19F MRI in Healthy Children and Children With Mild Cystic Fibrosis Lung Disease

A Cross-sectional Pilot Study of 19F MRI in Healthy Children and Children With Mild Cystic Fibrosis Lung Disease

This study capitalizes on the emerging technology of 19F MRI, using conventional 'thermally' polarized perfluorinated gas (perfluoropropane, or PFP) mixed with oxygen and studied with magnetic resonance imaging (MRI) to visualize ventilation. This technique has not been studied in children.

Children and adolescents (6-17 years old) with cystic fibrosis (CF) who have normal spirometry will undergo 19F MRI with the inhalation of an inert contrast gas to study ventilation. Comparisons will be made to a cohort of healthy children (6-17 years old) who will perform the same measures. The primary outcome measure is the feasibility of conducting these studies in the pediatric population. Parallel performance of multiple breath nitrogen washout (MBW) and spirometry will be used to compare the sensitivity of these outcomes to the presence of mild lung disease in these children. Finally, the investigators will compare data obtained during standard breath holds with a novel "free-breathing" technique that will eliminate the need for breath holds during MRI acquisition.

Study Overview

• Status: Not yet recruiting
• Conditions: Cystic Fibrosis in Children
• Intervention / Treatment: Combination product: 19F MRI

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

• Study Contact: Name: Jennifer L Goralski, MD; Phone Number: 919-445-0331; Email: jennifer_goralski@med.unc.edu
• Study Contact Backup: Name: Margret Z Powell, BS; Phone Number: 984-974-2962; Email: margret_powell@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Univeristy of North Carolina at Chapel Hill
      • Contact: Jennifer L Goralski, MD; Phone Number: 919-445-0331; Email: jennifer_goralski@med.unc.edu
      • Principal Investigator: Jennifer L Goralski, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers between the ages of 6-17 years old without known lung disease OR people with cystic fibrosis between the ages of 6-17 years

Description

Inclusion Criteria:

• 6-17 years old
• Non-smoker and non-vaper
• Cystic Fibrosis (CF) Group: must have a diagnosis of CF
• No use of supplemental oxygen
• They must be able to perform spirometry and have stable lung function (within 10% personal best in the last 6 months) and no exacerbations within the past 4 weeks
• Baseline forced expiratory volume in 1 second (FEV1) >80% with ratio of the forced expiratory volume in the first one second to the forced vital capacity of the lung (FEV1:FVC) ratio >0.7

Exclusion Criteria:

• Healthy volunteers: with any history of chronic lung disease (i.e. asthma)
• Active or former smoker with less than 1 year of quitting

• Unable to undergo an MRI of the lungs and chest because of contraindications, including:

  • Injury to the eye involving a metallic object
  • Injury to the body involving a metallic object
  • Presence of an implanted drug infusion device that is not MRI safe
  • Bone growth of fusion simulator
  • Presence of cochlear, otologic, or ear implant
  • Shunt (spinal or intraventricular)
  • Any implant held in place by magnet
  • Claustrophobia
• Unable to tolerate the inhalation of the gas mixture
• Facial hair preventing a tight fit of the mask used in the study
• Pregnancy
• Changes in medication that may affect CF lung disease or lung function in the past 28 days, including experimental therapies

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children with CF; All subjects to receive inhaled perfluoropropane during MRI procedures, including standard breath hold and free-breathing technique. Subjects will breathe the gas for 5 breath hold cycles (variable volumes as lung capacity/size varies per participant).	Combination product: 19F MRI; Inhalation of a biologically inert contrast gas, perfluoropropane, combined with 19F-tuned MRI with image acquisition at breath-hold and during tidal breathing.; Other Names: PFP
Healthy Children; All subjects to receive inhaled perfluoropropane during MRI procedures, including standard breath hold and free-breathing technique. Subjects will breathe the gas for 5 breath hold cycles (variable volumes as lung capacity/size varies per participant).	Combination product: 19F MRI; Inhalation of a biologically inert contrast gas, perfluoropropane, combined with 19F-tuned MRI with image acquisition at breath-hold and during tidal breathing.; Other Names: PFP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participation rate	The number of eligible participants approached for the study divided by the number who consent to participate.	through study completion, recruitment for 2 years
Completion rate	The number of consented participants divided by the number of participants who complete each portion of the study.	through study completion, recruitment for 2 years
Parental acceptability score	Acceptability questionnaire for guardian; 2 questions, each on a 10 point Likert scale; Implementation: qualitative description of barriers encountered; Practicality: % of participants completing the study with research quality data	Day 1, assessed at single visit
Child acceptability score	Acceptability questionnaire for participant; 2 questions, each on a 10 point Likert scale; Implementation: qualitative description of barriers encountered; Practicality: % of participants completing the study with research quality data	Day 1, assessed at single visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI defined ventilation defect parameters (VDP) in healthy participants	The 19F Volumetric interpolated breath-hold examination (VIBE) scans and proton nuclear magnetic resonance imaging (1H-MRI) will be saved as Digital Imaging and Communications in Medicine (DICOM) images and imported to Medical Image Merge (MIM) software. The percentage of lung with ventilation defects (VDP) after the 5th inspiratory cycle will be measured, using the 95th percentile of background noise on the last wash-in scan as the threshold value defining absence of ventilation. The investigators will assess ventilation defect parameters (VDP) scored in healthy participants (mean + SD)	Day 1, assessed at single visit
MRI defined fraction of lung volume with slow gas washout time (FLVlongtau2) in healthy participants	The 19F Volumetric interpolated breath-hold examination (VIBE) scans and 1H-MRI will be saved as Digital Imaging and Communications in Medicine (DICOM) images and imported to Medical Image Merge (MIM) software. The fraction of the total lung volume with slow gas wash-out kinetics (FLV↑tau2) will be calculated for lung regions without an overlapping full ventilation defect. The investigators will assess FLVlongtau2 scored in healthy participants (mean + SD)	Day 1, assessed at single visit
MRI defined VDP in participants with cystic fibrosis	The 19F VIBE scans and 1H-MRI will be saved as Digital Imaging and Communications in Medicine (DICOM) images and imported to Medical Image Merge (MIM) software. The percentage of lung with ventilation defects (VDP) after the 5th inspiratory cycle will be measured, using the 95th percentile of background noise on the last wash-in scan as the threshold value defining absence of ventilation. The investigators will assess ventilation defect parameters (VDP) scored in participants with cystic fibrosis (mean + SD)	Day 1, assessed at single visit
MRI defined fraction of lung volume with slow gas washout time (FLVlongtau2) in participants with cystic fibrosis	The 19F Volumetric interpolated breath-hold examination (VIBE) scans and 1H-MRI will be saved as Digital Imaging and Communications in Medicine (DICOM) images and imported to Medical Image Merge (MIM) software. The fraction of the total lung volume with slow gas wash-out kinetics (FLV↑tau2) will be calculated for lung regions without an overlapping full ventilation defect. The investigators will assess FLVlongtau2 scored in participants with cystic fibrosis (mean + SD)	Day 1, assessed at single visit

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Jennifer L Goralski, MD, UNC Chapel Hill

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: September 20, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: pediatrics; ventilation; 19F MRI
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Lung Diseases, Interstitial; Fibrosis; Lung Diseases; Pulmonary Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 23-0700; 5K23HL138257-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No