ShEEP Request for In Vivo Imaging System

ShEEP 请求体内成像系统

• 批准号: 9903620
• 负责人: THOMAS J HORNYAK
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903620
• 关键词: 3-Dimensional; Acute; Acute Brain Injuries; Acute Lung Injury; Anatomy; Anesthesia procedures; Animal Model; Animals; Area; Autopsy; Baltimore; Binding; Bioluminescence; Brain; Brain Ischemia; Breast Cancer Cell; Cell physiology; Cells; Colonic Neoplasms; Computers; Core Facility; Deep Vein Thrombosis; Doctor of Medicine; Doctor of Philosophy; Dose; Elevator; Encephalitis; Endotoxins; Fluorescence; Fluorochrome; Funding; Gases; Glial Fibrillary Acidic Protein; Gliosis; Health; Healthcare Systems; Image; Imaging Device; Immune; Individual; Infiltration; Inflammation; Inflammatory; Ischemia; Label; Laboratories; Lesion; Light; Longitudinal Studies; Luciferases; Lung; Lung diseases; MAPK14 gene; Maryland; Matrilysin; Measurement; Measures; Medical; Medical center; Metastatic to; Microfluidic Microchips; Minor; Modality; Molecular; Mus; Neoplasm Metastasis; Optics; Organ; Patients; Peripheral; Permeability; Pharmaceutical Preparations; Phenotype; Price; Principal Investigator; Process; Pulmonary Fibrosis; Rattus; Regenerative Medicine; Reperfusion Injury; Reperfusion Therapy; Reporter; Research; Research Personnel; Research Project Grants; Resolution; Rodent; Sales; Scanning; Services; Sheep; Stem cells; System; Testing; Thrombus; Time; Training; Transgenic Mice; Transillumination; Transplantation; Tumor Burden; Veterans; Work; X-Ray Computed Tomography; Xenograft procedure; anatomic imaging; animal imaging; anticancer research; base; clinically relevant; colon cancer metastasis; colon cancer progression; complex biological systems; discount; experimental study; flexibility; fluorescence imaging; imaging software; imaging study; imaging system; in vivo; in vivo imaging; in vivo imaging system; inhibiting antibody; insight; instrument; melanocyte; microCT; migration; mouse model; non-invasive imaging; novel; novel therapeutics; operation; optical imaging; price lists; regenerative; research and development; research study; response; screening; small molecule; tomography; tumor progression; user-friendly; whole animal imaging

The project is a ShEEP request for a Perkin-Elmer IVIS SpectrumCT in vivo Imaging System, which will bring a new capability for performing whole animal imaging studies to the research core laboratories at the Baltimore VA Medical Center. The IVIS SpectrumCT in vivo Imaging System has integrated 2D and 3D optical imaging and microCT modalities; which allow simultaneous molecular and anatomical longitudinal studies, providing researchers with essential insights into complex biological systems in small animal models. The instrument will facilitate individual VA investigators with widely varying projects to perform a variety of whole animal imaging studies. The requested instrument will support the work of the entire Baltimore VA Medical Center Research Service, including six major VA Merit funded users (Drs. Hornyak, Antalis, Hasday, Hu Martin, and Xie, and one minor user (Dr. Raufman). Thomas J. Hornyak, M.D., Ph.D., Associate Chief of Staff (ACOS) for Research and Development (R&D) at the VA Medical Health Center System (VAMHCS) is the Principal Investigator (PI) for this proposal. He is also PI on the Merit Review project,“Melanocyte Stem Cells in Regenerative Medicine”. He and his laboratory will use the IVIS Spectrum CT to track in vivo the survival, localization, and migration of labeled stem cells introduced for regenerative purposes. Thereby, maximizing the amount of information obtained with each individual experiment and thus contributing to more rapid progress. Toni Antalis, Ph.D. is a VA funded investigator whose research seeks to better understand the molecular and cellular processes that regulate thrombus resolution, so that specific therapies to accelerate the resolution process can be developed. Her group will use fluorescent reporter markers to perform 2D and 3D in vivo imaging of animals for this study, allowing for molecular and anatomical non-invasive imaging in mouse models of deep vein thrombosis. Jeffrey Hasday, MD., is a VA Merit funded investigator whose VA Merit project focuses on screening existing small molecules selected to bind to a pocket within the substrate binding groove of p38alpha as a novel therapeutic for acute lung disease. His experimental plan includes testing in a mouse model of acute lung injury induced by intratracheal instillation of endotoxin. The IVIS SpectrumCT system will allow his laboratory to follow mice with sequential measurements of lung permeability using the near-IR probe Angiosense 680 EX. Bingren Hu’s VA Merit research studies novel mechanisms underlying brain ischemia- reperfusion (IR) injury. His laboratory will utilize the IVIS SpectrumCT to study gliosis using glial fibrillary acidic protein (GFAP) luciferase transgenic mice, and brain inflammation using CX3CR1-GFP mice after brain ischemia. They will also use it to study migration and infiltration of inflammatory and immune cells from peripheral organs to the brain in a mouse model of brain ischemia and reperfusion. Stuart Martin, Ph.D.’s funded VA research project uses a novel microfluidic device to rapidly image free-floating breast tumor cells and define phenotypes that are predictive of metastatic potential. These phenotypes are then related to metastatic potential and drug response using clinically-relevant patient-derived xenograft transplants in mice. The requested instrument will be used to quantitatively measure metastatic tumor burden to specific organs in these mice. MDs Guofeng Xie and Jean-Pierre Raufman’s individual work focus on molecular mechanisms behind colon cancer progression. Dr. Xie will use the IVIS SpectrumCT to quantitatively measure tumor progression in live animals using the mouse model of colon cancer metastasis, and to determine if anti-matrix metallo-proteinase 7 (MMP7) antibodies inhibit colon cancer progression. Dr. Raufman will use the requested system for in vivo luciferase bioluminescence luciferase imaging of colon tumor formation and metastasis in his animal model. Using the requested imaging system for longitudinal studies, he can avoid euthanizing mice before a meaningful number of metastases develop. He will also be able to detect lesions too small or deep to be seen by gross post-mortem sectioning – enhancing his ability to measure a critical endpoint.

