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.

Lung clearance index in detection of post-transplant bronchiolitis obliterans syndrome

“…We have also shown here that LCI is scalable and that it is elevated in those with pre-BOS, a putative early stage of OB that may be more reversible and amenable to future therapeutic intervention. These findings are supported by a recent study on ventilation magnetic resonance imaging (MRI) in paediatric stem-cell transplant patients, which showed evidence of ventilation defects even in those with normal spirometry [27]…”

In vivo methods and applications of xenon-129 magnetic resonance

“…2 ). Studies in children and young adults with CF [156] , [165] , [167] , lymphangioleiomyomatosis [168] and following allogenic haematopoietic stem cell transplantation [169] , where ventilation defects were detected in patients with clinically-normal spirometry (i.e. indicating that 129 Xe ventilation MRI is sensitive to “sub-clinical” disease), highlight the sensitivity of 129 Xe ventilation imaging to early-stage lung disease, which could allow earlier interventions to impede disease progression.…”

“…129 Xe lung MR is a versatile tool for the examination of lung function and structure, providing quantitative physiological information. Ventilation and diffusion MRI are well-established, repeatable techniques that are sensitive to early-stage lung disease [157] , [167] , [168] , [169] , [185] , [188] . They have the potential to detect lung abnormalities earlier than spirometry [168] , [169] and structural imaging [167] , [290] , allowing early intervention/therapy to mitigate further damage.…”

3D Magnetic Resonance Spirometry

“…In spontaneous breathing, standard spirometry loses all sensitivity to ventilation defects and any disease specificity as the global flow-volume loops are generally affected only when the lung is challenged to the limit of its abilities. Even at the high and low pressures that are reached during coached forced breathing, FVC and FEV 1 may fail revealing or staging lung dysfunction as it was brought to light early on by hyperpolarized gas MRI when the recorded percentage of ventilation defects did not always correlate with standard spirometry [20][21][22][23] . In 3D MR Spirometry, because of the long total scan time, only spontaneous breathing can be reasonably performed by the patient.…”