129Xe MRI in Pediatric Population With BPD

The most common respiratory complication of preterm birth, bronchopulmonary dysplasia (BPD), defined by a clinically assessed need for supplemental oxygen support at 36 weeks post-menstrual age, has actually increased in incidence as advancements in clinical respiratory care have improved initial survivability for very premature neonates. However, the burden of pulmonary disease continues beyond the NICU; the survivors are at greater risk for respiratory-related rehospitalization and diminished pulmonary capacity. Pulmonary imaging of the neonate has been limited to the clinical assessment of acute changes in respiratory status. The most widely accessible clinical imaging modalities, radiograph and computed tomography (CT), have significant limitations. Chest radiograph's sensitivity in the acute setting is limited because patients with significant respiratory dysfunction may exhibit only minor radiographic abnormalities, and although CT is considered the gold standard for clinical pulmonary imaging, it is not widely implemented because neonates may require sedation, especially for high-resolution CT, and are especially vulnerable to damage from ionizing radiation. Furthermore, CT is not appropriate for longitudinal assessment because of the link between serial radiation exposure and increased cancer risk.

As a nonionizing technique, magnetic resonance imaging (MRI) is an ideal modality for pulmonary imaging; in particular in the infant and pediatric population. Nevertheless, due to the low proton density of the lung parenchyma (only ~20% that of solid tissues), numerous air-tissue interfaces that lead to rapid signal decay, and cardiac and respiratory sources of motion that further degrade image quality, MRI has played a limited role in the evaluation of lung pathologies. Pulmonary MRI of the neonate is additionally confounded by small patient size and the delicate nature of transporting a NICU patient to the scanner. To overcome these limitations, the use of inhaled, hyperpolarized (HP) noble gases such as helium-3 (3He) and xenon-129 (129Xe) has come into play. Filling the air spaces within the lungs with either of these HP gases provides enough signal and contrast to obtain quality images on MRI.

There has been extensive work with HP 3He MRI in both the adult and pediatric population, but this gas is in extremely limited supply, making it increasingly expensive. 129Xe, on the other hand, is part of the atmosphere and as such does not suffer from supply constraints. Also, xenon dissolves in the lung tissue and blood, a process that is associated with characteristic shifts in the resonance frequency of 129Xe. As a result, the uptake and subsequent transport of 129Xe gas by the pulmonary circulation can be monitored, quantified and analyzed with regard to lung function at a temporal and spatial resolution that is infeasible with any other existing non-invasive modality.

In this study, the lung function in up to 30 infant subjects will be evaluated using HP 129Xe MRI. The subjects will be intubated and sedated neonates with known diagnosis of BPD. Although these subjects have lung disease and may be chronically intubated, they are stable clinically and not acutely ill decreasing the overall risk. When inhaled, 129Xe can be imaged within the lung parenchyma. Using a set of specialized MRI pulse sequences, the diffusion and gas-exchange properties of 129Xe in the lungs of these subjects will be evaluated. This will enable the investigators to determine the regional distribution of alveolar sizes, partial pressure of oxygen, alveolar wall thickness, and gas transport efficiency of the microvasculature within the lung. Each participant will be imaged once using HP 129Xe MRI along with the additional routine proton MRI sequences to further evaluate the structure, volume, and perfusion of the lung parenchyma.

The overall goal of this study is to develop improved quantitative imaging-based lung function parameters to evaluate BPD and determine the phenotypical variants of BPD using HP MRI. HP gas MRI offers additional information that cannot be obtained with CT, the current gold standard for imaging this disorder. Further, MRI offers the advantage of non-ionizing radiation, which is all the more important in the pediatric population particularly within this population who may getting repeat CT examinations throughout their lifetime. Although older children and adults may also benefit from this technology, the improved imaging and phenotyping of BPD will hopefully guide further treatment refinements of this complex disorder.