Comparison of CT ventilation imaging and hyperpolarised gas MRI: effects of breathing manoeuvre.

Image registration of lung CT images acquired at different inflation levels has been proposed as a surrogate method to map lung 'ventilation'. Prior to clinical use, it is important to understand how this technique compares with direct ventilation imaging modalities such as hyperpolarised gas MRI. However, variations in lung inflation level have been shown to affect regional ventilation distributions. Therefore, the aim of this study was to evaluate the impact of lung inflation levels when comparing CT ventilation imaging to ventilation from 3He-MRI.
 
 7 asthma patients underwent breath-hold CT at total lung capacity (TLC) and functional residual capacity (FRC). 3He-MRI and a same-breath 1H-MRI were acquired at FRC+1L and TLC. Percentage ventilated volumes (%VVs) were calculated for FRC+1L and TLC 3He-MRI. TLC-CT and registered FRC-CT were used to compute a surrogate ventilation map from voxel-wise intensity differences in Hounsfield unit values, which was thresholded at the 10th and 20th percentiles. For direct comparison of CT and 3He-MRI ventilation, FRC+1L and TLC 3He-MRI were registered to TLC-CT indirectly via the corresponding same-breath 1H-MRI data. For 3He-MRI and CT ventilation comparison, Dice similarity coefficients (DSCs) between the binary segmentations were computed.
 
 The median (range) of %VVs for FRC+1L and TLC 3He-MRI were 90.5 (54.9-93.6) and 91.8 (67.8-96.2), respectively (p=0.018). For MRI versus CT ventilation comparison, statistically significant improvements in DSCs were observed for TLC 3He MRI when compared with FRC+1L, with median (range) values of 0.93 (0.86-0.93) and 0.86 (0.68-0.92), respectively (p=0.017), for the 10-100th percentile and 0.87 (0.83-0.88) and 0.81 (0.66-0.87), respectively (p=0.027), for the 20-100th percentile.
 
 Correlation of CT ventilation imaging and hyperpolarised gas MRI is sensitive to lung inflation level. For ventilation maps derived from CT acquired at FRC and TLC, a higher correlation with gas ventilation MRI can be achieved if the MRI is acquired at TLC. &#13

Patterns of regional lung physiology in cystic fibrosis using ventilation magnetic resonance imaging and multiple-breath washout

Hyperpolarised helium-3 (3He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution.32 children and adults with CF underwent MBW and 3He-MRI at a lung volume of end-inspiratory tidal volume (EIVT). In addition, 28 patients performed 3He-MRI at total lung capacity. 3He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection-diffusion-dependent ventilation heterogeneity (Sacin) were calculated.VDP and VHI at EIVT strongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV1) (r=-0.79 and r=-0.78, respectively). Two distinct 3He-MRI patterns were highlighted: patients with abnormal FEV1 had significantly (p<0.001) larger, but fewer, contiguous defects than those with normal FEV1, who tended to have numerous small volume defects. These two MRI patterns were delineated by a VDP of ∼10%. At total lung capacity, when compared to EIVT, VDP and VHI reduced in all subjects (p<0.001), demonstrating improved ventilation distribution and regions of volume-reversible and nonreversible ventilation abnormalities

Imaging biomarkers of lung ventilation in interstitial lung disease from ¹²⁹Xe and oxygen enhanced ¹H MRI

Purpose: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. Study type: Prospective longitudinal. Population: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. Field strength/sequence: MRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. Assessment: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. Statistical test: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. Results: The global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. Data conclusion: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF

A dual-channel deep learning approach for lung cavity estimation from hyperpolarized gas and proton MRI

Background Hyperpolarized gas MRI can quantify regional lung ventilation via biomarkers, including the ventilation defect percentage (VDP). VDP is computed from segmentations derived from spatially co-registered functional hyperpolarized gas and structural proton (1H)-MRI. Although acquired at similar lung inflation levels, they are frequently misaligned, requiring a lung cavity estimation (LCE). Recently, single-channel, mono-modal deep learning (DL)-based methods have shown promise for pulmonary image segmentation problems. Multichannel, multimodal approaches may outperform single-channel alternatives. Purpose We hypothesized that a DL-based dual-channel approach, leveraging both 1H-MRI and Xenon-129-MRI (129Xe-MRI), can generate LCEs more accurately than single-channel alternatives. Study Type Retrospective. Population A total of 480 corresponding 1H-MRI and 129Xe-MRI scans from 26 healthy participants (median age [range]: 11 [8–71]; 50% females) and 289 patients with pulmonary pathologies (median age [range]: 47 [6–83]; 51% females) were split into training (422 scans [88%]; 257 participants [82%]) and testing (58 scans [12%]; 58 participants [18%]) sets. Field Strength/Sequence 1.5-T, three-dimensional (3D) spoiled gradient-recalled 1H-MRI and 3D steady-state free-precession 129Xe-MRI. Assessment We developed a multimodal DL approach, integrating 129Xe-MRI and 1H-MRI, in a dual-channel convolutional neural network. We compared this approach to single-channel alternatives using manually edited LCEs as a benchmark. We further assessed a fully automatic DL-based framework to calculate VDPs and compared it to manually generated VDPs. Statistical Tests Friedman tests with post hoc Bonferroni correction for multiple comparisons compared single-channel and dual-channel DL approaches using Dice similarity coefficient (DSC), average boundary Hausdorff distance (average HD), and relative error (XOR) metrics. Bland–Altman analysis and paired t-tests compared manual and DL-generated VDPs. A P value < 0.05 was considered statistically significant. Results The dual-channel approach significantly outperformed single-channel approaches, achieving a median (range) DSC, average HD, and XOR of 0.967 (0.867–0.978), 1.68 mm (37.0–0.778), and 0.066 (0.246–0.045), respectively. DL-generated VDPs were statistically indistinguishable from manually generated VDPs (P = 0.710). Data Conclusion Our dual-channel approach generated LCEs, which could be integrated with ventilated lung segmentations to produce biomarkers such as the VDP without manual intervention. Evidence Level 4. Technical Efficacy Stage 1

