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Rationale: Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood. Objectives: We assessed the differential associations between the historical diagnosis of bronchopulmonary dysplasia (BPD) and current lung function phenotypes on lung ventilation and microstructure in preterm-born children using hyperpolarised 129Xe ventilation and diffusion-weighted MRI, and multiple breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 years) including 44 born preterm (≤34 weeks’ gestation) and 19 term-born controls (≥37 weeks’ gestation). Preterm-born children were classified, using spirometry, into prematurity-associated obstructive lung disease (POLD, FEV1

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique – hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe – a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.

Purpose\ud \ud This work assesses the accuracy of the stretched exponential (SEM) and cylinder models of lung microstructural length scales that can be derived from hyperpolarized gas DWI. This was achieved by simulating 3He and 129Xe DWI signals within two micro‐CT–derived realistic acinar airspace meshes that represent healthy and idiopathic pulmonary fibrosis lungs.\ud \ud \ud Methods\ud \ud The healthy and idiopathic pulmonary fibrosis acinar airway meshes were derived from segmentations of 3D micro‐CT images of excised human lungs and meshed for finite element simulations of the Bloch‐Torrey equations. 3He and 129Xe multiple b value DWI experiments across a range of diffusion times (3He Δ = 1.6 ms; 129Xe Δ = 5 to 20 ms) were simulated in each mesh. Global SEM mean diffusive length scale and cylinder model mean chord length value was derived from each finite element simulation and compared against each mesh’s mean linear intercept length, calculated from intercept length measurements within micro‐CT segmentation masks.\ud \ud \ud Results\ud \ud The SEM‐derived mean diffusive length scale was within ±10% of the mean linear intercept length for simulations with both 3He (Δ = 1.6 ms) and 129Xe (Δ = 7 to 13 ms) in the healthy mesh, and with 129Xe (Δ = 13 to 20 ms) for the idiopathic pulmonary fibrosis mesh, whereas for the cylinder model–derived mean chord length the closest agreement with mean linear intercept length (11.7% and 22.6% difference) was at 129Xe Δ = 20 ms for both healthy and IPF meshes, respectively.\ud \ud \ud Conclusion\ud \ud This work validates the use of the SEM for accurate estimation of acinar dimensions and indicates that the SEM is relatively robust across a range of experimental conditions and acinar length scales.

Enlargements of distal airspaces can indicate pathological changes in the lung, but accessible and precise techniques able to measure these regions are lacking. Airspace Dimension Assessment with inhaled nanoparticles (AiDA) is a new method developed for in vivo measurement of distal airspace dimensions. The aim of this study was to benchmark the AiDA method against quantitative measurements of distal airspaces from hyperpolarised 129Xe diffusion-weighted (DW)-lung magnetic resonance imaging (MRI). AiDA and 129Xe DW-MRI measurements were performed in 23 healthy volunteers who spanned an age range of 23–70 years. The relationship between the 129Xe DW-MRI and AiDA metrics was tested using Spearman’s rank correlation coefficient. Significant correlations were observed between AiDA distal airspace radius (rAiDA) and mean 129Xe apparent diffusion coefficient (ADC) (p

Purpose\ud To develop and assess a method for acquiring coregistered proton anatomical and hyperpolarized 129Xe ventilation MR images of the lungs with compressed sensing (CS) in a single breath hold.\ud \ud Methods\ud Retrospective CS simulations were performed on fully sampled ventilation images acquired from one healthy smoker to optimize reconstruction parameters. Prospective same‐breath anatomical and ventilation images were also acquired in five ex‐smokers with an acceleration factor of 3 for hyperpolarized 129Xe images, and were compared to fully sampled images acquired during the same session. The following metrics were used to assess data fidelity: mean absolute error (MAE), root mean square error, and linear regression of the signal intensity between fully sampled and undersampled images. The effect of CS reconstruction on two quantitative imaging metrics routinely reported [percentage ventilated volume (%VV) and heterogeneity score] was also investigated.\ud \ud Results\ud Retrospective simulations showed good agreement between fully sampled and CS‐reconstructed (acceleration factor of 3) images with MAE (root mean square error) of 3.9% (4.5%). The prospective same‐breath images showed a good match in ventilation distribution with an average R2 of 0.76 from signal intensity linear regression and a negligible systematic bias of +0.1% in %VV calculation. A bias of −1.8% in the heterogeneity score was obtained.\ud \ud Conclusion\ud With CS, high‐quality 3D images of hyperpolarized 129Xe ventilation (resolution 4.2 × 4.2 × 7.5 mm3) can be acquired with coregistered 1H anatomical MRI in a 15‐s breath hold. The accelerated acquisition time dispenses with the need for registration between separate breath‐hold 129Xe and 1H MRI, enabling more accurate %VV calculation.

