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Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

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Abstract

Background

Hyperpolarized 129Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed.

Objective

To assess the feasibility, safety and tolerability of hyperpolarized 129Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis.

Materials and methods

Seventeen healthy control subjects (ages 6–15 years, 11 boys) and 11 children with cystic fibrosis (ages 8–16 years, 4 boys) underwent 129Xe MRI, receiving up to three doses of 129Xe gas prepared by either a commercially available or a homebuilt 129Xe polarizer. Subject heart rate and SpO2 were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI.

Results

All children tolerated multiple doses of 129Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO2 (mean –6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO2 values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following 129Xe MRI, but all were deemed unrelated to the study.

Conclusion

The feasibility, safety and tolerability of 129Xe MRI has been assessed in a small group of children as young as 6 years. SpO2 changes were consistent with the expected physiological effects of a short anoxic breath-hold, and other mild side effects were consistent with the known anesthetic properties of xenon and with previous safety assessments of 129Xe MRI in adults. Hyperpolarized 129Xe is a safe and well-tolerated inhaled contrast agent for pulmonary MR imaging in healthy children and in children with cystic fibrosis who have mild to moderate lung disease.

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Acknowledgments

The authors would like to acknowledge Bastiaan Driehuys, Leslie Korbee, Jenny Jeffries, Lisa McCord, Colleen Murphy and Jeanne Dahlquist for regulatory assistance; Laurie Vanderah, Beth Decker and Emily Bell for subject monitoring; Matthew Lanier, Brynne Williams and Lacey Haas for subject scanning; Dan Dwyer of Teleflex Inc. for the gift of the custom gas-delivery mouthpieces; and Matthew Freeman, Nara Higano, Jim Wild, Charles Dumoulin and the CCHMC IRC Coil Engineering Lab for technical assistance.

This work was supported by the National Institutes of Health (T32HL007752, R01HL116226), Cystic Fibrosis Foundation (CLANCY 15R0), and University of Cincinnati, Center for Clinical and Translational Science and Training (T1 Core, NIH 1UL1TR001425-01).

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Authors and Affiliations

  1. Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave., MLC 5033, Cincinnati, OH, 45229, USA

    Laura L. Walkup, Robert P. Thomen, Teckla G. Akinyi, Erin Watters, Kai Ruppert, Jason C. Woods & Zackary I. Cleveland

  2. Department of Physics, Washington University in St. Louis, St. Louis, MO, USA

    Robert P. Thomen & Jason C. Woods

  3. Biomedical Engineering Program, University of Cincinnati, Cincinnati, OH, USA

    Teckla G. Akinyi & Zackary I. Cleveland

  4. Division of Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    John P. Clancy

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  1. Laura L. Walkup
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Correspondence to Zackary I. Cleveland.

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Walkup, L.L., Thomen, R.P., Akinyi, T.G. et al. Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. Pediatr Radiol 46, 1651–1662 (2016). https://doi.org/10.1007/s00247-016-3672-1

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