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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cystic Fibrosis in Children

Intervention / Treatment
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* Combination Product: 19F MRI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children with CF<br>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<br>* Inhalation of a biologically inert contrast gas, perfluoropropane, combined with 19F-tuned MRI with image acquisition at breath-hold and during tidal breathing.<br>* Other names: PFP;|
| Healthy Children<br>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<br>* Inhalation of a biologically inert contrast gas, perfluoropropane, combined with 19F-tuned MRI with image acquisition at breath-hold and during tidal breathing.<br>* Other names: PFP;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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19F MRI, ventilation, pediatrics