Stabilization and Reversibility of Early Lung Abnormalities Post-HSCT Detected with Serial Hyperpolarized 129Xe MRI

Abstract

Introduction Early detection of lung abnormalities following hematopoietic stem cell transplant (HSCT) remains a challenge primarily due to the insensitivity of spirometry, the current clinical gold standard, to mild changes. This insensitivity carries through to assessing treatment response and personalizing pulmonary interventions for HSCT patients. Hyperpolarized 129Xe magnetic resonance imaging (MRI) has been demonstrated to be sensitive to early regional airway obstruction, and as a modality free of ionizing radiation, we hypothesized that serial 129Xe MRI could gauge treatment response in pediatric HSCT patients. Methods Four pediatric HSCT patients were recruited for serial 129Xe MRI. Xenon gas (86% 129Xe) was hyperpolarized to ∼20% using a commercial device (Polarean, Durham, NC). 129Xe ventilation images were acquired during a breath-hold (≤ 16 seconds) of up to 1 L Xe on a Philips 3T Achieva MR scanner. 129Xe ventilation defects, regions of relatively lower 129Xe MR signal due to airway obstruction, were quantified using a threshold of Results Figure 1 describes the cohort and clinical courses for each subject. Importantly, Subjects 1 & 2 were first imaged at approximately one-year post-HSCT and both had a diagnosis of multi-system GVHD including established lung involvement at the time of the first 129Xe MRI. Subjects 3 & 4 were imaged within the first year post-HSCT and had signs of early lung involvement. Figure 2 plots the trajectories of 129Xe VDP versus days post-HSCT for this cohort, and at the baseline, 129Xe VDP was elevated for all HSCT subjects (median 19.3%) relative to historical values for age-matched control subjects (∼5%). For the subjects with established lung involvement (1 & 2), stabilization of pulmonary function and 129Xe MRI was seen after extensive immunotherapy. For Subjects 3 and 4 with early lung involvement, improvements in 129Xe VDP were seen with relatively mild intervention of FAM therapy with and without steroids. Figure 3 demonstrates this reversibility of focal 129Xe ventilation deficits in Subject 4. Conclusions 129Xe MRI provides a sensitive means of quantifying early regional lung disease and treatment response following HSCT. These results suggest the potential reversibility of ventilation abnormalities and mild lung involvement with early detection and intervention, though larger studies are needed. 129Xe MRI may be repeated serially to individualize treatment strategies, such as the appropriate escalation or tapering of immunosuppression or to assess the effectiveness of new therapies. Furthermore, the spatial resolution of 129Xe MRI may be leveraged to target invasive procedures like bronchoscopy, where regions of persistent ventilation deficit could be identified and targeted for evaluation.