ShEEP Request for Upgrade to Retinal Optical Coherence Tomography Instrumentation

此共享设备评估计划(SHEEP)应用程序要求对 现有的多模式超高分辨率视网膜光学相干层析成像(OCT)仪器 该仪器将大大增强现有视网膜变性研究的技术潜力，并 允许开展与现有文书难以或不可能实现的合作。 现有的仪器虽然功能强大，但技术陈旧，只能进行面部成像和b型扫描。 横断面成像，数据分析是乏味和缓慢的，虽然最初对我们的 2011年成立的研究小组，它不再激励研究回答以下类型的研究问题 在当代临床前视网膜研究中至关重要。视网膜检查中的挑战之一是使 在相同的视网膜体积元素中进行多项测量。这可以包括，例如，OCT测量 节段性视网膜层厚度，评估特定细胞类型(例如，光感受器)的活力，而 同时评估成像的视网膜的哪个区域被病毒载体转导，以便确定 载体的治疗货物是否成功挽救了视网膜变性，或者， 增加了毒性。此次升级将在标准超高分辨率OCT的基础上增加六种模式。 包括：1)眼底照相，2)眼底自发荧光，3)任意眼底荧光 荧光，4)荧光素血管造影术，5)血管造影术-OCT，和6)自适应光学。所有额外的 医疗模式将完全集成到现有的UHR OCT平台中，并使用一些先前存在的架构 升级。此次升级将极大地帮助多个项目。沙利文实验室(IDEA冠军)将 直接受益于拥有多模式OCT机器，该机器可解决临床前基因治疗中的关键变量 研究(退伍军人事务部和美国国立卫生研究院支持)，例如，可以量化视网膜外治疗救援 与视网膜外细胞病毒载体转导的确切测量区域相关。飞斯勒实验室将 直接受益于多模式OCT机器，该机器可以评估视网膜外部变性和血管 眼冲击伤中可能发生的损伤。冯实验室将受益于使用增强的仪器 这可以阐明与帕金森氏病相关的特定基因突变对 啮齿动物视网膜的显微解剖和功能以及与沙利文实验室合作开发和测试基因 视网膜帕金森病的治疗。Russo实验室对Eyes感兴趣，将其作为调查 由超强毒力肺炎克雷伯菌引起的眼睛内的全身性感染 并识别致病性变量并采取措施制定新的治疗策略。特罗恩实验室是 对衰老和新陈代谢以及黄斑变性和糖尿病视网膜病变感兴趣 与沙利文实验室合作研究疾病机制和发展的机会 新的治疗方法。综上所述，升级的多模式视网膜成像系统将在 加强临床前基因治疗策略的技术途径，加强理解 孤儿遗传性视网膜外变性与常见AMD和糖尿病视网膜病变的机制会的 在现有协作的基础上建立，并开始使用视网膜作为 进入其他退伍军人相关疾病州的跳板，这些州是其他优秀退伍军人管理局调查人员的重点。 多模式视网膜成像系统升级也将作为学生和下一代的培训工具 新一代调查人员。

This Shared Equipment Evaluation Program (ShEEP) application requests a state-of-the-art Upgrade of an existing Ultrahigh resolution Retinal Optical Coherence Tomography (OCT) instrument to a Multi-Modality instrument that will substantially enhance the technological potential of existing retinal degeneration studies and allow the development of collaborations which were difficult or impossible to achieve with the existing instrument. The existing instrument, while functional, is old technology and is only capable of en face imaging and b-scan cross sectional imaging, the data analysis is tedious and slow, and while initially highly competitive for our research group in 2011, it no longer incentivizes research to answer the type of research questions that are critical in the contemporary preclinical retinal studies. One of the challenges in retinal investigations is to make multiple measures in the same retinal volume elements. This can include, for example, OCT measures of segmented retinal layer thicknesses that assess the vitality of a particular cell type (e.g., photoreceptors) while simultaneously evaluating which area of the imaged retina was transduced by a viral vector, in order to determine whether the therapeutic cargo of the vector succeeded in rescuing retinal degeneration or, alternatively, promoted toxicity. The Upgrade will add six additional modalities to the standard ultrahigh resolution OCT. These include: 1) Fundus photography, 2) Fundus Autofluorescence, 3) Fundus Fluorescence for Arbitrary Fluors, 4) Fluorescein Angiography, 5) Angiographic-OCT, and 6) Adaptive Optics. All of the additional modalities will fully integrate into existing UHR OCT Platform and use some of the preexisting architecture in the Upgrade. Multiple projects will be greatly assisted by the Upgrade. The Sullivan Lab (idea champion) will directly benefit by having a multimodal OCT machine that addresses critical variables in preclinical gene therapy studies (VA and NIH supported), for example, where quantitation of outer retinal therapeutic rescue can be correlated with definitive measured areas of outer retinal cellular viral vector transduction. The Fliesler Lab will directly benefit with a multimodal OCT machine that can assess outer retinal degeneration as well as vascular injury as may occur in Ocular Blast Trauma. The Feng Lab will benefit with access to enhanced instrumentation that can elucidate the impact of mutations in specific genes causally associated with Parkinson’s Disease on the microanatomy and function of the rodent retina and collaboration with the Sullivan Lab to develop and test gene therapeutics for PD in the retina. The Russo Lab is interested in the eye as a site to investigate the establishment of systemic infection the focalizes within the eye that is due to hypervirulent Klebsiella pneumonia and to discern pathogenicity variables and take steps to novel therapeutic strategies. The Troen Lab is interested in aging and metabolism and the diseases of macular degeneration and diabetic retinopathy offer opportunities for collaboration with the Sullivan Lab to investigate mechanisms of disease and the development of novel therapeutics. In Summary, the Upgrade Multimodal Retinal Imaging System will be greatly useful in strengthening the technological approaches to preclinical gene therapy strategies, to strengthen understanding mechanisms of orphan inherited outer retinal degenerations and common AMD and Diabetic Retinopathy. It will also be greatly useful in building upon existing collaborations, and starting new ones that use the retina as a springboard into other Veteran-relevant disease states that are the focus of other outstanding VA Investigators. The Multimodal Retinal Imaging System Upgrade will also serve as a training tool for students and the next generation of investigators.