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

Background Hyperpolarized Xe-129 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 Xe-129 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 Xe-129 measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (ven(def + 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 ven(def + low) was 57.8 +/- 8.4%, bar(%ref) was 73.2 +/- 19.6%, and RBC%ref was 36.5 +/- 13.6%. Following treatment, ven(def + 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 ven(def + 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 Xe-129 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

Automated summary

Hyperpolarized Xe-129 MRI is a useful tool for assessing pulmonary gas exchange function in COPD patients. This study found that LABA/LAMA therapy tended to improve ventilation in subjects with relatively preserved barrier uptake and DLCO, but may reveal RBC transfer defects in newly ventilated regions. The baseline measurements of barrier uptake and DLCO were correlated with the degree of post-treatment change in ventilation defects.