Prognosticating idiopathic pulmonary fibrosis (IPF) is challenging, in part due to a lack of sensitive biomarkers. A recent article in Thorax described how hyperpolarised xenon magnetic resonance spectroscopy may quantify regional gas exchange in IPF lungs. In a population of patients with IPF, we find that the xenon signal from red blood cells diminishes relative to the tissue/plasma signal over a 12-month time period, even when the diffusion factor for carbon monoxide is static over the same time period. We conclude that hyperpolarised 129Xe MR spectroscopy may be sensitive to short-term changes in interstitial gas diffusion in IPF.

Background\ud MRI with inhaled hyperpolarized helium 3 (3He) allows for functional and structural imaging of the lungs. Hyperpolarized gas diffusion-weighted (DW) MRI provides noninvasive and quantitative assessment of microstructural acinar changes in the lungs.\ud \ud Purpose\ud To investigate whether microstructural imaging metrics from in-vivo hyperpolarized 3He DW MRI are sensitive to longitudinal changes in a cohort of participants with idiopathic pulmonary fibrosis (IPF) and to evaluate the reproducibility of these metrics and their correlation with existing clinical measures of IPF disease severity.\ud \ud Materials and Methods\ud In this prospective study, 18 participants with IPF underwent 3He DW MRI at 1.5 T and 11 participants underwent an identical same-day examination for reproducibility assessment. Thirteen participants returned for 6- and 12-month follow-up examinations. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide and forced vital capacity, were performed at each examination. The apparent diffusion coefficient (ADC) and stretched exponential model–derived mean diffusive length scale (LmD) from DW MRI was compared with baseline CT fibrosis scores and pulmonary function tests by using Spearman rank correlation coefficient. Longitudinal changes in DW MRI and pulmonary function test measurements were assessed with Friedman tests and post hoc Dunn test.\ud \ud Results\ud 3He ADC and LmD were reproducible (mean Bland-Altman analysis bias, 0.002 cm2 · sec-1 and −1.5 μm, respectively). Elevated ADC and LmD regions qualitatively corresponded to fibrotic regions at CT. ADC and LmD correlated with diffusing capacity of the lungs for carbon monoxide (respectively: r = −0.56, P = .017; and r = −0.54, P = .02) and CT fibrosis score (respectively: r = 0.71, P = .001; and r = 0.65, P = .003). LmD increased by 12 μm after 12 months (P = .001) whereas mean ADC (P = .17), forced vital capacity (P = .12), and diffusing capacity of the lungs for carbon monoxide (P > .99) were not statistically different between examinations.\ud \ud Conclusion\ud Helium 3 diffusion-weighted MRI-derived mean diffusive length scale demonstrates longitudinal changes in lungs affected by idiopathic pulmonary fibrosis.

