129Xe and free-breathing 1H ventilation MRI in patients with cystic fibrosis: a dual-center study

Background Free-breathing 1H ventilation MRI shows promise but only single-center validation has yet been performed against methods which directly image lung ventilation in patients with cystic fibrosis (CF). Purpose To investigate the relationship between 129Xe and 1H ventilation images using data acquired at two centers. Study type Sequence comparison. Population Center 1; 24 patients with CF (12 female) aged 9–47 years. Center 2; 7 patients with CF (6 female) aged 13–18 years, and 6 healthy controls (6 female) aged 21–31 years. Data were acquired in different patients at each center. Field Strength/Sequence 1.5 T, 3D steady-state free precession and 2D spoiled gradient echo. Assessment Subjects were scanned with 129Xe ventilation and 1H free-breathing MRI and performed pulmonary function tests. Ventilation defect percent (VDP) was calculated using linear binning and images were visually assessed by H.M., L.J.S., and G.J.C. (10, 5, and 8 years' experience). Statistical Tests Correlations and linear regression analyses were performed between 129Xe VDP, 1H VDP, FEV1, and LCI. Bland–Altman analysis of 129Xe VDP and 1H VDP was carried out. Differences in metrics were assessed using one-way ANOVA or Kruskal–Wallis tests. Results 129Xe VDP and 1H VDP correlated strongly with; each other (r = 0.84), FEV1 z-score (129Xe VDP r = −0.83, 1H VDP r = −0.80), and LCI (129Xe VDP r = 0.91, 1H VDP r = 0.82). Bland–Altman analysis of 129Xe VDP and 1H VDP from both centers had a bias of 0.07% and limits of agreement of −16.1% and 16.2%. Linear regression relationships of VDP with FEV1 were not significantly different between 129Xe and 1H VDP (P = 0.08), while 129Xe VDP had a stronger relationship with LCI than 1H VDP. Data Conclusion 1H ventilation MRI shows large-scale agreement with 129Xe ventilation MRI in CF patients with established lung disease but may be less sensitive to subtle ventilation changes in patients with early-stage lung disease. Evidence Level 2 Technical Efficacy Stage

Comparison of MRI and VQ-SPECT as a screening test for patients with suspected CTEPH: CHANGE-MRI study design and rationale

The diagnostic strategy for chronic thromboembolic pulmonary hypertension (CTEPH) is composed of two components required for a diagnosis of CTEPH: the presence of chronic pulmonary embolism and an elevated pulmonary artery pressure. The current guidelines require that ventilation–perfusion single-photon emission computed tomography (VQ-SPECT) is used for the first step diagnosis of chronic pulmonary embolism. However, VQ-SPECT exposes patients to ionizing radiation in a radiation sensitive population. The prospective, multicenter, comparative phase III diagnostic trial CTEPH diagnosis Europe - MRI (CHANGE-MRI, ClinicalTrials.gov identifier NCT02791282) aims to demonstrate whether functional lung MRI can serve as an equal rights alternative to VQ-SPECT in a diagnostic strategy for patients with suspected CTEPH. Positive findings are verified with catheter pulmonary angiography or computed tomography pulmonary angiography (gold standard). For comparing the imaging methods, a co-primary endpoint is used. (i) the proportion of patients with positive MRI in the group of patients who have a positive SPECT and gold standard diagnosis for chronic pulmonary embolism and (ii) the proportion of patients with positive MRI in the group of patients with negative SPECT and gold standard. The CHANGE-MRI trial will also investigate the performance of functional lung MRI without i.v. contrast agent as an index test and identify cardiac, hemodynamic, and pulmonary MRI-derived parameters to estimate pulmonary artery pressures and predict 6–12 month survival. Ultimately, this study will provide the necessary evidence for the discussion about changes in the recommendations on the diagnostic approach to CTEPH

A dual center and dual vendor comparison study of automated perfusion‐weighted phase‐resolved functional lung magnetic resonance imaging with dynamic contrast‐enhanced magnetic resonance imaging in patients with cystic fibrosis

