Xenon-129 MRI detects ventilation deficits in paediatric stem cell transplant patients unable to perform spirometry

Abstract

Background: Early detection of pulmonary morbidity following haematopoietic stem cell transplantation (HSCT) remains an important challenge for intervention, primarily due to the insensitivity of spirometry to early change, and in paediatrics, patient compliance provides additional challenges. Regional lung ventilation abnormalities in paediatric HSCT patients were quantified using hyperpolarised xenon-129 (129Xe) magnetic resonance imaging (MRI) and compared to spirometry.

Methods: Medically stable, paediatric allogeneic HSCT patients (n=23, ages 6-16 years) underwent an outpatient MRI scan where regional ventilation was quantified with a breath-hold of hyperpolarised 129Xe gas. Ventilation deficits, regions of the lung that ventilate poorly due to obstruction, were quantified as a ventilation defect percentage (VDP) and compared to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio, and forced expiratory flow at 25-75% of FVC (FEF25-75%) from spirometry using linear regression.

Results: The mean±sd 129Xe VDP was 10.5±9.4% (range 2.6-41.4%). 129Xe VDP correlated with FEV1, FEV1/FVC ratio and FEF25-75% (p≤0.02 for all comparisons). Ventilation deficits were detected in patients with normal spirometry (i.e. FEV1 >80%), supporting the sensitivity of 129Xe MRI to early obstruction reported in other pulmonary conditions. Seven (30%) patients could not perform spirometry, yet ventilation deficits were observed in five of these patients, detecting abnormalities that otherwise may have gone undetected and untreated until advanced.

Conclusion: Lung ventilation deficits were detected using hyperpolarised 129Xe gas MRI in asymptomatic paediatric HSCT patients and in a subgroup who were unable to perform reliable spirometry. 129Xe MRI provides a reliable imaging-based assessment of pulmonary involvement in this potentially difficult to diagnose paediatric population.

Conflict of interest statement

Conflict of interest: L.L. Walkup has nothing to disclose. Conflict of interest: K. Myers reports personal fees from Novartis and Bellicum, outside the submitted work. Conflict of interest: A. Nelson has nothing to disclose. Conflict of interest: M.M. Willmering has nothing to disclose. Conflict of interest: M. Grimley has nothing to disclose. Conflict of interest: S.M. Davies has nothing to disclose. Conflict of interest: C. Towe has nothing to disclose. Conflict of interest: J.C. Woods reports grants from and consultancy for Vertex Pharmaceuticals, and grants from Grifols, Inc., outside the submitted work.

Copyright ©ERS 2019.

Figures

FIGURE 1

Representative axial xenon-129 (129Xe) ventilation magnetic resonance images from four haematopoietic stem cell transplantation (HSCT) patients demonstrating the range of 129Xe ventilation patterns seen in this study. a) 15-year-old female, 145 days post-HSCT, forced expiratory volume in 1 s (FEV1) 108% predicted, 129Xe ventilation defect percentage (VDP) 3.0%; the subject has high FEV1 % pred, ventilation is homogenous and the 129Xe VDP is correspondingly low. The sensitivity of 129Xe MRI to mild lung abnormalities is demonstrated in the subjects in b) (15-year-old female, 3 years post-HSCT, FEV1 81% pred, 129Xe VDP 2.6%) and c) (13-year-old female, 93 days post-HSCT, FEV1 81% pred, 129Xe VDP 20%), both of whom have similar high FEV1 % pred, yet the subject in c) has large focal deficits (e.g. posterior left and right lungs near apexes, anterior right lung near the base) and higher VDP. d) 13-year-old female, 9 years post-HSCT, FEV1 52% pred, 129Xe VDP 41.4%. 129Xe ventilation is very heterogeneous with large deficits and correspondingly high 129Xe VDP and low FEV1 % pred.

FIGURE 2

Xenon-129 (129Xe) ventilation defect percentage (VDP) versus a) forced expiratory volume in 1 s (FEV1) % predicted; b) FEV1/forced vital capacity (FVC) ratio; c) forced expiratory flow at 25–75% of FVC (FEF25–75%). HSCT: haematopoietic stem cell transplantation.

FIGURE 3

a) Xenon-129 (129Xe) ventilation defect percentage (VDP) plotted against the number of days post-haematopoietic stem cell transplantation (HSCT); b) subjects imaged within the first year (dashed box in a)) FEV1: forced expiratory volume in 1 s; PFT: pulmonary function test.