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Safety of repeated hyperpolarized helium 3 magnetic resonance imaging in pediatric asthma patients

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Abstract

Background

Hyperpolarized helium 3 magnetic resonance imaging (3He MRI) is useful for investigating pulmonary physiology of pediatric asthma, but a detailed assessment of the safety profile of this agent has not been performed in children.

Objective

To evaluate the safety of 3He MRI in children and adolescents with asthma.

Materials and methods

This was a retrospective observational study. 3He MRI was performed in 66 pediatric patients (mean age 12.9 years, range 8–18 years, 38 male, 28 female) between 2007 and 2017. Fifty-five patients received a single repeated examination and five received two repeated examinations. We assessed a total of 127 3He MRI exams. Heart rate, respiratory rate and pulse oximetry measured oxygen saturation (SpO2) were recorded before, during (2 min and 5 min after gas inhalation) and 1 h after MRI. Blood pressure was obtained before and after MRI. Any subjective symptoms were also noted. Changes in vital signs were tested for significance during the exam and divided into three subject age groups (8–12 years, 13–15 years, 16–18 years) using linear mixed-effects models.

Results

There were no serious adverse events, but three minor adverse events (2.3%; headache, dizziness and mild hypoxia) were reported. We found statistically significant increases in heart rate and SpO2 after 3He MRI. The youngest age group (8–12 years) had an increased heart rate and a decreased respiratory rate at 2 min and 5 min after 3H inhalation, and an increased SpO2 post MRI.

Conclusion

The use of 3He MRI is safe in children and adolescents with asthma.

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Acknowledgments

The authors wish to thank the nurse coordinators (Jan Yakey, RN, and Molly Ellertson, RN) and research technologists — Kelly Hellenbrand, RT(R), Sara John RT(R), and Janelle Grogan RT(R) — who supported the safety monitoring, data acquisition and regulatory reporting for the MRI components for the studies in this work. Parts of this work were funded by the National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (NHLBI): U10 HL109168, P01 HL070831 (COAST), R01 HL126771 (SARP), NIH/National Center for Research Resources (NCRR) Pulmonary Imaging Center S10 OD016394. This project was also supported in part by the University of Wisconsin, Department of Radiology, Research and Development Fund, and by the Office of the Vice Chancellor for Research and Graduate Education at the University of Wisconsin–Madison with funding from the Wisconsin Alumni Research Foundation.

Author information

Authors and Affiliations

  1. Department of Radiology, University of Wisconsin-Madison, 111 Highland Ave., 2488 WIMR, Madison, WI, 53705, USA

    Nanae Tsuchiya, Mark L. Schiebler & Sean B. Fain

  2. Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA

    Michael D. Evans

  3. Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA

    Robert V. Cadman & Sean B. Fain

  4. Department of Pediatrics-Allergy, Immunology & Rheumatology, University of Wisconsin-Madison, Madison, WI, USA

    Ronald L. Sorkness, Robert F. Lemanske Jr. & Daniel J. Jackson

  5. Department of Medicine-Allergy, Pulmonary & Critical Care, University of Wisconsin-Madison, Madison, WI, USA

    Ronald L. Sorkness, Daniel J. Jackson, Nizar N. Jarjour & Loren C. Denlinger

Authors
  1. Nanae Tsuchiya
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  2. Mark L. Schiebler
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  3. Michael D. Evans
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  4. Robert V. Cadman
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  5. Ronald L. Sorkness
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  6. Robert F. Lemanske Jr.
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  7. Daniel J. Jackson
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  8. Nizar N. Jarjour
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  9. Loren C. Denlinger
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  10. Sean B. Fain
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Corresponding author

Correspondence to Sean B. Fain.

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Conflicts of interest

The authors of this manuscript declare relationships with the following companies: Mark L. Schiebler, MD, is a shareholder in Healthmyne and Stemina Biomarker Discovery; Sean B. Fain, PhD, receives grant support from GE Healthcare and serves on the scientific advisory board of Xemed.

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Appendices

Appendix 1

Spirometry

For COAST, the spirometry was performed as described in Guilbert et al. [35]. For SARP, spirometry was performed as described in Denlinger et al. [23]. Briefly, spirometry was performed according to American Thoracic Society (ATS)/European Respiratory Society (ERS) standards [36] pre- and post-bronchodilation with albuterol, and expressed as the percentage of predicted values obtained from the Global Lung Function Initiative (GLI) 2012 reference equations [37]. Short- and long-acting bronchodilator medications were held prior to the visits, and post-bronchodilation measurements were obtained after 2 actuations of albuterol for COAST, and after 4-8 actuations for SARP.

Appendix 2

Invalid or missing data

The timing of gas inhalation was decided by technician and there were some cases whose second or third dose was given at the same time or before the vital sign assessment at 2 min or 5 min after the previous dose. We excluded these 29 measurements in 27 exams as invalid data (next dose was given before the 5-min assessment in 19 measurements; next dose was given at same time as the 5-min assessment in 10 measurements; next dose was given at same time as the 2-min assessment in 1 measurement).

There were 12 cases of missing data. All missing data were at 1 h after MRI (blood pressure, 1 case; heart rate, 1 case; respiratory rate, 5 cases; SpO2, 5 cases).

Appendix 3

Minor adverse events

Case 1. A 15-year-old girl complained of feeling dizzy at the time point of 5 min after inhaling a 3rd dose of helium gas. Her vital signs were normal when she was feeling dizzy. She didn’t complain of dizziness after MR exam and was discharged asympomatic.

Case 2. A 15-year-old boy complained of headache at the post-MRI assessment. At that time, his vital signs were normal, and he did not report other symptoms like dizziness or shortness of breath. One hour after discharge, a follow-up call was made and a message was left at home. There were no further reported problems.

Case 3. A 16-year-old girl had multiple recorded measures of hypoxia. The first hypoxia record (SpO2 88%) was remeasured with repositioning of probe pulse oximetry probe and corrected to SpO2 93%, however after that, recorded measures of hypoxia continued over several minutes. Other vitals (heart rate and respiratory rate) were normal and she didn’t complain of any symptoms during this time. The SpO2 recorded at 16 min after the first hypoxia record was 100%. The results of spirometry on the same day of MRI were normal. This 3He MRI examination was her second exam. At the first exam 3 years prior, there were no records of hypoxia.

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Tsuchiya, N., Schiebler, M.L., Evans, M.D. et al. Safety of repeated hyperpolarized helium 3 magnetic resonance imaging in pediatric asthma patients. Pediatr Radiol 50, 646–655 (2020). https://doi.org/10.1007/s00247-019-04604-0

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