MRI pulmonary artery flow detects lung vascular pathology in preterms with lung disease

Abstract

Background: Pulmonary vascular disease (PVD) affects the majority of preterm neonates with bronchopulmonary dysplasia (BPD) and significantly determines long-term mortality through undetected progression into pulmonary hypertension. Our objectives were to associate characteristics of pulmonary artery (PA) flow and cardiac function with BPD-associated PVD near term using advanced magnetic resonance imaging (MRI) for improved risk stratification.

Methods: Preterms <32 weeks postmenstrual age (PMA) with/without BPD were clinically monitored including standard echocardiography and prospectively enrolled for 3 T MRI in spontaneous sleep near term (AIRR (Attention to Infants at Respiratory Risks) study). Semi-manual PA flow quantification (phase-contrast MRI; no BPD n=28, mild BPD n=35 and moderate/severe BPD n=25) was complemented by cardiac function assessment (cine MRI).

Results: We identified abnormalities in PA flow and cardiac function, i.e. increased net forward volume right/left ratio, decreased mean relative area change and pathological right end-diastolic volume, to sensitively detect BPD-associated PVD while correcting for PMA (leave-one-out area under the curve 0.88, sensitivity 0.80 and specificity 0.81). We linked these changes to increased right ventricular (RV) afterload (RV-arterial coupling (p=0.02), PA mid-systolic notching (t2; p=0.015) and cardiac index (p=1.67×10^-8)) and correlated echocardiographic findings. Identified in moderate/severe BPD, we successfully applied the PA flow model in heterogeneous mild BPD cases, demonstrating strong correlation of PVD probability with indicators of BPD severity, i.e. duration of mechanical ventilation (r_s=0.63, p=2.20×10^-4) and oxygen supplementation (r_s=0.60, p=6.00×10^-4).

Conclusions: Abnormalities in MRI PA flow and cardiac function exhibit significant, synergistic potential to detect BPD-associated PVD, advancing the possibilities of risk-adapted monitoring.

FIGURE 1

Study design. Preterm infants <32 weeks postmenstrual age (PMA) with and without later development of bronchopulmonary dysplasia (BPD) were prospectively included in the AIRR (Attention to Infants at Respiratory Risks) study after informed parental consent. Comprehensive clinical monitoring included standard echocardiography. Magnetic resonance imaging (MRI) was performed at near-term age in unsedated infants spontaneously breathing room air. Pulmonary artery (PA) flow and cardiac function variables that characterise pulmonary vascular disease (PVD) in BPD were identified through interpreting imaging information in the context of clinical patient characterisation and pathophysiological knowledge on PVD development. Partially created with BioRender.com.

FIGURE 2

Altered pulmonary artery (PA) flow in the presence of increased right ventricular strain characterises infants with moderate/severe bronchopulmonary dysplasia (BPD) and their associated risk for pulmonary vascular disease (PVD). a) Leave-one-out area under the curve (AUC) for the PA flow model discriminating infants without BPD from infants with moderate/severe BPD. b, c) Calculated probability for PVD in mild BPD cases correlated positively with prolonged exposure to b) mechanical ventilation and c) oxygen (O₂). Spearman correlation coefficients and their p-values are shown.

FIGURE 3

Association of magnetic resonance imaging-detected lung vascular and cardiac function abnormalities to bronchopulmonary dysplasia (BPD) and BPD indicators. Individual pulmonary artery flow model parameters with a significant synergistic effect to discriminate between infants with and without BPD demonstrate increased net forward volume right/left ratio (NFV r/l) and right ventricular end-diastolic volume normalised to body surface area (RV EDV/BSA) in infants with a) moderate/severe BPD (NFV r/l: fold change (FC)=1.37, p=0.048; RV EDV/BSA: FC=1.35, p=0.0022) and with a history of prolonged exposure to days of b) oxygen (O₂) (NFV r/l: r=0.36, p=0.02; RV EDV/BSA: r=0.49, p=0.001) or c) mechanical ventilation (RV EDV/BSA: r=0.46, p=0.002) when compared with preterm infants without BPD. Although contributing to the model's performance, mean relative area change (RAC) is not significantly associated with moderate/severe BPD (FC=0.89, p=0.27), O₂ exposure (r= −0.14, p=0.39) or mechanical ventilation exposure (r= −0.21, p=0.19). No significant correlation was observed for mechanical ventilation (NFV r/l: r=0.25, p=0.11). p-values and correlation coefficients were calculated using Pearson's correlation.

FIGURE 4

Representative magnetic resonance imaging (MRI) images and flow curves. a) Representative phase-contrast flow MRI sequences of the right pulmonary artery (PA) with flow in different shades of grey coding direction of blood flow relative to the imaging plane. Semi-manual segmentation of the PA (red arrow) during PA flow measurement (Argus) allowed calculation of flow parameters such as net forward volume (NFV) and relative area change. b) Heart assessment in cine sequences including endocardial shapes and volumes of both right (purple) and left (red) ventricles after semi-manual annotation during systole and diastole. c, d) Representative time–flow curves derived from PA flow measurements: c) NFV over time in an infant without bronchopulmonary dysplasia (BPD) (postmenstrual age (PMA) 27.1 weeks; birthweight 920 g) and with severe BPD (PMA 24.0 weeks; birthweight 600 g), and d) flow (over the annotated range) over time in an infant without BPD (PMA 27.1 weeks; birthweight 920 g) and with severe BPD (PMA 26.3 weeks; birthweight 620 g).

FIGURE 5

Pathophysiological concept for lung vascular abnormalities in preterm infants with bronchopulmonary dysplasia (BPD). Maintained cardiac output through right ventricular (RV)–arterial coupling (stroke volume (SV)/end-systolic volume (ESV)) in the presence of compensated RV function facing a rarefied and/or remodelled lung vascular bed in established BPD resulted in significant changes to pulmonary artery (PA) flow and cardiac function parameters. The (pseudo-)increase in net forward volume right/left ratio (NFV r/l) together with the decrease in relative area change (RAC), indicating pre-dilation of the PA, and an increase in RV end-diastolic volume (EDV) normalised to body surface area in MRI, in line with echocardiographic RV enlargement and tricuspid valve insufficiency, indicated increased RV afterload resulting from the functional and structural impairment of the pulmonary vascular bed. EC: endothelial cell; SMC: smooth muscle cell. Partially created with Biorender.com.