Core C: In-Vivo Imaging of Mucus Obstruction and Clearance Non-invasive imaging of the lung is an integral part of clinical projects 3 and 4 for the grant proposal ?Development of Novel Mucolytic Therapies for Lung Disease?. It is widely recognized that reduced lung function is associated with compromised clearance of mucus from the airways surface and mucus accumulation/plugging in the airways for both cystic fiibrosis and asthma. The ability to image the slowing of mucociliary and cough clearance by 2D gamma scintigraphy and the effects of mucus obstruction by magnetic resonance imaging (MRI) of fluorine 19 gas ventilation provides the clinical projects with powerful tools to assess the efficacy of new mucolytics. The goals of the in-vivo imaging core are to provide 1) measurements of mucociliary and cough clearance (MCC/CC) by gamma scintigraphy, 2) assessment of radio-particle deposition and clearance heterogeneity, 3) quantitative measures of pulmonary function on a regional basis, and 4) direct evaluation of lung ventilation through 19F MRI ventilation imaging. Baseline and post mucolytic treatment MCC/CC rates will be measured in CF and asthmatic patients by 2D gamma scintigraphy of inhaled/deposited radiolabeled (Tc99m) sulfur colloid particles on the bronchial airway surface. In the same patients 19F MRI will provide the ability to detect lobar changes in ventilation kinetics through a wash-in and wash-out phase of inhaled gas with high sensitivity. Demonstrating the potential of the 19F technique may contribute to its utility for evaluating airway diseases. In combination these two imaging modalities may provide new, sensitive regional measures of disease and heterogeneity of mucus accumulation that may be modified by novel mucolytics.
Muco-obstructive lung diseases, including asthma, CF, and COPD constitute major health burdens to citizens of the United States. This tPPG aims to develop new and effective therapies to help patients in need of treatment for these diseases. This core will evaluate the effectiveness of those therapies using novel lung imaging methods in patients with cystic fibrosis and asthma.
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