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

Abstract

Background Hyperpolarized 129Xe magnetic resonance imaging (MRI) provides a non‐invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown. Purpose To characterize changes in 129Xe gas transfer function following administration of an inhaled long‐acting beta‐agonist/long‐acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator. Study Type Prospective. Population Seventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy. Field Strength/Sequences Dedicated ventilation imaging used a multi‐slice 2D gradient echo sequence. Three‐dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1‐point Dixon sequence. Imaging was acquired at 3 T. Assessment 129Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (vendef + low) and by barrier uptake and RBC transfer relative to a healthy reference population (bar%ref and RBC%ref). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO), were also performed before and after treatment. Statistical Tests Paired t‐test, Pearson correlation coefficient (r). Results Baseline vendef + low was 57.8 ± 8.4%, bar%ref was 73.2 ± 19.6%, and RBC%ref was 36.5 ± 13.6%. Following treatment, vendef + low decreased to 52.5 ± 10.6% (P < 0.05), and improved in 14/17 (82.4%) of subjects. However, RBC%ref decreased in 10/17 (58.8%) of subjects. Baseline measurements of bar%ref and DLCO were correlated with the degree of post‐treatment change in vendef + low (r = −0.49, P < 0.05 and r = −0.52, P < 0.05, respectively). Conclusion LABA/LAMA therapy tended to preferentially improve ventilation in subjects whose 129Xe barrier uptake and DLCO were relatively preserved. However, newly ventilated regions often revealed RBC transfer defects, an aspect of lung function opaque to spirometry. These microvasculature abnormalities must be accounted for when assessing the effects of LABA/LAMA therapy. Level of Evidence 1 Technical Efficacy Stage 4

Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial

“…Nevertheless, it is known that IND/GLY improves COPD symptoms and lung function, and the 3 He and 1 H MRI-demonstrated changes in ventilation and perfusion may provide a mechanism to better explain the established clinical profile of dual bronchodilation. Consistent findings from a slightly smaller study using 129 Xe MRI support this notion [ 28 ].…”

“…Hence, in our study we were able to show that a broad and heterogeneous population of COPD patients benefit from dual bronchodilation in terms of improvements in ventilation homogeneity and V/Q mismatch. Apart from these fundamental methodological differences, the differing results between that study [ 28 ] and ours may also relate to the definition of the clinical cohort such as excluding patients with gross emphysema in our work. While degree of emphysema was not correlated with improvements in ventilation parameters following IND/GLY, it must be noted that our study does not determine whether patients with gross emphysema would benefit in a similar fashion.…”

“…The MRI approach demonstrated sufficient sensitivity to elucidate the pharmacodynamic action of IND/GLY. Hyperpolarized gas imaging may help to sensitively detect ventilation abnormalities in different phenotypes of COPD as recently shown for patients with more bronchitis-predominant phenotype [ 28 ].…”

“…Mummy et al [ 28 ] assessed regional gas exchange 129 Xe MRI alone in patients with COPD, before and after combination bronchodilator, where ventilation increased after bronchodilator but regional gas exchange did not. The gas exchange 129 Xe imaging method employed by Mummy et al measures the ratio of 129 Xe in the red blood cells to 129 Xe in the ventilated airspaces.…”

Disease activity in COPD: time to make imaging biomarkers a PET project?

“…Paired inspiratory-expiratory CT may also be analysed for indirect functional biomarkers [ 20 ], such as small airways disease or gas trapping [ 21 , 22 ], and lung biomechanics [ 23 ]. In contrast, MRI using inhaled hyperpolarised gases ( 3 He or 129 Xe) provides direct functional information in the form of pulmonary ventilation distribution and gas exchange [ 24 ] that are highly abnormal and regionally heterogeneous in patients with COPD [ 25 , 26 ]. An important advantage of imaging over other approaches to biomarker discovery is the ability to capture regional heterogeneity in lung structure, function and physiology that is characteristic of COPD.…”