Obstructive Lung Diseases

Cystic Fibrosis

Cystic fibrosis (CF) is a lifelong disease that affects the respiratory, endocrine, reproductive, and digestive systems. About 30,000 children and adults in the United States (70,000 worldwide) have CF. This disease is caused by a defective gene that makes the body produce very thick, sticky mucus.

The cystic fibrosis transmembrane conductance regulator (CFTR) protein helps to maintain the balance of salt and water on many surfaces in the body, such as the surface of the lung. When the protein is not working correctly, chloride (a component of salt) becomes trapped in cells. Without the proper movement of chloride, water cannot hydrate the cellular surface. This leads the mucus covering the cells to become thick and sticky, causing many of the symptoms associated with cystic fibrosis.

We hypothesize that MRI will serve as a sensitive tool to longitudinally monitor CF lung disease progression and response to CFTR modulator therapy in children with CF, without exposure to ionizing radiation. We use advances in MRI technology to longitudinally evaluate CF lung disease via MRI, assessing disease progression and therapeutic efficacy in young CF patients precisely when CFTR modulators enter the clinic.

We do this with the following aims:

• To detect, quantify, and validate regional lung disease by UTE MRI through comparison with CT and pulmonary function tests in pediatric CF patients.
• To use UTE MRI to longitudinally quantify differences in disease trajectory between CF children undergoing CFTR modulator therapy and CF children with two CFTR mutations who are ineligible for therapy or are not treated with a CFTR modulator.
• To examine relationships between cross-sectional and longitudinal changes in UTE MRI and compare with sensitive tools that monitor CF ventilation, including hyperpolarized 129Xe ventilation MRI and lung clearance index (LCI).

Asthma

Asthma is a chronic condition involving the airways. All asthmatics experience variable, but widespread narrowing of the airways or bronchial tubes. The narrowing results from swelling of the airway lining, increased mucus production, tightening of the muscles around the airways and accumulation of inflammatory cells in the airway. This narrowing causes cough, wheeze, and shortness of breath.

We hypothesize that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. Our studies have measured regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma advancing our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has never been investigated in a pediatric asthma cohort.

Bronchopulmonary Dysplasia

Many babies born prematurely, especially those more than two months early, develop bronchopulmonary dysplasia (BPD), a chronic lung disease commonly seen in newborns. BPD includes lung disease, airway obstruction and pulmonary hypertension, in addition to other related conditions.

We have developed unique neonatal MRI capabilities that provide high-resolution, detailed images of lung parenchymal and vascular structures, regional cardiopulmonary function, and dynamic airway collapse, all during quiet breathing and without sedation or ionizing radiation. This collective information allows phenotyping of respiratory disease related to premature birth (bronchopulmonary dysplasia, BPD) and has the potential to significantly change the understanding and time course of this disease.

Chronic Obstructive Pulmonary Disease (COPD)

Many knowledge gaps in the nature of early chronic obstructive pulmonary disease (COPD) still exist, mainly because COPD has always been considered a disease of the elderly. Little attention has been paid to the pathologic changes in the lungs of young adults with risk factors for COPD, such as bronchopulmonary dysplasia. One major limitation is the current lack of noninvasive ways to sensitively measure or image functional declines from subjects who are at risk for COPD but haven't yet developed more significant clinical symptoms of the disease.

With the use of lung magnetic resonance imaging with hyperpolarized gas in the diagnostic workup for bronchopulmonary dysplasia with underlying chronic airflow limitation in presence of spirometry criteria that meet the diagnosis of early-onset COPD.