Pulmonary magnetic resonance imaging biomarkers of lung structure and function in adult survivors of bronchopulmonary dysplasia with COPD

Abstract

Bronchopulmonary dysplasia (BPD) is an emerging risk factor for chronic obstructive pulmonary disease. For BPD survivors, there are no guidelines for the management of lung disease that is often misdiagnosed as asthma. Pulmonary magnetic resonsance imaging (MRI) provides clinically-relevant lung biomarkers of ventilation abnormalities and emphysema. Here our objective was to quantify lung MRI biomarkers in adults with BPD to understand the underlying pathophysiologies responsible for their symptoms and abnormal pulmonary-function. We hypothesized that MRI measurements would be abnormal and reflect emphysema, not airways disease. Patients aged 20–29 year and born ≤32 weeks gestational age were included and those with MRI contraindications were excluded. A 25-year-old female never-smoker born <28 weeks gestation (S1) and a 27-year-old male ex-smoker born ~30 weeks gestation (S2) provided written-informed-consent and underwent pulmonary-function-tests and MRI. Lung abnormalities were quantified using ventilation defect percent (VDP), apparent diffusion coefficients (ADC) and mean linear intercept (Lm). Forced expiratory volume-in 1 sec (S1 = 46%_pred/S2 = 33%_pred), residual-volume (S1 = 192%_pred/S2 = 267%_pred) and diffusing-capacity-of-the-lung-for-carbon-monoxide (S1 = 73%_pred/S2 = 72%_pred) were abnormal. Chest–X-ray and computed tomography (CT) revealed mild structural abnormalities, while MRI VDP (S1 = 6%/S2 = 10%), ADC (S1 = 0.36 cm²/s/S2 = 0.37 cm²/s) and Lm (S1 = 400 μm/S2 = 430 μm) were markedly abnormal with ventilation defects spatially concordant with regions of low MRI signal-intensity and greater Lm, reflecting emphysema and/or gas-trapping. In BPD survivors, MRI biomarkers have the potential to serve as intermediate endpoints and help evaluate therapy.

Keywords:

• hyperpolarized noble gas MRI
• ultra-short echo time MRI
• bronchopulmonary dysplasia
• chronic lung disease

Public Interest Statement

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infants born extremely premature and is an emerging risk factor for chronic obstructive pulmonary disease (COPD). Adult survivors of premature birth have abnormally low lung function and are more likely to be prescribed asthma medication but unfortunately, there are no guidelines for their long-term follow-up. Pulmonary imaging methods have the potential to measure underlying lung pathophysiologies in these patients with the potential to guide therapy decisions. In this article, we describe the use of radiation-free pulmonary magnetic resonance imaging (MRI) methods to measure lung structure-function biomarkers in young adult survivors of bronchopulmonary dysplasia. We observed that such MRI-derived lung structure-function abnormalities were consistent with emphysema and chronic obstructive pulmonary disease. The development of radiation-free lung imaging measurements of COPD in survivors of BPD is especially important in young adults in whom lifelong treatment and monitoring is required.

Competing Interest

The authors declare no competing interests.

Acknowledgements

We thank L. Reid-Jones for clinical coordination and clinical database management. We thank D. Reese for MRI of research volunteers and are grateful Dr Rob Peters and Dr Michael Carl for their continued support of the development of pulmonary MRI pulse sequences.

Additional information

Notes on contributors

Khadija Sheikh

Our research is focused on developing a better understanding of lung structure and function in patients with COPD and asthma using imaging tools our lab discovered and developed including pulmonary functional magnetic resonance imaging. The research in this paper describes methods we have developed to better understand lung structure and functional and chronic obstructive pulmonary disease in young adult survivors of bronchopulmonary dysplasia. Such patients have abnormally low lung function in young adulthood and symptoms of airflow obstruction. This is important because it is not clear whether such respiratory abnormalities in preterm born adults reflect non-progressive lung disease stemming from lung structural abnormalities that occurred early in life or if there is ongoing and progressive lung disease that increase the risk of COPD.