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Comparison of Phase-Resolved Functional Lung (PREFUL) MRI and Hyperpolarized 129Xe MRI in Pediatric Cystic Fibrosis
Marcus J. Couch1,2, Jonathan H. Rayment3, Robert Grimm4, Andreas Voskrebenzev5,6, Jens Vogel-Claussen5,6, Felix Ratjen1,7, and Giles Santyr1,2

1Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada, 2Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, 3Division of Respiratory Medicine, British Columbia Children’s Hospital, Vancouver, BC, Canada, 4MR Application Predevelopment, Siemens Healthcare, Erlangen, Germany, 5Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany, 6Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany, 7Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada

Synopsis

Hyperpolarized 129Xe MRI provides robust measurements of ventilatory function through the measurement of the ventilation defect percent (VDP). Recent progress in 1H-based free-breathing techniques (phase-resolved functional lung; PREFUL) allows for the calculation of fractional ventilation maps, which can be similarly processed to calculate VDP. While hyperpolarized 129Xe is an established research technique, PREFUL MRI is simple to implement on any MRI scanner and therefore has good potential for use in future clinical trials in cystic fibrosis (CF). In this study, VDP measurements performed using hyperpolarized 129Xe and PREFUL MRI were compared and correlated with pulmonary function tests in pediatric CF.

Introduction

Free-breathing 1H-based functional lung imaging techniques, such as Fourier Decomposition (FD), provide maps related to ventilation and perfusion.1 Additional post-processing steps can be applied to calculate fractional ventilation (FV) from the free-breathing 1H images using a modified FD reconstruction2 or Phase-Resolved Functional Lung (PREFUL) MRI.3 Hyperpolarized (HP) 129Xe MRI is an established lung imaging technique that is feasible in children with cystic fibrosis (CF)4, and measurements of the ventilation defect percent (VDP), defined as the fraction of unventilated lung, can provide a more sensitive indicator of mild lung disease than spirometric indices, such as the forced expiratory volume in one second (FEV1).5 HP 129Xe VDP is strongly correlated with the lung clearance index (LCI), a measure of ventilation heterogeneity derived from nitrogen multiple breath washout (MBW).6-8 Since HP 129Xe MRI is not widely available, 1H-based functional lung imaging approaches are desirable; however, the application of PREFUL MRI in pediatric CF has been limited to date. The purpose of this study was to compare PREFUL and HP 129Xe MRI and correlate both techniques to LCI and FEV1 in pediatric CF.

Methods

24 pediatric participants were recruited (mean age 13±3 years), including 8 healthy controls, 5 with stable well-controlled CF, and 11 CF patients undergoing a pulmonary exacerbation (PEx) at the time of imaging. 9 of the PEx participants returned for a second imaging visit after 2 weeks of treatment. Standard pulmonary function tests were performed, as well as N2 MBW (Exhalyzer D®, EcoMedics AG) to measure LCI (2.5% threshold). Imaging was performed at 3T (MAGNETOM Prisma, Siemens Healthcare) using a flexible 129Xe vest coil (Clinical MR Solutions) and previously described methods.9 Table 1 summarizes the GRE acquisition parameters for the HP 129Xe breath-hold and accompanying breath-hold of N2 for 1H imaging at the same lung volume. Functional 1H MRI was performed by repeating a single central coronal slice TurboFLASH acquisition at a sampling rate of ~3.6 frames per second (Table 1). PREFUL FV maps were calculated using prototype software (MR Lung, Siemens Healthcare)3, and VDP was calculated for both PREFUL and HP 129Xe MRI and using k-means segmentation.9,10