Comparison of 3He and129Xe MRI for evaluation of lung microstructure and ventilation at 1.5T

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 < 0.001). VV% was larger for3He than129Xe (P = 0.001); average bias, 8.79%. A strong correlation between mean3He and129Xe ADC was obtained (r = 0.922, P < 0.001). MR parameters exhibited good correlations with pulmonary function tests. In COPD patients, mean CV of3He and129Xe VV% was 4.08% and 13.01%, respectively, with ICC coefficients of 0.541 (P = 0.061) and 0.458 (P = 0.095). Mean3He and129Xe ADC values were highly repeatable (mean CV: 2.98%, 2.77%, respectively; ICC: 0.995, P < 0.001; 0.936, P < 0.001). DATA CONCLUSION:129Xe lung MRI provides near-equivalent information to3He for quantitative lung ventilation and microstructural MRI at 1.5T. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage

Quantification of pulmonary perfusion in idiopathic pulmonary fibrosis with first pass dynamic contrast-enhanced perfusion MRI

Introduction Idiopathic pulmonary fibrosis (IPF) is a fatal disease of lung scarring. Many patients later develop raised pulmonary vascular pressures, sometimes disproportionate to the interstitial disease. Previous therapeutic approaches that have targeted pulmonary vascular changes have not demonstrated clinical efficacy, and quantitative assessment of regional pulmonary vascular involvement using perfusion imaging may provide a biomarker for further therapeutic insights. Methods We studied 23 participants with IPF, using dynamic contrast-enhanced MRI (DCE-MRI) and pulmonary function tests, including forced vital capacity (FVC), transfer factor (TLCO) and coefficient (KCO) of the lungs for carbon monoxide. DCE-MRI parametric maps were generated including the full width at half maximum (FWHM) of the bolus transit time through the lungs. Key metrics used were mean (FWHMmean) and heterogeneity (FWHMIQR). Nineteen participants returned at 6 months for repeat assessment. Results Spearman correlation coefficients were identified between TLCO and FWHMIQR (r=−0.46; p=0.026), KCO and FWHMmean (r=−0.42; p=0.047) and KCO and FWHMIQR (r=−0.51; p=0.013) at baseline. No statistically significant correlations were seen between FVC and DCE-MRI metrics. Follow-up at 6 months demonstrated statistically significant decline in FVC (p=0.040) and KCO (p=0.014), with an increase in FWHMmean (p=0.040), but no significant changes in TLCO (p=0.090) nor FWHMIQR (p=0.821). Conclusions DCE-MRI first pass perfusion demonstrates correlations with existing physiological gas exchange metrics, suggesting that capillary perfusion deficit (as well as impaired interstitial diffusion) may contribute to gas exchange limitation in IPF. FWHMmean showed a significant increase over a 6-month period and has potential as a quantitative biomarker of pulmonary vascular disease progression in IPF

PhysVENeT: a physiologically-informed deep learning-based framework for the synthesis of 3D hyperpolarized gas MRI ventilation

Functional lung imaging modalities such as hyperpolarized gas MRI ventilation enable visualization and quantification of regional lung ventilation; however, these techniques require specialized equipment and exogenous contrast, limiting clinical adoption. Physiologically-informed techniques to map proton (1H)-MRI ventilation have been proposed. These approaches have demonstrated moderate correlation with hyperpolarized gas MRI. Recently, deep learning (DL) has been used for image synthesis applications, including functional lung image synthesis. Here, we propose a 3D multi-channel convolutional neural network that employs physiologically-informed ventilation mapping and multi-inflation structural 1H-MRI to synthesize 3D ventilation surrogates (PhysVENeT). The dataset comprised paired inspiratory and expiratory 1H-MRI scans and corresponding hyperpolarized gas MRI scans from 170 participants with various pulmonary pathologies. We performed fivefold cross-validation on 150 of these participants and used 20 participants with a previously unseen pathology (post COVID-19) for external validation. Synthetic ventilation surrogates were evaluated using voxel-wise correlation and structural similarity metrics; the proposed PhysVENeT framework significantly outperformed conventional 1H-MRI ventilation mapping and other DL approaches which did not utilize structural imaging and ventilation mapping. PhysVENeT can accurately reflect ventilation defects and exhibits minimal overfitting on external validation data compared to DL approaches that do not integrate physiologically-informed mapping

