Hyperpolarized 129Xe MRI ventilation in pediatric cystic fibrosis lung disease: safety and sensitivity
Laura L Walkup1, Robert P Thomen1,2, Teckla Akinyi1,3, Wolfgang Loew4, Kai Ruppert1, John P Clancy5, Zackary I Cleveland1, and Jason C Woods1

1Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 2Department of Physics, Washington University in St. Louis, St. Louis, MO, United States, 3Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, 4Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 5Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Synopsis

We demonstrate hyperpolarized 129Xe MRI in healthy pediatric control subjects and cystic fibrosis patients as young as age 7, for the first time. Subjects experienced a transient nadir in SpO2 that quickly returns to baseline with normal breathing. Despite having similarly high lung function (i.e., normal FEV1), CF patients had nearly 4-fold increase in 129Xe ventilation defect volume compared to their healthy peers, with statistical significance. Importantly, ventilation defects were present even in CF patients with FEV1 near or exceeding 100% predicted, suggesting that 129Xe MRI is more sensitive to early CF lung disease than traditional clinical spirometry.

Purpose

While the safety, tolerability, and efficacy of hyperpolarized (HP) 129Xe has been reported in adults,1, 2 similar metrics for pediatric subjects have not been reported. The purpose of this study was both to evaluate the safety and tolerability of hyperpolarized 129Xe MRI in pediatric patients and to assess the sensitivity of 129Xe ventilation MRI to early/mild lung disease in clinically-healthy cystic fibrosis (CF) patients with high forced expiratory volume in 1 second (FEV1). We hypothesize that: 1) HP 129Xe gas is a safe inhaled contrast agent for pediatric pulmonary imaging, 2) 129Xe MRI can visualize and quantify ventilation abnormalities in early CF lung disease, and 3) 129Xe ventilation defect volume is more sensitive to impaired lung function than traditional FEV1 in young CF patients.

Methods

Hyperpolarized 129Xe MRI was acquired in 11 cystic fibrosis patients (8-16 y.o.; 4M/7F; FEV1 72-120% predicted) and 15 healthy control subjects (7-15 y.o.; 11M/4F; FEV1 89-127% predicted) on a 3T Philips Achieva MRI scanner using a homebuilt saddle coil3 and hyperpolarized gas prepared from our Center’s homebuilt polarizer4 or a commercially-available polarizer (Polarean Inc., Durham, NC). Two doses were administered: calibration (~250 cc Xe diluted to ~500 cc with N2) and ventilation (either 1/12th [n=5 initial controls] or 1/6th [n=21] of the subject’s predicted total lung capacity5). During the imaging session, SpO2 and heart-rate were recorded at three time-points (immediately post-inhalation, nadir SpO2, and 2 minutes post-inhalation) and compared to resting baseline values. Central nervous system (CNS) effects were assessed at the time of scanning. 129Xe ventilation defect percentage (VDP) was calculated using a threshold of <60% mean whole lung 129Xe signal and compared to FEV1,6 which was acquired within 15 days of the MRI.

Results

Safety: Relative to baseline, all subjects experienced a SpO2 nadir after receiving Xe gas (calibration: -2.7 ± 2.7%, p = 2.7x10-5 and imaging: -5.5 ± 6.4%, p=4.8x10-4). There were no significant SpO2 differences at 2-minute post-inhalation relative to baseline (calibration: p=0.13, imaging: p=0.07). The magnitude of the SpO2 nadir was not significantly different between controls and CF patients for either calibration (control: -2.6±2.4%, CF: -2.8±3.3%, p=0.84) or imaging doses (control: -4.6±4.2%, CF: -6.5±8.5%, p=0.51), and there were no significant changes in heart-rate throughout the study for any time-point or group comparisons (p ≥ 0.20). All CNS effects were mild, consistent with the anesthetic properties of xenon (e.g., tingling, dizziness, euphoria), and resolved quickly (<30s) after breathing room air.

129Xe ventilation: Compared to controls, CF patients had a significantly elevated VDP (CF: 18.2±10.1%, controls 5.1±2.6%, p =0.0024), ranging between 4.6% and 39%. All controls demonstrated homogeneous ventilation and low VDP. The pattern of 129Xe ventilation defects varied greatly across the CF patients (Figure 1); some CF subjects had homogeneous ventilation resembling that of the controls and low VDP, while others had large defects and correspondingly high VDP. There were no significant differences in FEV1 between CF and control groups (CF 98±16.0%, controls 103±10.8%, p=0.35).

Discussion

129Xe MRI was well tolerated by all subjects and generated no unexpected adverse effects. SpO2 decreases were consistent with expected behavior following anoxic breath-holds and resolved quickly as did all CNS effects; these results are consistent with previous adult studies. Importantly, control versus CF group separation was clear and significant with 129Xe VDP and not with FEV1, suggesting 129Xe VDP may be more sensitive to early CF lung disease than traditional spirometry.

Conclusion

To our knowledge, this study is the first assessment of the safety of 129Xe MRI in children and also the first measurement of the sensitivity of 129Xe MRI to detect ventilation deficiencies in early CF lung disease. We found that 129Xe MRI can spatially resolve and quantify ventilation defects in young CF patients-- even in clinically-healthy CF patients with high (≥85%) FEV1s. Furthermore, as a non-ionizing imaging modality, 129Xe MRI VDP can act as an outcome measure for the individualized longitudinal assessment of CF lung disease progression and therapeutic efficacy.

Acknowledgements

No acknowledgement found.

References

1. Driehuys, B., S. Martinez-Jimenez, Z.I. Cleveland, et al., Chronic Obstructive Pulmonary Disease: Safety and Tolerability of Hyperpolarized Xe-129 MR Imaging in Healthy Volunteers and Patients. Radiology, 2012. 262(1): p. 279-289.

2. Shukla, Y., A. Wheatley, M. Kirby, et al., Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. Acad Radiol, 2012. 19(8): p. 941-51.

3. Loew, W., R. Thomen, R. Pratt, et al., A Volume Saddle Coil for Hyperpolarized 129Xe Lung Imaging. Proc. Intl. Soc. Mag. Reson. Med, 2015. 23: p. 1507.

4. Walkup, L., N. Higano, T. Ellis-Caleo, et al., Scaling-up an "open-source" 129Xe hyperpolarizer for human pulmonary imaging applications, in Experimental Nuclear Magnetic Resonance Conference. 2014: Boston, MA.

5. Stocks, J. and P.H. Quanjer, Reference values for residual volume, functional residual capacity and total lung capacity. ATS Workshop on Lung Volume Measurements. Official Statement of The European Respiratory Society. Eur Respir J, 1995. 8(3): p. 492-506.

6. Thomen, R.P., A. Sheshadri, J.D. Quirk, et al., Regional ventilation changes in severe asthma after bronchial thermoplasty with (3)He MR imaging and CT. Radiology, 2015. 274(1): p. 250-9.

Figures

Figure 1: Hyperpolarized 129Xe MRI in three pediatric subjects (top row, control subject; middle and bottom rows, two CF patients).

Table 1: Summary of FEV1% predicted, 129Xe ventilation defect percentage, and baseline and 2-minute post-imaging SpO2 values for pediatric control and CF patients.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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