Hyperpolarized Helium 3 MRI in Mild-to-Moderate Asthma: Prediction of Postbronchodilator Reversibility

Abstract

Background: Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition. Purpose: To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3 He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV 1) reversibility Materials and Methods: Spirometry and hyperpolarized 3 He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) and pre-and postbronchodilator evaluations at follow-up (November 2016 to June 2017). FEV 1 and MRI ventilation defects, quantified as ventilation defect volume (VDV), were compared between visits by using paired t tests. Participants were dichotomized by postbronchodilator change in FEV 1 at follow-up, and differences between reversible and notreversible groups were determined by using unpaired t tests. Multivariable models were generated to explain postbronchodilator FEV 1 reversibility at follow-up. Results: Eleven participants with asthma (mean age, 42 years 6 9 [standard deviation]; seven men) were evaluated at baseline and after mean 78 months 6 7. Medications, exacerbations, FEV 1 (76% predicted vs 76% predicted; P = .91), and VDV (240 mL vs 250 mL; P = .92) were not different between visits. In eight of 11 participants (73%), MRI ventilation defects at baseline were at the same location in the lung at follow-up MRI. In the remaining three participants (27%), MRI ventilation defects worsened at the same lung locations as depicted at baseline methacholine-induced ventilation. At follow-up, postbronchodilator FEV 1 was not reversible in six of 11 participants; the concentration of methacholine to decrease FEV 1 by 20% (PC 20) was greater in FEV 1irreversible participants at follow-up (P = .01). In a multivariable model, baseline MRI VDV helped to predict postbronchodilator reversibility at follow-up (R 2 = 0.80; P , .01), but PC 20 , age, and FEV 1 did not (R 2 = 0.63; P = .15). Conclusion: MRI-derived, spatially persistent ventilation defects predict postbronchodilator reversibility 78 months 6 7 later for participants with mild-to-moderate asthma in whom there were no changes in lung function, medication, or exacerbations.

3D Magnetic Resonance Spirometry

“…In spontaneous breathing, standard spirometry loses all sensitivity to ventilation defects and any disease specificity as the global flow-volume loops are generally affected only when the lung is challenged to the limit of its abilities. Even at the high and low pressures that are reached during coached forced breathing, FVC and FEV 1 may fail revealing or staging lung dysfunction as it was brought to light early on by hyperpolarized gas MRI when the recorded percentage of ventilation defects did not always correlate with standard spirometry [20][21][22][23] . In 3D MR Spirometry, because of the long total scan time, only spontaneous breathing can be reasonably performed by the patient.…”

Structure and function of small airways in asthma patients revisited

“…It has been shown that the presence of ventilation defects, frequently observed in patients with asthma, is due to heterogeneous airway closure or narrowing of small airways [145]. In several studies it was shown that ventilation defects are not seen randomly but they might be predefined [146] or a result of remodelling [147]. Furthermore, it has been shown that ventilation defects persist over time [146,148,149].…”

“…Therefore, some sort of partial or intermittent closure must be present in the patients with persisting ventilation defects or these areas are ventilated through collateral ventilation [150]. Ventilation defects are associated with disease severity [144,147,151,152], lung clearance index [152] and spirometry [144,151].…”

FEV1and MRI ventilation defect reversibility in asthma and COPD

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The underlying pathophysiological determinants of asthma and COPD are related in complex ways. Importantly however, post-bronchodilator forced expiratory volume in 1 s (FEV 1 ) reversibility may occur in approximately 50% of COPD patients [1], whilst epidemiological [2] and magnetic resonance imaging (MRI) studies [3] suggest that, in asthma patients, FEV 1 reversibility may diminish over time. As compared to patients with asthma or COPD alone, patients with co-existing asthma and COPD report worse clinical outcomes [4] and increased healthcare costs [5] and burden [4,5].Hyperpolarised 3 He and 129 Xe MRI studies have reported clinically relevant post-bronchodilator improvements in MRI ventilation defects in patients with asthma [6] and COPD [7], independent of FEV 1 reversibility.

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“…To better understand bronchodilator reversibility in patients with a diagnosis of asthma or COPD, we retrospectively evaluated spirometry and hyperpolarised 3 He MRI measurements in participants with asthma (age ⩾40 years, <1 pack-year smoking history) and COPD (age 60-85 years, >10 pack-years smoking history). We expected that MRI would detect post-bronchodilator reversibility in participants in whom there was negligible post-bronchodilator FEV 1 reversibility, thereby providing a small and large airway quantitative functional measurement with more enhanced sensitivity to small airways disease and greater dynamic range than FEV 1 .…”