Results

Figure 1 shows a comparison of PREFUL FV maps and HP 129Xe MRI acquired in a representative healthy participant and two CF patients. The HP 129Xe VDP represents a whole lung measurement, and the slice most closely matching the location of the FV map is shown. The healthy and stable CF participants had a low VDP as measured by either PREFUL or HP 129Xe. The CF participant undergoing a PEx had substantial ventilation defects in both the PREFUL and HP 129Xe maps, and these defects improved following treatment. Figure 2 shows that the VDP measurements from both techniques are correlated with one another. Figure 3 shows moderate and significant correlations for both VDP calculation methods compared to LCI. Figure 4 shows similar moderate and significant correlations for both methods compared to FEV1. For the PEx participants that returned for a second visit after treatment, there was a statistically significant difference in HP 129Xe VDP and FEV1, but not for PREFUL VDP and LCI (p = 0.020, 0.008, 0.098, and 0.074 from Wilcoxon matched-pairs tests, respectively).

Discussion

This study demonstrates a correlation between PREFUL and HP 129Xe VDP in pediatric CF, which qualitatively agrees with similar VDP measurements previously performed using HP 3He and FD MRI in adults with chronic obstructive pulmonary disease.11 The differences in defect regions captured in the segmented maps reflect the complementary nature of the two imaging approaches. The good correlation between VDP and LCI for both techniques suggests that imaging provides a sensitive indicator of ventilation heterogeneity, which is especially important in early CF lung disease where FEV1 often appears normal. Previous work in stable CF has shown a stronger correlation between VDP and LCI6; however, this work includes a broader spectrum of CF lung disease (i.e. PEx). For the whole PEx group, PREFUL VDP was unable to detect significant functional changes following treatment for a PEx, which may point to the need for further image quality optimization. On the other hand, the single-slice nature of the PREFUL acquisition does not necessarily capture regions of the lung that are most affected by the treatment.

Conclusions

HP 129Xe and PREFUL MRI are able to provide measures of VDP that are correlated with pulmonary function tests in pediatric CF. PREFUL MRI has a potentially broader applicability in the clinic, since it can be performed on any MRI scanner without inhaled contrast gases, which may be advantageous for young CF patients.

Acknowledgements

The authors would like to thank the following individuals for their help with data collection: Yonni Friedlander, Raymond Hu, Nikhil Kanhere, Krzysztof Kowalik, Andras Lindenmaier, Tammy Rayner, Laura Seed, Ravi Seethamraju, Elaine Stirrat, Ruth Weiss, David Wilson, and Brandon Zanette. We would also like to thank the following sources of funding: The Hospital for Sick Children (Catalyst Grant from the Cystic Fibrosis Centre), Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant (RGPIN 217015-2013), Canadian Institutes of Health Research (CIHR) operating and project grants (MOP 123431, PJT 153099). MJC was funded by a Research Training Competition (Restracomp) Fellowship from the Hospital for Sick Children and a Mitacs Elevate Postdoctoral Fellowship.

References

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Figures

Table 1: Summary of HP 129Xe and 1H MRI acquisition parameters.

Figure 1: Representative images acquired in (a) a healthy participant, (b) a stable CF participant, (c) a CF participant undergoing a pulmonary exacerbation (PEx), and (d) the same PEx participant after 2 weeks of treatment. From left to right, the images show (i) an overlay of the 1H TurboFLASH acquisition and the processed PREFUL FV map, (ii) the segmented FV map showing ventilated areas in green and defect areas in purple, (iii) an overlay of the 1H GRE and HP 129Xe GRE acquisitions, and (iv) the segmented 129Xe image showing ventilated areas in green and defect areas in purple.

Figure 2: Correlation between VDP measurements performed using PREFUL and HP 129Xe MRI. Overall, there was a moderate positive and significant correlation, and the spread of the data points may be due to the single-slice nature of the PREFUL acquisition.

Figure 3: Correlation between VDP and LCI for measurements performed using (left) PREFUL MRI and (right) HP 129Xe MRI. In both cases, there was a moderate positive and significant correlation between VDP and LCI.

Figure 4: Correlation between VDP and FEV1 (as a percentage of the predicted value) for measurements performed using (left) PREFUL MRI and (right) HP 129Xe MRI. In both cases, there was a moderate negative and significant correlation between VDP and FEV1.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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