PROJECT SUMMARY/ABSTRACT
Late-onset, non-infectious pulmonary complications following hematopoietic stem-cell transplant (HSCT) occur
in up to half of all patients, are heterogeneous in etiology and in clinical course, and are deadly. Spirometry is
the cornerstone of surveillance, yet half of the pediatric HSCT population are unable to perform spirometry. As
a result, post-HSCT lung injury in children often is diagnosed in an advanced stage, where therapeutic options
are limited, damage is irreversible, and mortality is high. Early detection of lung injury after HSCT is our best
opportunity to intervene, stabilize lung-function decline, and improve outcomes, and there is an urgent need for
better diagnostics for young HSCT patients—especially for those who are unable to perform spirometry. To this
end, we have developed inhaled hyperpolarized xenon-129 (129Xe) ventilation and gas-exchange magnetic
resonance imaging (MRI) techniques to spatially resolve, differentiate, and quantify small airway, interstitial, and
microvascular abnormalities. The long-term goal of this project is to lower pulmonary-related morbidity in the
pediatric HSCT population via the clinical application of 129Xe MRI as an imaging-based, lung-function
diagnostic. The central hypothesis of this proposal is that 129Xe MRI is feasible in very young children who are
unable to perform PFTs and will detect early lung involvement post-HSCT. Our approach is based on three
Specific Aims: (1) develop 129Xe gas-exchange MRI in children by imaging healthy-control volunteers and
patients with diagnosed gas-exchange impairment ages 6-18 years old; (2) phenotype post-HSCT pulmonary
involvement using 129Xe ventilation and gas-exchange MRI in children ages 6-18 years old who have received
HSCT, with longitudinal MRI and PFTs at ~100 days and 1-year post-HSCT; (3) optimize strategies for rapid
129Xe MRI in HSCT patients ages 2-5 years old. This approach is supported by our previous work and
experience showing 129Xe MRI is feasible in neonates, in young children who are unable to perform spirometry,
and in sedated patients. This approach is innovative because 129Xe gas-exchange MRI is novel to any pediatric
population, and imaging children with diagnosed gas-exchange impairment will build a conceptual bridge
between better-understood disease pathophysiology and 129Xe gas-exchange MRI findings, which will enhance
the clinical interpretation of 129Xe MRI and diagnosis of gas-exchange impairment in the HSCT population.
Preliminary data in pediatric HSCT patients revealed diffusion-barrier and RBC-transfer abnormalities,
suggesting a clinically-under-recognized, non-obstructive phenotype. This project will revolutionize clinical care
for young HSCT patients with pulmonary complications. Longitudinal trajectories of ventilation, interstitial, and
microvascular changes from 129Xe MRI post-HSCT will help in clinical risk stratification. 129Xe MRI will enable
surveillance and early detection in asymptomatic patients, phenotyping to personalize clinical management and
therapeutic approach, and robust assessment of lung function in very young children.
