MRI Phenotyping of Severe BPD and Prediction of Outcomes

Cincinnati Childrens Hosp Med Ctr, Cincinnati OH

Investigators

Linked publications, trials & patents

Abstract

SUMMARY Bronchopulmonary Dysplasia (BPD) is a chronic cardiorespiratory disease of prematurity that is responsible for the majority of neonatal intensive care unit (NICU) admissions across the nation (approximately $13B/year in the US for the NICU alone). The disease has high mortality and morbidity, and results in lifelong cardiorespiratory illnesses that are sometimes diagnosed as asthma and COPD, which themselves comprise an even larger burden of disease. Survival among extremely premature infants has significantly improved since 1990, increasing the number of severe cases and the burden of disease. This disease burden disproportionately affects patients with severe disease, and that is the focus of this renewal proposal. There is a treatment gap that exists largely because of the paucity of sensitive endpoints for testing in infancy and the justifiable exclusion of the most severe patients from studies and trials. We have successfully developed free-breathing MRI methods that even in the most severe patients can safely quantify and define image-phenotypes of disease and predict respiratory outcomes. These methods have now been translated to clinical practice. We currently follow a cohort of 257 patients (N=216 severe), who are beginning to turn age 5 in 2024, and have demonstrated very strong relationships between neonatal MRI and short-and medium-term outcomes. The overall goal of this R01 renewal is to build on our prior work in neonatal MRI to precisely characterize sequelae of severe BPD in our existing cohort of patients at school age, evaluate tomographic progression of disease for the first time from NICU to childhood, create school-age outcomes-prediction models based on neonatal phenotype, and extend functional MRI (via hyperpolarized Xe and PREFUL) to neonates. In Aim 1 we will use our well-characterized MRI phenotypes and quantitative measures at infancy to predict respiratory morbidities at school age in the entire 257-patient cohort. In Aim 2 we will precisely measure tomographic disease progression from infancy to school age, with quantitative and objective measures of regional ventilation, alveolar simplification, gas exchange, airway abnormalities, and pulmonary vascular disease, via proton and hyperpolarized Xe MRI. Accurate functional measures remain challenging in the neonatal period, and this is the focus of Aim 3: to perform Xe and functional proton MRI in neonates with BPD. Preliminary data strongly support each of these Aims. Our previous R01 led to pioneering work that innovated new MRI techniques and significantly improved patient outcomes (increased survival, decreased tracheotomy, reduced respiratory readmissions); we will continue this translation and outcomes improvement via this renewal. By understanding progression of severe BPD with precision and accuracy, that knowledge can rapidly be translated into precision treatment of individual patients and improved outcomes at all ages.