Comparing Chest Images From MRI to CT in Patients With Cystic Fibrosis (CF)

Cystic Fibrosis (CF), the most common inherited disease in Caucasians, is characterized by
chronic pulmonary inflammation and progressive loss of gas exchange units that eventually
results in respiratory failure. There is strong evidence that in CF abnormally low vascular
perfusion carries a high risk of death independent from the presence of pulmonary
hypertension. However, the evolution of pulmonary vascular disease in CF and how it might
contribute to the rate of decline in lung function is not known. Knowledge remains limited to
the results of old observational studies which concluded that the major causes of pulmonary
vascular remodeling and hypertension in CF are hypoxic respiratory failure and destruction of
lung tissue. Recent data obtained by state-of-the-art Magnetic Resonance Imaging (MRI) of the
pulmonary circulation, challenges the existing paradigm. Studies demonstrate that in the
absence of hypoxia, significant changes in pulmonary perfusion and in surrogate measures of
vascular resistance as well as in collateral blood flow begin early in the course of CF. The
newly developed therapeutics in the last decade which altered dramatically the course of
patients suffering from pulmonary vascular disease provide opportunities to understand the
role of pulmonary vasculature in CF lung disease.

This pilot study (Pilot 3) will assess the relationships between pulmonary perfusion, serum
markers of pulmonary inflammation and vascular remodeling, and hemodynamic measures
consistent with pulmonary hypertension. This study will establish MRI as a readily obtainable
modality to be used in the CF population to obtain measurements of pulmonary perfusion;
pulmonary arterial hemodynamic, dimension, and flow measures; and ventricular mass and
function measures.

The primary goal of this study is to improve the understanding of pulmonary vascular disease
in CF by examining pulmonary perfusion abnormalities and their association with markers of
pulmonary inflammation and pulmonary vascular remodeling, the severity of obstructive airways
disease, and pulmonary hemodynamic abnormalities in CF.

This study will include a single MRI of the pulmonary circulation on about 36 pediatric and
adult patients with CF and about 12 non-CF controls. UTE (Ultrashort Echo Time) MRI will be
performed without contrast. CF patients who are scheduled for clinical chest CT will be
enrolled and the scheduling of the MRI will be coordinated with the clinical CT. CF subjects
may also choose to enroll independent of clinical CT and choose to have a CT for research
purposes only. Other study procedures include blood specimen for serum biomarkers and lung
tests called spirometry and Lung Clearance Index (LCI) determined by Multiple Breath Washout
test. Blood specimens will be analyzed for a panel of inflammatory markers.

Inclusion Criteria:

- Age 5 and older

- Diagnosis of cystic fibrosis confirmed by a prior sweat chloride evaluation of > 60
mmol/liter or by two identified CF mutations on genetic analysis; or no CF for
controls

- Able to perform acceptable and repeatable spirometry per American Thoracic
Society/European Respiratory Society (ATS/ERS) joint consensus criteria.

- If CF, have valid spirometry data for at least 3 years

- If under the age of 18, the patient must assent to participation in the study, and the
patient's parent or guardian must be able to give written informed consent and comply
with the requirements of the study protocol

- If 18 years of age or older, the patient must be able to give written informed consent
and comply with the requirements of the study protocol

- Negative serum pregnancy test (for women of child bearing age)

- Able to tolerate MRI without sedation

Exclusion Criteria:

- Pregnancy (a negative serum pregnancy will be performed for all women of childbearing
potential within 7 days of imaging) or lactation

- Subjects with a history of renal

- Subjects with a history of hypersensitivity to gadolinium (Magnevist)

- Contraindications specific to MRI including a history of claustrophobia, cardiac
pacemaker, or other non-MRI compatible surgical implants (This includes
neuro-stimulators containing electrical circuitry, or which generate electrical
signals and/or have moving metal parts, and metal orthopedic pins or plates. The
research coordinator and/or the MRI technologist will screen all patients using the
standard checklist of medical history and safety questions used by the Radiology
Department in routine clinical scans.)

- Inability to comply with study procedures