HYPERPOLARIZED 3HE MRI OF THE MURINE HOUSE DUST MITE MODEL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目的总体目标是在杜克建立过敏性哮喘的屋尘螨（HDM）小鼠模型，并对这些动物进行标准和HP 3 He MRI评价。第一阶段是建立屋尘螨致敏性肺部炎症模型。根据Merck的预期方案，在杜克的Mike Foster博士的实验室中用屋尘螨（HDM）对小鼠进行攻毒。在PBS或HDM给药后，通过BAL（评价支气管肺泡灌洗液中的总细胞计数和差异细胞计数）和肺功能测量（使用flexivent进行乙酰甲胆碱激发后）对小鼠进行表型分析。 一旦模型在杜克大学成功运行，将在乙酰甲胆碱（MCh）激发期间和之后对小鼠进行成像。小鼠将分为两组HDM和PBS处理的小鼠。每组将扫描四只小鼠。将在杜克的Mike Foster博士实验室根据Merck的预期方案对小鼠进行攻毒。将使用杜克在之前的默克合作中建立的方案在CIVM（体内显微镜中心）对它们进行扫描。将在颈静脉注射乙酰甲胆碱前后进行扫描。图像参数将在与默克科学家协商后选择，但将基于我们最近开发的协议，包括基线（预 MCh）3D扫描，分辨率为156 <$156 <$1000 <$m3，随后是2D时间序列，包括每12秒拍摄的186 <$186 <$m2的10张图像。在第一个2D图像后，将给予小鼠MCh激发并记录时间反应。在2D系列之后，将立即收集与基线具有相同分辨率的另一个3D图像，以捕获持续缺陷。 成像后，小鼠将接受BAL液的收集或保存其左肺，并冷冻返回Merck Frosst。这将作为替代终点，以检查HDM挑战是否有效并给出正确的表型。 根据第一阶段研究的结果，默克准备赞助进一步的研究，以评估该模型中不同的药物反应。

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.