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

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 minutes 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 minutes post inhalation SpO2 values showed no significant difference to 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 to baseline within 2 minutes 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.

Assessing the feasibility of hyperpolarized 129Xe multiple‐breath washout MRI in pediatric cystic fibrosis

“…Isotopically enriched 129 Xe (83%) was polarized to approximately 15% (Model 9800; Polarean, Durham, North Carolina) and dispensed into a 1‐L Tedlar bag (Jensen Inert Products, Coral Springs, Florida). To avoid the anesthetic effects of Xe, the HP 129 Xe dose was set to 10% of total lung capacity, as measured using plethysmography, and balanced to 1 L with medical‐grade N 2 .…”

Improved pulmonary 129Xe ventilation imaging via 3D‐spiral UTE MRI

“…Hyperpolarized 129 Xe ventilation imaging quantifies regional ventilation and is sensitive to airway obstruction in a wide variety of diseases . The technique is safe and well‐tolerated for many populations, including pediatrics . Ventilation imaging relies on obtaining reliable, spin density–weighted images to quantify xenon regionally in the lung.…”

Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients

“…Several groups have performed HP 3 He MRI in CF patients (mostly adults) in order to investigate regional defects in ventilation (13–16), HP gas repeatability (17,18), longitudinal ventilation changes (19), and treatment efficacy (20–23). Use of 129 Xe in pediatrics is more restricted than 3 He due to its slightly higher Ostwald solubility (ratio of gas volume absorbed by a liquid to the liquid volume) and thus greater anesthetic effect at high doses, but recent studies have shown that single-breath- holds of sub-anesthetic doses of Xe present no safety concerns in adults (24) or children (25). Because of the increasing cost and scarcity of 3 He, HP gas research has recently shifted focus toward 129 Xe (26, 27), and indeed, there is some evidence that 129 Xe may be more sensitive than 3 He to early functional deficits (26) but CF research in pediatrics with HP 129 Xe MRI has not been reported.…”