For sensitive diagnosis and monitoring of pulmonary disease, ionizing radiation-free imaging methods are of great importance. A noncontrast and free-breathing proton magnetic resonance imaging (MRI) technique for assessment of pulmonary perfusion is phase-resolved functional lung (PREFUL) MRI. Since there is no validation of PREFUL MRI across different centers and scanners, the purpose of this study was to compare perfusion-weighted PREFUL MRI with the well-established dynamic contrast-enhanced (DCE) MRI across two centers on scanners from two different vendors. Sixteen patients with cystic fibrosis (CF) (Center 1: 10 patients; Center 2: 6 patients) underwent PREFUL and DCE MRI at 1.5T in the same imaging session. Normalized perfusion-weighted values and perfusion defect percentage (QDP) values were calculated for the whole lung and three central slices (dorsal, central, ventral of the carina). Obtained parameters were compared using Pearson correlation, Spearman correlation, Bland–Altman analysis, Wilcoxon signed-rank test, and Wilcoxon rank-sum test. Moderate-to-strong correlations between normalized perfusion-weighted PREFUL and DCE values were found (posterior slice: r = 0.69, p  0.07). The feasibility of PREFUL MRI across two different centers and two different vendors was shown in patients with CF and obtained results were in agreement with DCE MRI

Multicenter standardization of phase-resolved functional lung MRI in patients with suspected chronic thromboembolic pulmonary hypertension

Background Detection of pulmonary perfusion defects is the recommended approach for diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This is currently achieved in a clinical setting using scintigraphy. Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is an alternative technique for evaluating regional ventilation and perfusion without the use of ionizing radiation or contrast media. Purpose To assess the feasibility and image quality of PREFUL-MRI in a multicenter setting in suspected CTEPH. Study Type This is a prospective cohort sub-study. Population Forty-five patients (64 ± 16 years old) with suspected CTEPH from nine study centers. Field Strength/Sequence 1.5 T and 3 T/2D spoiled gradient echo/bSSFP/T2 HASTE/3D MR angiography (TWIST). Assessment Lung signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between study centers with different MRI machines. The contrast between normally and poorly perfused lung areas was examined on PREFUL images. The perfusion defect percentage calculated using PREFUL-MRI (QDPPREFUL) was compared to QDP from the established dynamic contrast-enhanced MRI technique (QDPDCE). Furthermore, QDPPREFUL was compared between a patient subgroup with confirmed CTEPH or chronic thromboembolic disease (CTED) to other clinical subgroups. Statistical Tests t-Test, one-way analysis of variance (ANOVA), Pearson's correlation. Significance level was 5%. Results Significant differences in lung SNR and CNR were present between study centers. However, PREFUL perfusion images showed a significant contrast between normally and poorly perfused lung areas (mean delta of normalized perfusion −4.2% SD 3.3) with no differences between study sites (ANOVA: P = 0.065). QDPPREFUL was significantly correlated with QDPDCE (r = 0.66), and was significantly higher in 18 patients with confirmed CTEPH or CTED (57.9 ± 12.2%) compared to subgroups with other causes of PH or with excluded PH (in total 27 patients with mean ± SD QDPPREFUL = 33.9 ± 17.2%). Data Conclusion PREFUL-MRI could be considered as a non-invasive method for imaging regional lung perfusion in multicenter studies. Level of Evidence 3 Technical Efficacy Stage

Mapping of regional lung microstructural parameters using hyperpolarized 129Xe dissolved‐phase MRI in healthy volunteers and patients with chronic obstructive pulmonary disease

