Airway microstructure in idiopathic pulmonary fibrosis: assessment at hyperpolarized 3He diffusion-weighted MRI

Background 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. Purpose 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. Materials and Methods 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. Results 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. Conclusion Helium 3 diffusion-weighted MRI-derived mean diffusive length scale demonstrates longitudinal changes in lungs affected by idiopathic pulmonary fibrosis

Detection of early sub-clinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarized gas MRI

Hyperpolarised 3He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6–16 years) with clinically stable mild cystic fibrosis (CF) (FEV1>−1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure–function relationships

Assessment of the influence of lung inflation state on the quantitative parameters derived from hyperpolarized gas lung ventilation MRI in healthy volunteers.

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

Implementable Deep Learning for Multi-sequence Proton MRI Lung Segmentation:A Multi-center, Multi-vendor, and Multi-disease Study

Background: Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton (1H)-MRI lung segmentation. However, previous deep learning studies have utilized single-center data and limited acquisition parameters.Purpose: Develop a generalizable CNN for lung segmentation in 1H-MRI, robust to pathology, acquisition protocol, vendor, and center.Study type: Retrospective.Population: A total of 809 1H-MRI scans from 258 participants with various pulmonary pathologies (median age (range): 57 (6–85); 42% females) and 31 healthy participants (median age (range): 34 (23–76); 34% females) that were split into training (593 scans (74%); 157 participants (55%)), testing (50 scans (6%); 50 participants (17%)) and external validation (164 scans (20%); 82 participants (28%)) sets.Field Strength/Sequence: 1.5-T and 3-T/3D spoiled-gradient recalled and ultrashort echo-time 1H-MRI.Assessment: 2D and 3D CNNs, trained on single-center, multi-sequence data, and the conventional spatial fuzzy c-means (SFCM) method were compared to manually delineated expert segmentations. Each method was validated on external data originating from several centers. Dice similarity coefficient (DSC), average boundary Hausdorff distance (Average HD), and relative error (XOR) metrics to assess segmentation performance.Statistical Tests: Kruskal–Wallis tests assessed significances of differences between acquisitions in the testing set. Friedman tests with post hoc multiple comparisons assessed differences between the 2D CNN, 3D CNN, and SFCM. Bland–Altman analyses assessed agreement with manually derived lung volumes. A P value of &lt;0.05 was considered statistically significant.Results: The 3D CNN significantly outperformed its 2D analog and SFCM, yielding a median (range) DSC of 0.961 (0.880–0.987), Average HD of 1.63 mm (0.65–5.45) and XOR of 0.079 (0.025–0.240) on the testing set and a DSC of 0.973 (0.866–0.987), Average HD of 1.11 mm (0.47–8.13) and XOR of 0.054 (0.026–0.255) on external validation data.Data Conclusion: The 3D CNN generated accurate 1H-MRI lung segmentations on a heterogenous dataset, demonstrating robustness to disease pathology, sequence, vendor, and center.Evidence Level: 4.Technical Efficacy: Stage 1.</p

Supine posture changes lung volumes and increases ventilation heterogeneity in cystic fibrosis

INTRODUCTION: Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. METHODS: 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. RESULTS: From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01). LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude of change with posture for both LCIalv and FRCalv in both groups, with a greater effect of change in lung volume in HC compared with children with CF. The % change in LCIalv for all subjects correlated significantly with lung volume % changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r = 0.54,p<0.001)). CONCLUSION: There is a significant increase in LCI from sitting to supine, which we believe to be in part due to changes in lung volume and also increasing ventilation heterogeneity related to posture. This may have implications in longitudinal measurements from infancy to older childhood and for studies comparing supine imaging methods to LCI

Model-based Bayesian inference of the ventilation distribution in patients with Cystic Fibrosis from multiple breath washout, with comparison to ventilation MRI

Background Indices of ventilation heterogeneity (VH) from multiple breath washout (MBW) have been shown to correlate well with VH indices derived from hyperpolarised gas ventilation MRI. Here we report the prediction of ventilation distributions from MBW data using a mathematical model, and the comparison of these predictions with imaging data. Methods We developed computer simulations of the ventilation distribution in the lungs to model MBW measurement with 3 parameters: determining the extent of VH; , the lung volume; and , the dead-space volume. These were inferred for each individual from supine MBW data recorded from 25 patients with cystic fibrosis (CF) using approximate Bayesian computation. The fitted models were used to predict the distribution of gas imaged by 3He ventilation MRI measurements collected from the same visit. Results The MRI indices measured (, the fraction of pixels below one-third of the mean intensity and , the coefficient of variation of pixel intensity) correlated strongly with those predicted by the MBW model fits ( respectively). There was also good agreement between predicted and measured MRI indices (mean bias limits of agreement: and Fitted model parameters were robust to truncation of MBW data. Conclusion We have shown that the ventilation distribution in the lung can be inferred from an MBW signal, and verified this using ventilation MRI. The Bayesian method employed extracts this information with fewer breath cycles than required for LCI, reducing acquisition time required, and gives uncertainty bounds, which are important for clinical decision making

Observation of cardiogenic flow oscillations in healthy subjects with hyperpolarized He-3 MRI

Recently, dynamic MRI of hyperpolarized 3He during inhalation revealed an alternation of the image intensity between left and right lungs with a cardiac origin (Sun Y, Butler JP, Ferrigno M, Albert MS, Loring SH. Respir Physiol Neurobiol 185: 468–471, 2013). This effect is investigated further using dynamic and phase-contrast flow MRI with inhaled 3He during slow inhalations (flow rate ∼100 ml/s) to elucidate airflow dynamics in the main lobes in six healthy subjects. The ventilation MR signal and gas inflow in the left lower lobe (LLL) of the lungs were found to oscillate clearly at the cardiac frequency in all subjects, whereas the MR signals in the other parts of the lungs had a similar oscillatory behavior but were smaller in magnitude and in anti-phase to the signal in the left lower lung. The airflow in the main bronchi showed periodic oscillations at the frequency of the cardiac cycle. In four of the subjects, backflows were observed for a short period of time of the cardiac cycle, demonstrating a pendelluft effect at the carina bifurcation between the left and right lungs. Additional 1H structural MR images of the lung volume and synchronized ECG recording revealed that maximum inspiratory flow rates in the LLL of the lungs occurred during systole when the corresponding left lung volume increased, whereas the opposite effect was observed during diastole, with gas flow redirected to the other parts of the lung. In conclusion, cardiogenic flow oscillations have a significant effect on regional gas flow and distribution within the lungs

Reproducibility of Quantitative Indices of Lung Function and Microstructure from 129Xe Chemical Shift Saturation Recovery (CSSR) MR Spectroscopy

Purpose: To evaluate the reproducibility of indices of lung microstructure and function derived from 129Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). To study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level. Methods: Preliminary data was collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, nine age-matched volunteers were scanned three times on one day, and five COPD patients were scanned on three separate days to assess short and long-term reproducibility. Results: CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P<0.001; P=0.057, respectively). Intra-subject standard deviations of ST were lower than previously-measured differences between volunteers and subjects with interstitial lung disease. Coefficient of variation (CV) values of ST were 4.3±1.9% and 6.0±4.3% in volunteers and COPD patients, respectively, which are comparable to CV values for whole-lung diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1±8.1% and 17.8±19.5%, respectively. Conclusion: 129Xe CSSR presents a reproducible method for estimation of alveolar septal thickness