Dynamic ICG and FA Software

描述（由申请人提供）：吲哚菁绿色（ICG）和黄绿素钠（SF）是临床上用于眼底成像的荧光染料，主要用于检测视网膜和脉络膜（视网膜后面的层）中的血管异常。它与海德堡视网膜断层扫描仪（HRT）一起使用，通过可视化电影显示染料填充和通过血管引流的动态，称为动态ICG（d-ICG）或动态血管造影（d-FA）的模式。建议开发一种新的软件技术，导致软件产品，这将有助于直接解释d-ICG和d-FA电影。第一阶段的建议集中在一个重要的临床应用-测量新生血管病变对药物治疗的反应，如阿瓦斯丁。将开发并测试一种算法，该算法提供血管充盈时间的基本测量，绘制眼底区域的充盈时间，并突出显示治疗后充盈时间的变化，以确定其显示治疗后变化的能力。第二个应用是识别供血血管，用于新生血管疾病的激光治疗。几个额外的应用程序和算法被提出，并确定为重点的主题，为以后的研究，包括第二阶段的研究。公共卫生意义：该项目的最终目标是开发一种技术，用于自动分析动态吲哚菁绿色（d-ICG）和荧光素（d-FA）血管造影片。第一阶段项目旨在展示这样做的可行性，而后期的第二阶段项目将侧重于构建和测试软件，以便为集成到产品中做好准备。该软件有许多临床和医学研究应用，包括测量对新生血管疾病药物治疗的反应，检测新生血管疾病激光治疗的供血血管，以及早期检测糖尿病视网膜病变中发生的血管变化。由于这些许多应用，有一个很好的潜在市场，使最终产品有利可图。然而，I期和II期项目将侧重于（a）临床所需和（B）可能在相对较短时间内作为可销售产品生产的应用。第二个要求（B）是关键的，因为开发和销售产品所需的时间必须很短，以便产生交付产品所需的现金流。为了满足这两个要求，焦点的第一个应用，也是在短时间内开发成可销售产品的最直接的应用，将是测量对药物治疗的反应。该产品满足这两个要求，部分原因是全球临床和医学研究迫切需要客观衡量对新血管疾病药物治疗的反应，数据集可随时用于测试原型软件，我们的专业知识使我们能够立即评估原型产品输出的图像。第一阶段的目标是证明检测药物治疗的反应是可行的。如果时间允许，其他应用程序也将在第一阶段显示为可行。具体目标是：（1）设计并实现了图像序列运动补偿算法和填充时间测量算法。填充时间是发生在参考时刻（理论上是示踪剂注入的时刻，但这很难确定，因此将使用其他参考点）和像素达到其峰值的90%的点之间的时间。(2)制作软件算法原型，测量并显示血管充盈时间的变化。(3)原型的图形用户界面（GUI）执行算法和解释所产生的测量。(4)通过处理受试者接受安维汀/抗VEGF（一种抗血管生成药物）治疗前后的图像集，测试检测治疗反应的算法。(5)只有在时间允许的情况下，一个相关的方法来识别新生血管病变中的供血血管将被原型化。

DESCRIPTION (provided by applicant): Indocyanine Green (ICG) and Sodium Fluorescein (SF) are fluorescent dyes used clinically in eye fundus imaging, primarily for detecting vascular abnormalities in the retina and choroid, which is the layer behind the retina. It is used with the Heidelberg Retinal Tomograph (HRT) by visualizing movies that show the dynamics of the dye filling and draining through the vessels, modalities called dynamic ICG (d-ICG) or dynamic Fluorescein Angiography (d-FA). It is proposed to develop a new software technology, leading to a software product, that will facilitate straightforward interpretation of d-ICG and d-FA movies. This Phase I proposal focuses, first, on an important clinical application - that of measuring the response of neovascular lesions to drug treatment, such as Avastin. An algorithm that provides a basic measurement of the filling time of blood vessels, maps that filling time over the area of the fundus, and highlights changes in the filling time following treatment, will be developed and tested for its ability to show changes after treatment. A second application is that of identifying feeder vessels, for the laser treatment of neovascular diseases. Several additional applications and algorithms are proposed and are identified as the subject of focus for later research, including the Phase II research. PUBLIC HEALTH SIGNIFICANCE: The end objective of this project is to produce technology that results in a software product for automatically analyzing dynamic Indocyanine Green (d-ICG) and Fluorescein (d-FA) angiographs. The Phase I project is aimed at showing feasibility of doing so, while the later Phase II project will be focused on building and testing the software to make it ready for integration into a product. There are many clinical and medical research applications for the software, including the measurement of response to drug treatments for neovascular conditions, the detection of feeder vessels for laser treatment of neovascular conditions, and the early detection of vascular changes that occur in diabetic retinopathy. Because of these many applications, there is a good potential market to make the end-product profitable. However, the Phase I and Phase II projects will be focused upon the application that is both (a), needed in the clinic and (b), possible to produce as a sellable product in a relatively short amount of time. The second requirement, (b), is critical because the time it takes to develop and sell a product must be short in order to produce cash flow necessary to deliver the product. To meet these 2 requirements, the first application of focus, and the most straightforward one to develop into a sellable product in a short time, will be in measuring the response to drug therapies. This product meets these two requirements partly because there is an immediate worldwide clinical and medical-research need for an objective measure of response to neovascular-disease drug therapies, data sets are readily available for testing the prototype software and our expertise equips us to assess, right away, the images output by the prototype product. The Phase I objective is to show that it is feasible to detect a response to drug therapy. If time permits, other applications will be shown to be feasible during Phase I as well. The specific aims are: (1) Design and implement algorithms for compensating the image sequences for motion and for measuring fill time. Fill time is the time that occurs between a reference instant (theoretically the instant of tracer injection, but this is difficult to determine so other reference points will be used) and the point where the pixel reaches 90% of its peak value. (2) Prototype a software algorithm that measures and displays changes in the fill time of blood vessels. (3) Prototype a graphical user interface (GUI) for executing the algorithm and interpreting the resulting measurements. (4) Test the algorithm for detecting response to treatment by processing image sets from a subject before and after treatment with Avastin/anti-VEGF, an anti-angiogenic drug. (5) Only if time permits, a related method for identifying feeder vessels in neovascular lesions will be prototyped.