HYPERPOLARIZED 3HE MRI OF THE MURINE HOUSE DUST MITE MODEL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的总体目标是在杜克大学建立家尘螨(HDM)小鼠哮喘模型，并对这些动物进行标准的和HP3He磁共振成像评估。第一阶段将建立过敏性肺部炎症的屋尘螨模型。根据默克公司期望的方案，这些小鼠将在杜克大学迈克·福斯特博士的实验室里接受室内尘螨(HDM)的挑战。在给予PBS或HDM后，小鼠将通过BAL(评估支气管肺泡灌洗中的细胞总数和分类计数)和肺功能测量(在使用FLEVIVENT的乙酰甲胆碱激发后)进行表型鉴定。 一旦该模型在杜克大学成功运行，将在乙酰甲胆碱(MCH)挑战期间和之后对小鼠进行成像。这些小鼠将被分成HDM和PBS处理的两组小鼠。每组四只老鼠将被扫描。这些小鼠将在杜克大学迈克·福斯特博士的实验室里按照默克公司期望的方案接受挑战。他们将在CIVM(体内显微镜中心)使用杜克在之前与默克公司的合作中建立的协议进行扫描。在颈静脉注射乙酰甲胆碱前后进行扫描。图像参数的选择将与默克公司的科学家协商，但将基于我们最近开发的协议，该协议包括基线(前 MCH)以156？156？1000？m~3的分辨率进行三维扫描，然后是每12秒拍摄186？186？m~2的10个图像的2D时间序列。在第一个2D图像之后，鼠标将被给予MCH挑战并记录时间反应。在2D系列之后，将立即收集另一幅分辨率与基线相同的3D图像，以捕捉永久性缺陷。 成像后，小鼠将接受BAL液的收集或保存，它们的左肺将被保存并冷冻，以便返回默克·弗罗斯特。这将用作代理终结点，以检查HDM质询是否有效并提供正确的表型。 根据这项研究第一阶段的结果，默克公司准备赞助进一步的研究，以评估该模型中的不同药物反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this project is to establish the House Dust Mite (HDM) Murine model of alleric asthma at Duke, and to conduct standard and HP 3He MRI evaluation of these animals. The first phase will be to establish the house dust-mite model of allergic lung inflammation. The mice will be challenged with House Dust Mite (HDM) according the Merck's desired protocol in the laboratory of Dr. Mike Foster at Duke. Mice will be phenotyped after either PBS or HDM administration by BAL (evaluating total and differential cell counts in bronchoalveolar lavage) and lung function measurements (after methacholine challenge using the flexivent). Once the model is successfully running at Duke University, mice will be imaged during and after Methacholine (MCh) challenge. The mice will be in two groups of HDM and PBS treated mice. Four mice will be scanned in each group. The mice will be challenged according the Merck's desired protocol in the laboratory of Dr. Mike Foster at Duke. They will be scanned at CIVM (Center for InVivo Microscopy) using the protocol that has been established by Duke in previous Merck collaborations. A scan before and after jugular methacholine delivery will be made. The image parameters will be chosen in consultation with Merck scientists, but will be based on our recently developed protocol consisting of a baseline (pre- MCh) 3D scan with resolution of 156¿156¿1000¿m3 followed by a 2D temporal series consisting of 10 images at 186¿186¿m2 taken every 12 sec. After the first 2D image, the mouse will be given a MCh challenge and the temporal response recorded. Immediately following the 2D series, another 3D image with the same resolution as the baseline will be collected to capture the persistent defects. After imaging mice will undergo collection of BAL fluid or save their left lung will be saved and frozen for return to Merck Frosst. This will serve as a surrogate endpoint to check that the HDM challenge worked and gave the correct phenotype. Based on the outcome of this first phase of the study, Merck is prepared to sponsor further studies to evaluate different drug responses in this model.