Purpose: To develop a novel technique for voxel‐based mapping of lung microstructural parameters using hyperpolarized 129Xe dissolved‐phase MR imaging during saturation recovery. Methods: A pulse sequence using a highly undersampled stack‐of‐stars trajectory was developed, and low‐rank plus sparse matrix decomposition was employed for reconstruction of regional 129Xe uptake dynamics into lung tissue. In 4 healthy volunteers and 9 patients with chronic obstructive pulmonary disease, the technique was tested and compared to chemical shift saturation recovery spectroscopy in patients. Reproducibility of 129Xe gas uptake imaging was assessed by computing coefficients of variation, and results were compared with other modalities. Results: Numerical simulations and results from in vivo measurements in patients with chronic obstructive pulmonary disease showed that septal wall thickness and surface‐to‐volume ratio can be measured with an accuracy close to spectroscopic measurements. The average of the microstructural parameters of the total lung volume showed good reproducibility (coefficient of variation wall thickness: 7.4% coefficient of variation surface‐to‐volume ratio: 7.5%) and correlated strongly with the findings of global chemical shift saturation recovery spectroscopy. Gravitational gradients of microstructural parameters and increased heterogeneity in chronic obstructive pulmonary disease patients were observed. Conclusion: A novel technique for mapping of regional lung microstructural parameters was introduced, and its feasibility was shown in healthy volunteers and chronic obstructive pulmonary disease patients

Comparison of phase-resolved functional lung (PREFUL) MRI derived perfusion and ventilation parameters at 1.5T and 3T in healthy volunteers

Purpose The purpose of this study is to evaluate the influence of different field strengths on perfusion and ventilation parameters, SNR and CNR derived by PREFUL MRI using predefined sequence parameters. Methods Data sets of free breathing 2d FLASH lung MRI were acquired from 15 healthy subjects at 1.5T and 3T (Magnetom Avanto and Skyra, Siemens Healthcare, Erlangen, Germany) with a maximum period of 3 days in between. The processed functional parameters regional ventilation (RVent), perfusion (Q), quantified perfusion (QQuant), perfusion defect percentage (QDP), ventilation defect percentage (VDP) and ventilation-perfusion match (VQM) were compared for systematic differences. Signal- and contrast-to-noise ratio (SNR and CNR) of both acquisitions were analyzed. Results RVent, Q, VDP, SNR and CNR presented no significant differences between 1.5T and 3T. QQuant (1.5T vs. 3T, P = 0.04), and QDP (1.5T vs. 3T, P>0.01) decreased significantly at 3T. Consequently, VQM increased significantly (1.5T vs. 3T, P>0.01). Skewness and kurtosis of the Q-values increased significantly at 3T (P>0.01). The mean Sørensen-Dice coefficients between both series were 0.91 for QDP and 0.94 for VDP. The Bland-Altman analysis of both series showed mean differences of 4.29% for QDP, 1.23% for VDP and -5.15% for VQM. Using the above-mentioned parameters for three-day repeatability at two different scanners and field strengths, the retrospective power calculation showed, that a sample size of 15 can detect differences of 3.7% for QDP, of 2.9% for VDP and differences of 2.6% for VQM. Conclusion Significant differences in QDP may be related to field inhomogeneities, which is expressed by increasing skewness and kurtosis at 3T. QQuant reveals only poor reproducibility between 1.5T and 3T. RVent, Q, VDP, SNR and CNR were not altered significantly at the used sequence parameters. Healthy participants with minimal defects present high spatial agreement of QDP and VDP

Regional investigation of lung function and microstructure parameters by localized 129Xe chemical shift saturation recovery and dissolved‐phase imaging: A reproducibility study

Purpose: To evaluate the reproducibility and regional variation of parameters obtained from localized 129Xe chemical shift saturation recovery (CSSR) MR spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to compare the results to 129Xe dissolved‐phase MR imaging. Methods: Thirteen healthy volunteers and 10 COPD patients were scanned twice using 129Xe dissolved‐phase imaging, CSSR, and ventilation imaging sequences. A 16‐channel phased‐array coil in combination with the regularized spectral localization achieved by sensitivity heterogeneity (SPLASH) method was used to perform a regional analysis of CSSR data. Lung function and microstructural parameters were obtained using Patz model functions and their reproducibility was assessed. Results: The Patz model alveolar wall thickness parameter shows good reproducibility on a regional basis with a median coefficient of variation of 6.5% in healthy volunteers and 12.4% in COPD patients. Significant regional differences of lung function parameters derived from localized CSSR were found in healthy volunteers and correlations with spirometric indices were found. Conclusion: Localized 129Xe CSSR provides reproducible estimates of alveolar wall thickness and is able to detect regional differences of lung microstructure