The assessment of short- and long-term changes in lung function in cystic fibrosis using¹²⁹Xe MRI

Abstract

<jats:sec><jats:title>Introduction</jats:title><jats:p><jats:sup>129</jats:sup>Xe ventilation MRI is sensitive to detect early CF lung disease and response to treatment. <jats:sup>129</jats:sup>Xe-MRI could play a significant role in clinical trials and patient management. Here we present data on the repeatability of imaging measurements and their sensitivity to longitudinal change.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>29 children and adults with CF and a range of disease severity were assessed twice, a median [IQR] of 16.0 [14.4,19.5] months apart. Patients performed <jats:sup>129</jats:sup>Xe-MRI, lung clearance index (LCI), body plethysmography and spirometry at both visits. Eleven patients repeated <jats:sup>129</jats:sup>Xe-MRI in the same session to assess the within-visit repeatability. The ventilation defect percentage (VDP) was the primary metric calculated from <jats:sup>129</jats:sup>Xe-MRI.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>At baseline, mean (<jats:sc>sd</jats:sc>) age=23.0 (11.1) years and FEV<jats:sub>1</jats:sub> z-score=−2.2 (2.0). Median [IQR] VDP=9.5 [3.4,31.6]%, LCI=9.0 [7.7,13.7]. Within-visit and inter-visit repeatability of VDP was high. At 16 months there was no single trend of <jats:sup>129</jats:sup>Xe-MRI disease progression. Visible <jats:sup>129</jats:sup>Xe-MRI ventilation changes were common, which reflected changes in VDP. Based on the within-visit repeatability, a significant short-term change in VDP is &gt;±1.6%. For longer-term follow up, changes in VDP of up to ±7.7% can be expected, or ±4.1% for patients with normal FEV<jats:sub>1</jats:sub>. No patient had a significant change in FEV<jats:sub>1</jats:sub>, however 59% had change in VDP &gt;±1.6%. In patients with normal FEV<jats:sub>1</jats:sub>, there were significant changes in ventilation and in VDP.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:sup>129</jats:sup>Xe-MRI is a highly effective method for assessing longitudinal lung disease in patients with CF. VDP has great potential as a sensitive clinical outcome measure of lung function and endpoint for clinical trials.</jats:p></jats:sec>

The effect of acute maximal exercise on the regional distribution of ventilation using ventilation MRI in CF

“…For most patients in the current study however (85%), the CPET caused a visible change in ventilation. Given the high intra-session repeatability of 129 Xe VDP (25), this suggests that the changes we observed in VDP and in the distribution of ventilation, relate to the underlying CF pathophysiology, and in part are likely a consequence of mucus movement in the airways. Change in VDP was greater than the intra-session repeatability of VDP, and therefore significant, for 45% of the patients assessed with 129 Xe.…”

Regional Gas Exchange Measured by 129Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease

“…A contemporaneous CT could provide confirmation of disease phenotype and aid in the interpretation of 129 Xe findings, as illustrated by recent work by Myc et al 20 Third, the repeatability of 129 Xe MRI ventilation measurements in COPD has not been well characterized, limiting our ability to determine a clinically meaningful change in ventilation metrics. Previous studies have showed high repeatability for 129 Xe measurements of VDP in asthma 4 and cystic fibrosis, 42 and analogous studies are needed for COPD. Further, while the RBC to barrier ratio is known to be more robust to lung inflation than those measurements taken individually, 43 it is not possible to tell whether changes in this ratio are the result of changes in RBC, barrier, or both; thus we have elected here to report the two as separate measurements.…”

In vivo methods and applications of xenon-129 magnetic resonance

“…129 Xe ventilation MRI response to therapy has been demonstrated in: patients with asthma after bronchodilator inhalation [163] and bronchial thermoplasty [312] , children with CF after pulmonary exacerbation and subsequent treatment with intravenous antibiotics [170] , patients with CF after acute maximal exercise [313] , patients with bronchial stenosis after airway stent placement [171] , and a patient with adenocarcinoma after radiotherapy [172] . In a study monitoring response to antibiotics in children with CF, 129 Xe VDP showed the largest relative improvement of all outcome measures [170] , and 129 Xe ventilation MRI has been shown to be a sensitive method to assess longitudinal lung disease in children and adults with CF [158] , [314] . Increased 129 Xe ventilation heterogeneity at low lung inflation levels, consistent with airway closure, has been noted in healthy elite divers who were able to exhale beyond the residual volume of the lungs [173] , and in healthy volunteers [174] , emphasising the need to control for lung inflation level to ensure reliable longitudinal ventilation imaging.…”