In this study, the effect of lung volume on quantitative measures of lung ventilation was investigated using MRI with hyperpolarized 3He and 129Xe. Six volunteers were imaged with hyperpolarized 3He at five different lung volumes (residual volume (RV), RV+1L, functional residual capacity (FRC), FRC+1L and total lung capacity (TLC)), and three were also imaged with hyperpolarized 129Xe. Imaging at each of the lung volumes was repeated twice on the same day with corresponding 1H lung anatomical images. Percentage lung ventilated volume (%VV) and variation of signal intensity (heterogeneity score, Hscore) were evaluated. Increased ventilation heterogeneity, quantified by reduced %VV and increased Hscore, was observed at lower lung volumes with the least ventilation heterogeneity observed at TLC. For 3He MRI data, the coefficient of variation of %VV was less than 1.5% and less than 5.5% for Hscore at all lung volumes, whilst for 129Xe data the values were 4% and 10% respectively. Generally, %VV generated from 129Xe images was lower than that seen from 3He images. The good repeatability of 3He %VV found here supports prior publications showing that percentage lung ventilated volume is a robust method for assessing global lung ventilation. The greater ventilation heterogeneity observed at lower lung volumes indicates that there may be partial airway closure in healthy lungs and that lung volume should be carefully considered for reliable longitudinal measurements of %VV and Hscore. The results suggest that imaging patients at different lung volumes may help to elucidate obstructive disease pathophysiology and progression.

BACKGROUND: To support translational lung MRI research with hyperpolarized129Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from3He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of129Xe functional metrics have not been reported. PURPOSE/HYPOTHESIS: To compare hyperpolarized129Xe and3He MRI-derived quantitative metrics of lung ventilation and microstructure, and their repeatability, at 1.5T. STUDY TYPE: Retrospective. POPULATION: Fourteen healthy nonsmokers (HN), five exsmokers (ES), five patients with chronic obstructive pulmonary disease (COPD), and 16 patients with nonsmall-cell lung cancer (NSCLC). FIELD STRENGTH/SEQUENCE: 1.5T. NSCLC, COPD patients and selected HN subjects underwent 3D balanced steady-state free-precession lung ventilation MRI using both3He and129Xe. Selected HN, all ES, and COPD patients underwent 2D multislice spoiled gradient-echo diffusion-weighted lung MRI using both hyperpolarized gas nuclei. ASSESSMENT: Ventilated volume percentages (VV%) and mean apparent diffusion coefficients (ADC) were derived from imaging. COPD patients performed the whole MR protocol in four separate scan sessions to assess repeatability. Same-day pulmonary function tests were performed. STATISTICAL TESTS: Intermetric correlations: Spearman's coefficient. Intergroup/internuclei differences: analysis of variance / Wilcoxon's signed rank. Repeatability: coefficient of variation (CV), intraclass correlation (ICC) coefficient. RESULTS: A significant positive correlation between3He and129Xe VV% was observed (r = 0.860, P

PURPOSE: To obtain whole lung morphometry measurements from (129) Xe in a single breath-hold with 3D multiple b-value (129) Xe diffusion-weighted MRI (DW-MRI) with an empirically optimized diffusion time and compressed sensing for scan acceleration. METHODS: Prospective three-fold undersampled 3D multiple b-value hyperpolarized (129) Xe DW-MRI datasets were acquired, and the diffusion time (Δ) was iterated so as to provide diffusive length scale (LmD ) estimates from the stretched exponential model (SEM) that are comparable to those from (3) He. The empirically optimized (129) Xe diffusion time was then implemented with a four-fold undersampling scheme and was prospectively benchmarked against (3) He measurements in a cohort of five healthy volunteers, six ex-smokers, and two chronic obstructive pulmonary disease patients using both SEM-derived LmD and cylinder model (CM)-derived mean chord length (Lm). RESULTS: Good agreement between the mean (129) Xe and (3) He LmD (mean difference, 2.2%) and Lm (mean difference, 1.1%) values was obtained in all subjects at an empirically optimized (129) Xe Δ = 8.5 ms. CONCLUSION: Compressed sensing has facilitated single-breath 3D multiple b-value (129) Xe DW-MRI acquisitions, and results at (129) Xe Δ = 8.5 ms indicate that (129) Xe provides a viable alternative to (3) He for whole lung morphometry mapping with either the SEM or CM. Magn Reson Med, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.