MR properties of 19F C3F8 gas in the lungs of healthy volunteers: T2* and apparent diffusion coefficient at 1.5T and T2* at 3T

Purpose: To measure the transverse relaxation time (T2) and apparent diffusion co-efficient (ADC) of 19F-C3F8 gas in vivo in human lungs at 1.5T and 3T, and to de-termine the representative distribution of values of these parameters in a cohort of healthy volunteers. Methods: Mapping of ADC at lung inflation levels of functional residual capacity (FRC) and total lung capacity (TLC) was performed with inhaled 19F-C3F8 (eight subjects) and 129Xe (six subjects) at 1.5T. T2 mapping with 19F-C3F8 was performed at 1.5T (at FRC and TLC) for 8 subjects and at 3T (at TLC for seven subjects). Results: At both FRC and TLC, the 19F-C3F8 ADC was smaller than the free dif-fusion coefficient demonstrating airway microstructural diffusion restriction. From FRC to TLC, the mean ADC significantly increased from 1.56 mm2/s to 1.83 mm2/s (P = .0017) for 19F-C3F8, and from 2.49 mm2/s to 3.38 mm2/s (P = .0015) for 129Xe. The posterior-to-anterior gradient in ADC for FRC versus TLC in the superior half of the lungs was measured as 0.0308 mm2/s per cm versus 0.0168 mm2/s per cm for 19F-C3F8 and 0.0871 mm2/s per cm versus 0.0326 mm2/s per cm for 129Xe. A con-sistent distribution of 19F-C3F8 T2 values was observed in the lungs, with low values observed near the diaphragm and large pulmonary vessels. The mean T2 across vol-unteers was 4.48 ms at FRC and 5.33 ms at TLC for 1.5T, and 3.78 ms at TLC for 3T. Conclusion: In this feasibility study, values of physiologically relevant parameters of lung microstructure measurable by MRI (T2, and ADC) were established for C3F8 in vivo lung imaging in healthy volunteers

Age, sex, and lung volume dependence of dissolved xenon‐129 MRI gas exchange metrics

Purpose To characterize the dependence of Xe-MRI gas transfer metrics upon age, sex, and lung volume in a group of healthy volunteers. Methods Sixty-five subjects with no history of chronic lung disease were assessed with 129Xe-MRI using a four-echo 3D radial spectroscopic imaging sequence and a dose of xenon titrated according to subject height that was inhaled from a lung volume of functional residual capacity (FRC). Imaging was repeated in 34 subjects at total lung capacity (TLC). Regional maps of the fractions of dissolved xenon in red blood cells (RBC), membrane (M), and airspace (Gas) were acquired at an isotropic resolution of 2 cm, from which global averages of the ratios RBC:M, RBC:Gas, and M:Gas were computed. Results Data from 26 males and 36 females with a median age of 43 y (range: 20–69 y) were of sufficient quality to analyze. Age (p = 0.0006) and sex (p < 0.0001) were significant predictors for RBC:M, and a linear regression showed higher values and steeper decline in males: RBC:M(Males) = −0.00362 × Age + 0.60 (p = 0.01, R2 = 0.25); RBC:M(Females) = −0.00170 × Age + 0.44 (p = 0.02, R2 = 0.15). Similarly, age and sex were significant predictors for RBC:Gas but not for M:Gas. RBC:M, M:Gas and RBC:Gas were significantly lower at TLC than at FRC (plus inhaled volume), with an average 9%, 30% and 35% decrease, respectively. Conclusion Expected age and sex dependence of pulmonary function concurs with 129Xe RBC:M imaging results, demonstrating that these variables must be considered when reporting Xe-MRI metrics. Xenon doses and breathing maneuvers should be controlled due to the strong dependence of Xe-MRI metrics upon lung volume

Integrated cardiopulmonary MRI assessment of pulmonary hypertension

Pulmonary hypertension (PH) is a heterogeneous condition that can affect the lung parenchyma, pulmonary vasculature, and cardiac chambers. Accurate diagnosis often requires multiple complex assessments of the cardiac and pulmonary systems. MRI is able to comprehensively assess cardiac structure and function, as well as lung parenchymal, pulmonary vascular, and functional lung changes. Therefore, MRI has the potential to provide an integrated functional and structural assessment of the cardiopulmonary system in a single exam. Cardiac MRI is used in the assessment of PH in most large PH centers, whereas lung MRI is an emerging technique in patients with PH. This article reviews the current literature on cardiopulmonary MRI in PH, including cine MRI, black-blood imaging, late gadolinium enhancement, T1 mapping, myocardial strain analysis, contrast-enhanced perfusion imaging and contrast-enhanced MR angiography, and hyperpolarized gas functional lung imaging. This article also highlights recent developments in this field and areas of interest for future research including cardiac MRI-based diagnostic models, machine learning in cardiac MRI, oxygen-enhanced 1H imaging, contrast-free 1H perfusion and ventilation imaging, contrast-free angiography and UTE imaging