Dynamic contrast-enhanced magnetic resonance imaging of the lung reveals important pathobiology in idiopathic pulmonary fibrosis

Abstract

Introduction: Evidence suggests that abnormalities occur in the lung microvasculature in idiopathic pulmonary fibrosis (IPF). We hypothesised that dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) could detect alterations in permeability, perfusion and extracellular extravascular volume in IPF, thus providing in vivo regional functional information not otherwise available.

Methods: Healthy controls and IPF subjects underwent DCE-MRI of the thorax using a dynamic volumetric radial sampling sequence and administration of gadoterate meglumine at a dose of 0.1 mmol·kg^-1 at 2 mL·s^-1. Model-free analysis of signal intensity versus time curves in regions of interest from a lower, middle and upper axial plane, a posterior coronal plane and the whole lung yielded parameters reflective of perfusion and permeability (peak enhancement and rate of contrast arrival (k_washin)) and the extracellular extravascular space (rate of contrast clearance (k_washout)). These imaging parameters were compared between IPF and healthy control subjects, and between fast/slow IPF progressors.

Results: IPF subjects (n=16, 56% male, age (range) 67.5 (60-79) years) had significantly reduced peak enhancement and slower k_washin in all measured lung regions compared to the healthy volunteers (n=17, 65% male, age (range) 58 (51-63) years) on unadjusted analyses consistent with microvascular alterations. k_washout, as a measure of the extravascular extracellular space, was significantly slower in the lower lung and posterior coronal regions in the IPF subjects consistent with an increased extravascular extracellular space. All estimates were attenuated after adjusting for age. Similar trends were observed, but only the associations with k_washin in certain lung regions remained statistically significant. Among IPF subjects, k_washout rates nearly perfectly discriminated between those with rapidly progressive disease versus those with stable/slowly progressive disease.

Conclusions: DCE-MRI detects changes in the microvasculature and extravascular extracellular space in IPF, thus providing in vivo regional functional information.

FIGURE 1

Dynamic curves of the lung parenchyma from healthy controls (HC; n=17) and idiopathic pulmonary fibrosis (IPF) subjects (n=16) computed as percentage signal intensity (SI) change relative to baseline over time. The group-averaged the dynamic curves from posterior coronal regions of interest are shown. Shaded area indicates mean±1 sem.

FIGURE 2

Comparison of model-free dynamic contrast-enhanced magnetic resonance imaging parameters between the healthy control (HC) group and the idiopathic pulmonary fibrosis (IPF) group. The parameters were derived from the dynamic curves measured from four regions of interest in the lung parenchyma, including upper, middle and lower regions of the lung defined on axial slices as well as on a coronal slice posterior to the heart and across the descending aorta in addition to the whole lung. Results displayed as boxplots with solid line denoting median, box denoting 25–75th percentiles and whiskers denoting minimum to maximum values. Unadjusted p-values obtained from univariable linear regression models are shown. *: p<0.05, **: p<0.01, ***: p<0.001. PE: peak enhancement; TTP: time to peak; k_washin: rate of contrast arrival; k_washout: rate of contrast clearance; AUC₆₀: area under the dynamic curve in the first 60 s.

FIGURE 3

Representative a) dynamic curves and parametric maps of b) peak enhancement, c) rate of contrast arrival (k_washin), and d) rate of contrast clearance (k_washout) from a healthy control subject, an idiopathic pulmonary fibrosis (IPF) patient with stable/slow disease progression and an IPF patient with rapid disease progression. e) For each IPF patient, a coronal slice from high-resolution computed tomography (HRCT) obtained within 6 months prior to magnetic resonance imaging is shown. When compared to b, c, and d, abnormalities in peak enhancement, k_washin and k_washout are not limited to areas of fibrosis detected upon HRCT. SI: signal intensity.

FIGURE 4

Comparison of rate of contrast clearance (k_washout) between idiopathic pulmonary fibrosis patient subgroups: stable/slow progression (n=10) versus rapid progression (n=5). Results displayed as boxplots with solid line denoting median, box denoting 25–75th percentiles and whiskers denoting minimum to maximum values. p-values obtained from Wilcoxon rank sum test are shown. *: p<0.05, **: p<0.01, ***: p<0.001.