ShEEP Request for Upgrade to Retinal Optical Coherence Tomography Instrumentation

ShEEP 请求升级视网膜光学相干断层扫描仪器

• 批准号: 9796783
• 负责人: JOHN M. SULLIVAN
• 金额: --
• 依托单位: VA WESTERN NEW YORK HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9796783
• 关键词: Address; Adult; Age related macular degeneration; Aging; American; Architecture; Area; Biological Models; Blood Vessels; Collaborations; Communicable Diseases; Coupled; Data Analyses; Development; Devices; Diabetic Retinopathy; Disease; Elderly; Elements; Endophthalmitis; Environment; Equipment; Eye; Fluorescein Angiography; Fluorescence; Flying body movement; Focal Infection; Fundus; Fundus photography; Grant; Growth; Health; Healthcare; Image; Imaging technology; Incentives; Inherited; Injury; Institution; Investigation; Klebsiella pneumonia bacterium; Laboratories; Lasers; Macular degeneration; Manufacturer Name; Measures; Metabolism; Microanatomy; Mission; Modality; Modeling; Multimodal Imaging; Mus; Mutation; Nerve Degeneration; Ophthalmoscopes; Optical Coherence Tomography; Optics; Orphan; Parkinson Disease; Pathogenicity; Photoreceptors; Program Evaluation; Property; Rattus; Request for Applications; Research; Research Personnel; Resolution; Retina; Retinal; Retinal Degeneration; Rodent; Scanning; Site; Spottings; Students; System; Systemic infection; Technology; Testing; Therapeutic; Therapeutic Studies; Thick; Time; Tissues; Toxic effect; Training; Trauma; United States National Institutes of Health; Veterans; Viral Vector; Visual; Work; adaptive optics; age related; base; body system; causal variant; cell type; cost; design; disability; disorder of macula of retina; fluorescence imaging; gene therapy; imaging platform; imaging system; innovation; instrument; instrumentation; interest; multidisciplinary; multimodality; next generation; novel; novel therapeutics; pre-clinical; retinal imaging; therapeutic gene; tool; vector

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.

此共享设备评估计划（ShEEP）应用程序要求对 现有的超高分辨率视网膜光学相干断层扫描（OCT）仪器 该仪器将大大提高现有视网膜变性研究的技术潜力， 允许开展现有文书难以或不可能实现的合作。 现有的仪器，虽然功能，是旧的技术，只能正面成像和b扫描 横截面成像，数据分析是繁琐和缓慢的，虽然最初对我们的竞争力很强， 研究小组在2011年，它不再激励研究回答的研究问题， 在当代临床前视网膜研究中至关重要。视网膜研究的挑战之一是 在相同的视网膜体积元素中的多个测量。这可以包括，例如， 评估特定细胞类型的活力的分段视网膜层厚度（例如，光感受器）， 同时评估成像视网膜的哪个区域被病毒载体转导，以确定 载体的治疗性货物是否成功地挽救了视网膜变性，或者， 促进毒性。此次升级将为标准的高分辨率OCT增加六种额外模式。 这些包括：1）眼底照相，2）眼底自体荧光，3）眼底荧光任意 荧光，4）血管造影，5）血管造影-OCT和6）自适应光学。所有的附加 这些模式将完全集成到现有的UHR OCT平台中，并使用 升级多个项目将大大有助于升级。沙利文实验室（创意冠军）将 直接受益于多模态OCT机器，解决临床前基因治疗中的关键变量 研究（VA和NIH支持），例如，其中可以定量外部视网膜治疗拯救。 与确定性测量的视网膜外细胞病毒载体转导区域相关。Fliesler实验室将 直接受益于多模式OCT机器，可以评估外部视网膜变性以及血管 可能发生在眼爆炸伤中的伤害。冯氏实验室将受益于获得增强的仪器 这可以阐明与帕金森病因果相关的特定基因突变对帕金森病的影响。 啮齿动物视网膜的显微解剖和功能，并与沙利文实验室合作开发和测试基因 视网膜中PD的治疗剂。Russo实验室对眼睛感兴趣， 建立全身性感染，由于高毒力克雷伯菌肺炎而在眼内形成病灶 以及辨别致病性变量并采取措施以获得新的治疗策略。特伦实验室是 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的人提供了 与沙利文实验室合作的机会，以研究疾病的机制和发展 新的治疗方法。总之，升级多模式视网膜成像系统将在以下方面非常有用： 加强临床前基因治疗策略的技术方法，加强理解 孤儿遗传性外视网膜变性和常见的AMD和糖尿病视网膜病变的机制。它将 在现有的合作基础上建立，并开始使用视网膜作为一个新的合作， 跳板进入其他退伍军人相关的疾病状态，是其他杰出的VA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个培训工具， 一代调查员。