Journal article
Multi-center Study of Hyperpolarized Xenon MRI in Children with Cystic Fibrosis Following Initiation of CFTR Modulator Therapy (HyPOINT)
Annals of the American Thoracic Society, Vol.22(12), pp.1891-1899
12/2025
DOI: 10.1513/AnnalsATS.202501-028OC
PMCID: PMC12915570
PMID: 40795189
Abstract
Elexacaftor/tezacaftor/ivacaftor (ETI) has significantly improved lung function in people with cystic fibrosis (CF), prompting the need for outcome measures that can detect mild disease. In this new era of CFTR modulator therapy, more sensitive endpoints are required to evaluate the progression of early lung disease and to determine the efficacy of new CF therapies. Prior to the availability of highly effective therapies 129Xenon magnetic resonance imaging (Xe MRI) was shown to be more sensitive to regional ventilation changes compared to spirometry.
To evaluate the longitudinal changes in pulmonary function and Xe-MRI outcomes after treatment with ETI in children and young people with CF.
Lung function was assessed longitudinally at baseline 1, 6, and 12 months following ETI treatment initiation in children and young people with CF between the ages of 6 and 18 years at four study sites. Ventilation defect percentage (VDP), reader-defect percentage (RDP), Lung Clearance Index (LCI) and Forced Expiratory Volume in 1 second (FEV1) were reported.
A total of 28 participants were enrolled; 25 completed at least baseline and one-month measurements. All four measures (RDP, VDP, LCI and FEV1) improved at one month after ETI initiation with a mean (standard deviation) absolute change of -1.2 (1.7) in LCI, 6.9 (12.3) in FEV1, -4.3 (4.8) in VDP and --7.8 (9.6) in RDP, respectively. Xe MRI outcomes (RDP and VDP) showed the largest relative treatment effects with mean relative improvements of 43% and 72%, respectively. One third of participants (8/25) had improvements in VDP and RDP but did not show improvements in FEV1.
Xe MRI captures sustained ventilation improvements following ETI initiation. Xe MRI metrics may provide a suitable endpoint for future interventional trials-particularly for people with CF with mild lung disease.
Details
- Title: Subtitle
- Multi-center Study of Hyperpolarized Xenon MRI in Children with Cystic Fibrosis Following Initiation of CFTR Modulator Therapy (HyPOINT)
- Creators
- Felix A Ratjen - University of TorontoSanja Stanojevic - Hospital for Sick ChildrenSamal Munidasa - Cincinnati Children's Hospital Medical CenterDavid Roach - Cincinnati Children's Hospital Medical CenterJaime Mata - University of VirginiaDeborah K Froh - University of VirginiaBrandon Zanette - Hospital for Sick ChildrenGiles Santyr - Hospital for Sick ChildrenSean B Fain - University of IowaMichael J Rock - University of Wisconsin–MadisonLaura L Walkup - Cincinnati Children's Hospital Medical CenterJason C Woods - Cincinnati Children's Hospital Medical Center
- Resource Type
- Journal article
- Publication Details
- Annals of the American Thoracic Society, Vol.22(12), pp.1891-1899
- DOI
- 10.1513/AnnalsATS.202501-028OC
- PMID
- 40795189
- PMCID
- PMC12915570
- NLM abbreviation
- Ann Am Thorac Soc
- ISSN
- 2329-6933
- eISSN
- 2325-6621
- Publisher
- AMER THORACIC SOC; NEW YORK
- Grant note
- Cystic Fibrosis Foundation: WOODS19A0 University of Cincinnati Center for Clinical and Translational Science and Training (National Center for Advancing Translational Sciences): UL1TR001425
Supported by Cystic Fibrosis Foundation grant WOODS19A0 and University of Cincinnati Center for Clinical and Translational Science and Training (National Center for Advancing Translational Sciences grant UL1TR001425) .
- Language
- English
- Electronic publication date
- 08/12/2025
- Date published
- 12/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Health, Sport, and Human Physiology
- Record Identifier
- 9984946837802771
Metrics
4 Record Views