels and distribution of rhodopsin accurately; 2, The amount of rhodopsin can be calculated from measurements of absorbance at different wavelengths located in the rhodopsin absorption spectrum; 3, Imaging devices based on the VIS-OCT technologies could provide information to assess the levels and distribution of rhodopsin in patients. This proposal has three Specific Aims. In Aim 1, We will develop and refine three VIS-OCT based imaging technologies: a Single-Band VIS-OCT with a center wavelength of 520 nm close to the peak absorption of rhodopsin; a Tri-Band VIS-OCT that uses three bands of probing light spanning the rhodopsin absorption spectrum; and a Broad-Band VIS-OCT that uses a continuous spectrum covering the rhodopsin absorption wavelengths from 520 nm to 580 nm. The Single-Band technology will image the retina twice, once dark-adapted and then light adapted. With the Tri-Band and Broad-Band VIS- OCTs rhodopsin content will be calculated from the simultaneously acquired OCT images based on the different molar extinction coefficients of rhodopsin at different wavelengths. Since the Tri-Band and Broad- Band technologies only need to image the retina once in the dark-adapted state, it would be much more clinical friendly. In Aim 2, we will use animal models to test and fine-tune the three VIS-OCTs. In Aim 3, we will test the three OCT systems in human subjects to provide vital feedback to improve and fine-tune the hardware and software, and to establish rhodopsin ranges of normal retina and retinas of different stages of diseases. We expect to have the three systems clinically ready by the end of this project. Successful completion of the proposed experiments would add a powerful technology to ophthalmology clinics for care of patient with retinal degenerative diseases.