Cystic fibrosis (CF) results in the thickening of mucus in the lungs and other organs due to dysfunction of a transmembrane conductance protein. This allows buildup of bacteria that results in inflammation, leading to tissue breakdown and loss of function. In the lungs, this process causes loss of air exchange structures progressing to diminished lung function. The exchange of oxygen in the lungs depends on both the integrity of air conduits and vasculature. Most clinical assessments, however, focus on ventilatory function, with the assumption that any vascular compromise is secondary. Nevertheless, there is evidence, some from the investigator's lab, to suggest that perfusion anomalies in the lung occur before signs of ventilatory dysfunction. Thus, the inflammatory processes of CF may impact pulmonary microvasculature specifically and concurrently or prior to damage to ventilatory structures. This study aims to apply a new MRI method to serially measure regional lung perfusion, without the use of contrast agent, in children with CF and to associate it with regional assessments of ventilation and to serum cytokines or proteomic markers of angiogenesis and inflammatory processes.

The investigator's lab has recently developed a noninvasive, non-contrast, method of labeling blood flowing into the lungs and generating a map of perfusion. The investigator aims to couple this technique to existing methods using hyperpolarized Xenon to map ventilation. The investigator will apply these methods over time in CF patients, monitoring the relationship between regional perfusion and ventilation defects.

This pilot work will provide the foundation for larger studies to establish the essential etiological role of perfusion deficits in CF.

The Lung Perfusion in CF trial is a case-control observational study conducted at Cincinnati Children's Hospital.

Patients will be assessed before and approximately 6 months after the clinical initiation of triple-combination modulator therapy with the following imaging to demonstrate aim 1, that pulmonary perfusion is regionally altered in CF patients in association with the status and progression of lung ventilatory function: Ultra-short echo time (UTE) protocol to obtain structural lung imaging primarily for anatomic reference, Hyperpolarized Xenon gas inhalation protocol to measure regional lung ventilation and arterial spin labeling protocol to measure regional lung perfusion.

To demonstrate aim 2, that different profiles of serum proteomic markers related to angiogenesis and vascular remodeling, characterize states of pulmonary hyperfusion and hypoperfusion, blood sample data analysis from a separate study conducted at Cincinnati Children's Hospital Medical Center will also be obtained before and 6 months after initiation of triple-combination modulator therapy.

Safety will be assessed by recording adverse events. Vital signs (heart rate, SPO2) will be recorded before, immediately following inhalation, and 2 minutes after each Xenon gas inhalation; O2 saturation will be monitored continuously throughout the Xenon portion of the MRI, and the time and duration of nadir will be recorded.

The overarching goal of this study is to demonstrate that arterial spin labeling MRI lung perfusion can be used to measure regional manifestations of pulmonary vascular disease in CF that precedes and contributes to global and local decline in ventilatory lung function.

Inclusion Criteria:

Inclusion CF Cohort

• male or female between the ages of 6 through 21 years

• diagnosis of CF by positive sweat test and genetic test

• planning to start Trikafta based on clinical decision

• baseline pulmonary function test (PFT) defined as FEV1% that is no less than 5% of the best PFT in the previous 6 months

• Absence of exacerbation defined as

  • No acute antibiotic usage for 14 days prior to MRI visit
  • Able to perform an acceptable and reproducible spirometry
  • O2 saturation level at 90% or greater when laying flat

Inclusion Healthy Control Cohort

• male or female between the ages of 6 through 21 years
• no known diagnoses that impact lung function in the opinion of the investigators

Exclusion Criteria:

Exclusion both cohorts

• standard MRI exclusions (metal implants, claustrophobia)
• pregnancy