ShEEP Request for In Vivo Imaging System

该项目是对Perkin-Elmer IVIS SpectrumCT in vivo成像系统的绵羊请求，该系统将 将进行整体动物成像研究的新能力带到位于 巴尔的摩退伍军人医疗中心。IVIS SpectrumCT活体成像系统集成了2D和3D光学 成像和显微CT模式；允许同时进行分子和解剖学纵向研究， 为研究人员提供了对小动物模型中复杂生物系统的基本见解。 该工具将促进退伍军人管理局调查人员与广泛不同的项目进行各种 完整的动物成像研究。所要求的文书将支持整个巴尔的摩退伍军人管理局的工作。 医疗中心研究服务，包括退伍军人事务部资助的六个主要用户(Hornyak，Antalis，Hasday， Hu Martin和Xie，以及一个小用户(Raufman博士)。Thomas J.Hornyak，医学博士，副首席执行官 退伍军人医疗保健中心系统(VAMHCS)负责研发(R&D)的工作人员(ACO)是 这项建议的首席调查员(PI)。他也是功绩评估项目的私家侦探， 再生医学“。他和他的实验室将使用IVIS Spectrum CT在体内跟踪存活情况， 为再生目的引入的标记干细胞的定位和迁移。因此，最大化 从每个单独的实验中获得的信息量，从而有助于更快的进展。 托尼·安塔利斯博士是退伍军人管理局资助的一名研究员，他的研究旨在更好地理解分子和 调节血栓溶解的细胞过程，因此特定的治疗方法可以加速溶解 可以开发工艺。她的团队将使用荧光报告标记在体内进行2D和3D 这项研究的动物成像，允许在小鼠模型中进行分子和解剖学的非侵入性成像 深静脉血栓形成的可能性。杰弗里·哈斯迪，医学博士，是一名退伍军人功勋资助的研究员，他的退伍军人功勋项目 重点是筛选被选择结合到底物结合槽内的口袋中的现有小分子 P38α作为治疗急性肺部疾病的新疗法。他的实验计划包括在老鼠身上进行试验。 气管内滴注内毒素致急性肺损伤模型的建立。IVIS SpectrumCT系统将 允许他的实验室使用近红外探头连续测量小鼠的肺通透性 Angiosense 680 ex.胡炳仁的VA优点研究研究脑缺血的新机制- 再灌流(IR)损伤。他的实验室将利用IVIS SpectrumCT研究使用胶质纤维酸性蛋白的胶质细胞增生症 蛋白(GFAP)荧光素酶转基因小鼠及CX3CR1-GFP小鼠脑后炎症 缺血症。他们还将用它来研究炎症和免疫细胞的迁移和渗透。 外周器官到脑的小鼠脑缺血再灌流模型。斯图尔特·马丁，S博士 由VA资助的研究项目使用一种新型微流控设备来快速成像自由漂浮的乳腺肿瘤细胞 并定义可预测转移潜能的表型。然后，这些表型与 临床相关患者来源的小鼠异种移植的转移潜能和药物反应。 所要求的仪器将用于定量测量转移性肿瘤对特定器官的负担 这些老鼠。MDS谢国锋和让-皮埃尔·劳夫曼的个人工作集中在分子机制上 结肠癌进展的背后。谢博士将使用IVIS SpectrumCT来定量测量肿瘤 利用小鼠结肠癌转移模型研究活体动物的进展，并确定是否有抗基质 金属蛋白酶7(MMP7)抗体可抑制结肠癌的进展。Raufman博士将使用请求的 HIS结肠癌形成和转移的荧光素酶生物发光酶体内成像系统 动物模型。使用所要求的成像系统进行纵向研究，他可以避免安乐死小鼠 在有相当数量的转移之前。他还将能够检测到太小或太深的损伤 通过尸检可以看到--增强了他测量关键终点的能力。

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.