The long-term goal of this proposal is to establish a non-invasive MRI technique to measure and monitor airway secretions in patients with Cystic Fibrosis (CF). Cystic Fibrosis (CF) is an inherited disease associated with a severely impaired mucociliary clearance that leads to chronic polymicrobial airway biofilm infection, inflammation, airway remodeling and eventually respiratory failure in almost 80% of patients. Therapy includes airway clearance treatments, anti-inflammatory therapy along with inhaled antibiotics, hypertonic saline and rhDNase. Patients are followed clinically, radiographically, with lung function studies, and microbial cultures. Currently, imaging assessment of airways in patients with CF largely relies on static images from CT, which are helpful in assessing response to therapy but are severely limited because of the need for repeated measures and limitations of ionizing radiation dose. Even though structural MRI has been explored as a surrogate for CT, both CT and MRI are semi-quantitative and only evaluate the static nature of the lung. Clinical therapy and translational investigations have a critical need for a quantitative measure of excess lung secretions that could be used repeatedly. This grant is motivated by our recent observations of lung water density in CF patients utilizing a fast gradient echo (fGRE) magnetic resonance imaging (MRI) sequence that has been developed at UCSD for use with physiological studies. This noninvasive imaging sequence is capable of obtaining lung water density within a 9-sec breathhold and has been shown to be highly reliable for obtaining measuring lung density in healthy human subjects. Lung water density in healthy human subjects is a measure of water from blood and lung tissue but in CF subjects, lung water density includes water from excess airway secretions. Quantitative measures of lung water density obtained in 16 CF subjects with mild to severe lung disease have shown there are locations of abnormally high lung water density and these locations shift spatially after patients complete 2 to 4 vital capacity maneuvers. Neither observation is seen in healthy subjects. We suspect that these hyper-dense regions indicate the presence of excess secretions. Our broad hypothesis is that these hyper-dense regions will impact local ventilation and possible blood flow as measured by quantitative MRI techniques. Our rationale is that excess airway secretions in subjects with CF will produce a heterogeneous pattern of blood flow and ventilation and this pattern will change as local airways open and close as biofilm moves. This project has a potentially high reward since successful completion of these aims will provide an essential first assessment of the nature and physiologic significance of the observed high density regions. In summary, we believe the quantitative density MRI method described may fill a critical need for an objective measure of CF airway secretions that can be used repeatedly to assess disease severity and response to therapy.

Public Health Relevance

The goal of this proposal is to establish a non-invasive MRI technique to measure and monitor lung secretions in patients with Cystic Fibrosis and validate these measures with cutting-edge MRI to assess the physiologic impact on blood flow and ventilation in the presence of excess airway secretions.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Medical Imaging Study Section (MEDI)
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Liu, Guoying
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University of California San Diego
Schools of Medicine
La Jolla
United States
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