该项目是针对Perkin-Elmer IVIS SpectrumCT体内成像系统的ShEEP申请，该系统将 为研究核心实验室带来了进行整体动物成像研究的新能力， 巴尔的摩退伍军人医疗中心。IVIS SpectrumCT体内成像系统集成了2D和3D光学 成像和microCT模式;允许同时进行分子和解剖纵向研究， 为研究人员提供了在小动物模型中对复杂生物系统的重要见解。 该工具将有助于各个VA调查人员进行各种各样的项目， 整个动物成像研究。所要求的仪器将支持整个巴尔的摩弗吉尼亚州的工作 医学中心研究服务，包括六个主要的VA Merit资助的用户（Hornyak博士，Antalis博士，Hasday博士， Hu Martin和Xie以及一名未成年用户（Raufman博士）。托马斯J. Hornyak，医学博士，哲学博士、副主任 VA医疗健康中心系统（VAMHCS）的研究与开发（R&D）工作人员（ACOS）是 主要研究者（PI）。他还是Merit Review项目的PI，“黑素细胞干细胞在 再生医学”。他和他的实验室将使用IVIS Spectrum CT来跟踪体内存活情况， 定位和迁移的标记干细胞引入再生的目的。因此， 通过每个单独的实验获得的信息量，从而有助于更快的进展。 Toni Antalis博士是VA资助的研究人员，其研究旨在更好地了解分子和 调节血栓消退的细胞过程，因此， 过程可以发展。她的团队将使用荧光报告标记在体内进行2D和3D 用于本研究的动物成像，允许在小鼠模型中进行分子和解剖学非侵入性成像 深静脉血栓形成Jeffrey Hasday，医学博士，是一名退伍军人管理局优秀奖资助的研究员， 重点是筛选现有的小分子选择结合到口袋内的基板结合槽 p38 α作为急性肺病的新疗法。他的实验计划包括在老鼠身上进行测试 内毒素肺内灌注致急性肺损伤模型。IVIS SpectrumCT系统将 让他的实验室用近红外探针连续测量小鼠的肺渗透性 Angiosense 680 EX. Bingren Hu的VA Merit研究研究了脑缺血的新机制- 再灌注损伤。他的实验室将利用IVIS SpectrumCT研究神经胶质增生， 蛋白质（GFAP）荧光素酶转基因小鼠，以及使用CX 3CR 1-GFP小鼠的脑炎症， 缺血他们还将用它来研究炎症和免疫细胞的迁移和浸润， 在脑缺血和再灌注的小鼠模型中将外周器官移植到脑。斯图尔特·马丁博士S 一个由VA资助的研究项目使用一种新型的微流体装置来快速成像自由漂浮的乳腺肿瘤细胞 并确定预测转移潜能的表型。这些表型与 在小鼠中使用临床相关的患者来源的异种移植物移植物的转移潜力和药物反应。 所要求的仪器将用于定量测量特定器官的转移性肿瘤负荷， 这些老鼠谢国锋博士和让-皮埃尔·劳夫曼博士的个人工作主要集中在分子机制方面 结肠癌进展的背后谢医生将使用IVIS SpectrumCT定量测量肿瘤 使用结肠癌转移的小鼠模型在活体动物中的进展，并确定抗基质 金属蛋白酶7（MMP 7）抗体抑制结肠癌进展。Raufman医生将使用 用于HIS中结肠肿瘤形成和转移体内荧光素酶生物发光荧光素酶成像的系统 动物模型使用所要求的成像系统进行纵向研究，他可以避免对老鼠实施安乐死 才能出现有意义的转移他还将能够检测到太小或太深的病变， 通过大体尸检切片可以看到-增强了他测量关键终点的能力。