HYPERPOLARIZED 3HE MRI OF THE MURINE HOUSE DUST MITE MODEL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 In Vivo 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.