Assessing 129Xe multi-breath washout MRI response to elexacaftor/tezacaftor/ivacaftor intervention in pediatric CF

Faiyza Alam; Samal Munidasa; Brandon Zanette; Sharon Braganza; Daniel Li; Renee Jensen; Marie-Pier Dumas; Felix Ratjen; Giles Santyr

doi:10.1016/j.jcf.2024.09.021

Assessing ¹²⁹Xe multi-breath washout MRI response to elexacaftor/tezacaftor/ivacaftor intervention in pediatric CF

J Cyst Fibros. 2024 Sep 30:S1569-1993(24)01789-2. doi: 10.1016/j.jcf.2024.09.021. Online ahead of print.

Authors

Faiyza Alam¹, Samal Munidasa², Brandon Zanette³, Sharon Braganza³, Daniel Li³, Renee Jensen⁴, Marie-Pier Dumas⁵, Felix Ratjen⁶, Giles Santyr²

Affiliations

¹ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: faiyza.alam@sickkids.ca.
² Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
³ Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.
⁴ Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
⁵ Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada; Clinical Epidemiology & Health Care Research, University of Toronto, Toronto, ON, Canada.
⁶ Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada; Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

PMID: 39353741
DOI: 10.1016/j.jcf.2024.09.021

Abstract

Background: Monitoring multiple-breath washout (MBW) of a xenon tracer using magnetic resonance imaging (MBW Xe-MRI) provides quantitative regional measures of gas washout (fractional ventilation, FV) and spatial ventilation heterogeneity (coefficient of variation, CoV_FV) in pediatric CF lung disease, but has yet to be evaluated in an interventional setting.

Methods: 12 pediatric CF participants (median age 15.3 ± 2 years) completed MBW Xe-MRI, pulmonary function tests (PFTs) (spirometry, N₂ MBW for lung clearance index (LCI)) and single-breath Xe-MRI ventilation defect percent (VDP) measurements at baseline and 1-month post-initiation of elexacaftor/tezacaftor/ivacaftor (ETI) therapy. FV maps were calculated from MBW Xe-MRI washout images, and CoV_FV maps were derived from FV maps. Significant changes between visits were determined using a paired Wilcoxon signed-rank test. For correlations between absolute changes, Pearson's correlation was used.

Results: All measures changed significantly 1-month post-ETI therapy compared to baseline. For MRI metrics, median [IQR] VDP was significantly (P < 0.001) lower at 1 month (8.0 [3.7 12.4]) compared to baseline (17.8 [8.3 22.5]), FV was significantly (P < 0.05) higher at 1 month (0.42 [0.41 0.46]) compared to baseline (0.38 [0.33 0.44]), and CoV_FV was significantly (P < 0.001) lower at 1 month (0.06 [0.05 0.07]) compared to baseline (0.09 [0.08 0.12]). Both absolute and relative differences in CoV_FV and LCI were found to correlate highly (R = 0.92, P < 0.0001 and R = 0.91, P < 0.0001, respectively).

Conclusions: Functional information derived from MBW Xe-MRI, particularly CoV_FV, can be used to assess regional lung function in pediatric CF patients in an interventional setting and may be complementary to VDP and pulmonary function tests.

Keywords: Fractional ventilation; Hyperpolarized (129)Xe; Lung clearance index; Multiple-breath washout; Pediatric; elexacaftor/tezacaftor/ivacaftor.