Initial feasibility and challenges of hyperpolarized 129Xe MRI in neonates with bronchopulmonary dysplasia

Purpose The underlying functional and microstructural lung disease in neonates who are born preterm (bronchopulmonary dysplasia, BPD) remains poorly characterized. Moreover, there is a lack of suitable techniques to reliably assess lung function in this population. Here, we report our preliminary experience with hyperpolarized 129Xe MRI in neonates with BPD. Methods Neonatal intensive care patients with established BPD were recruited (N = 9) and imaged at a corrected gestational age of median:40.7 (range:37.1, 44.4) wk using a 1.5T neonatal scanner. 2D 129Xe ventilation and diffusion-weighted images and dissolved phase spectroscopy were acquired, alongside 1H 3D radial UTE. 129Xe images were acquired during a series of short apneic breath-holds (˜3 s). 1H UTE images were acquired during tidal breathing. Ventilation defects were manually identified and qualitatively compared to lung structures on UTE. ADCs were calculated on a voxel-wise basis. The signal ratio of the 129Xe red blood cell (RBC) and tissue membrane (M) resonances from spectroscopy was determined. Results Spiral-based 129Xe ventilation imaging showed good image quality and sufficient sensitivity to detect mild ventilation abnormalities in patients with BPD. 129Xe ADC values were elevated above that expected given healthy data in older children and adults (median:0.046 [range:0.041, 0.064] cm2s−1); the highest value obtained from an extremely pre-term patient. 129Xe spectroscopy revealed a low RBC/M ratio (0.14 [0.06, 0.21]). Conclusion We have demonstrated initial feasibility of 129Xe lung MRI in neonates. With further data, the technique may help guide management of infant lung diseases in the neonatal period and beyond

Human upper-airway respiratory airflow: In vivo comparison of computational fluid dynamics simulations and hyperpolarized 129Xe phase contrast MRI velocimetry

Computational fluid dynamics (CFD) simulations of respiratory airflow have the potential to change the clinical assessment of regional airway function in health and disease, in pulmonary medicine and otolaryngology. For example, in diseases where multiple sites of airway obstruction occur, such as obstructive sleep apnea (OSA), CFD simulations can identify which sites of obstruction contribute most to airway resistance and may therefore be candidate sites for airway surgery. The main barrier to clinical uptake of respiratory CFD to date has been the difficulty in validating CFD results against a clinical gold standard. Invasive instrumentation of the upper airway to measure respiratory airflow velocity or pressure can disrupt the airflow and alter the subject’s natural breathing patterns. Therefore, in this study, we instead propose phase contrast (PC) velocimetry magnetic resonance imaging (MRI) of inhaled hyperpolarized 129Xe gas as a non-invasive reference to which airflow velocities calculated via CFD can be compared. To that end, we performed subject-specific CFD simulations in airway models derived from 1H MRI, and using respiratory flowrate measurements acquired synchronously with MRI. Airflow velocity vectors calculated by CFD simulations were then qualitatively and quantitatively compared to velocity maps derived from PC velocimetry MRI of inhaled hyperpolarized 129Xe gas. The results show both techniques produce similar spatial distributions of high velocity regions in the anterior-posterior and foot-head directions, indicating good qualitative agreement. Statistically significant correlations and low Bland-Altman bias between the local velocity values produced by the two techniques indicates quantitative agreement. This preliminary in vivo comparison of respiratory airway CFD and PC MRI of hyperpolarized 129Xe gas demonstrates the feasibility of PC MRI as a technique to validate respiratory CFD and forms the basis for further comprehensive validation studies. This study is therefore a first step in the pathway towards clinical adoption of respiratory CFD

Protocols for multi-site trials using hyperpolarized 129Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the 129Xe MRI clinical trials consortium

Hyperpolarized (HP) 129Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129Xe MRI. Recommendations are described for the most common HP gas MRI techniques—calibration, ventilation, alveolar-airspace size, and gas exchange—across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129Xe MRI for multi-site pulmonary research