129 Xe and Free-Breathing 1 H Ventilation MRI in Patients With Cystic Fibrosis: A Dual-Center Study.

BACKGROUND: Free-breathing 1 H 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 129 Xe and 1 H 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 129 Xe ventilation and 1 H 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 129 Xe VDP, 1 H VDP, FEV1 , and LCI. Bland-Altman analysis of 129 Xe VDP and 1 H VDP was carried out. Differences in metrics were assessed using one-way ANOVA or Kruskal-Wallis tests. RESULTS: 129 Xe VDP and 1 H VDP correlated strongly with; each other (r = 0.84), FEV1 z-score (129 Xe VDP r = -0.83, 1 H VDP r = -0.80), and LCI (129 Xe VDP r = 0.91, 1 H VDP r = 0.82). Bland-Altman analysis of 129 Xe VDP and 1 H 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 129 Xe and 1 H VDP (P = 0.08), while 129 Xe VDP had a stronger relationship with LCI than 1 H VDP. DATA CONCLUSION: 1 H ventilation MRI shows large-scale agreement with 129 Xe 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 2.

Volume-Controlled 19 F MR Ventilation Imaging of Fluorinated Gas.

BACKGROUND: 19 F MRI of inhaled gas tracers has developed into a promising tool for pulmonary diagnostics. Prior to clinical use, the intersession repeatability of acquired ventilation parameters must be quantified and maximized. PURPOSE: To evaluate repeatability of static and dynamic 19 F ventilation parameters and correlation with predicted forced expiratory volume in 1 second (FEV1 %pred) with and without inspiratory volume control. STUDY TYPE: Prospective. POPULATION: A total of 30 healthy subjects and 26 patients with chronic obstructive pulmonary disease (COPD). FIELD STRENGTH/SEQUENCE: Three-dimensional (3D) gradient echo pulse sequence with golden-angle stack-of-stars k-space encoding at 1.5 T. ASSESSMENT: All study participants underwent 19 F ventilation MRI over eight breaths with inspiratory volume control (w VC) and without inspiratory volume control (w/o VC), which was repeated within 1 week. Ventilated volume percentage (VVP), fractional ventilation (FV), and wash-in time (WI) were computed. Lung function testing was conducted on the first visit. STATISTICAL TESTS: Correlation between imaging and FEV1 %pred was measured using Pearson correlation coefficient (r). Differences in imaging parameters between first and second visit were analyzed using paired t-test. Repeatability was quantified using intraclass correlation coefficient (ICC) and coefficient of variation (CoV). Minimum detectable effect size (MDES) was calculated with a power analysis for study size n = 30 and a power of 0.8. All hypotheses were tested with a significance level of 5% two sided. RESULTS: Strong and moderate linear correlations with FEV1 %pred for COPD patients were found in almost all imaging parameters. The ICC w VC exceeds the ICC w/o VC for all imaging parameters. CoV was significantly lower w VC for initial VVP in COPD patients, FV, CoV FV, WI and standard deviation (SD) of WI. MDES of all imaging parameters were smaller w VC. DATA CONCLUSION: 19 F gas wash-in MRI with inspiratory volume control increases the correlation and repeatability of imaging parameters with lung function testing. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Absolute thermometry using hyperpolarized 129 Xe free-induction decay and spin-echo chemical-shift imaging in rats.

PURPOSE: To implement and test variants of chemical shift imaging (CSI) acquiring both free induction decays (FIDs) showing all dissolved-phase compartments and spin echoes for specifically assessing 129 $$ {}^{129} $$ Xe in lipids in order to perform precise lipid-dissolved 129 $$ {}^{129} $$ Xe MR thermometry in a rat model of general hypothermia. METHODS: Imaging was performed at 2.89 T. T 2 $$ {T}_2 $$ of 129 $$ {}^{129} $$ Xe in lipids was determined in one rat by fitting exponentials to decaying signals of global spin-echo spectra. Four rats (conventional CSI) and six rats (turbo spectroscopic imaging) were scanned at three time points with core body temperature 37/34/37 ∘ $$ {}^{\circ } $$ C. Lorentzian functions were fit to spectra from regions of interest to determine the water-referenced chemical shift of lipid-dissolved 129 $$ {}^{129} $$ Xe in the abdomen. Absolute 129 $$ {}^{129} $$ Xe-derived temperature was compared to values from a rectal probe. RESULTS: Global T 2 $$ {T}_2 $$ of 129 $$ {}^{129} $$ Xe in lipids was determined as 251 . 3 ms ± 81 . 4 ms $$ 251.3\;\mathrm{ms}\pm 81.4\;\mathrm{ms} $$ . Friedman tests showed significant changes of chemical shift with time for both sequence variants and both FID and spin-echo acquisitions. Mean and SD of 129 $$ {}^{129} $$ Xe and rectal probe temperature differences were found to be - 0 . 1 5 ∘ C ± 0 . 9 3 ∘ C $$ -0.1{5}^{\circ}\mathrm{C}\pm 0.9{3}^{\circ}\mathrm{C} $$ (FID) and - 0 . 3 8 ∘ C ± 0 . 6 4 ∘ C $$ -0.3{8}^{\circ}\mathrm{C}\pm 0.6{4}^{\circ}\mathrm{C} $$ (spin echo) for conventional CSI as well as 0 . 0 3 ∘ C ± 0 . 7 7 ∘ C $$ 0.0{3}^{\circ}\mathrm{C}\pm 0.7{7}^{\circ}\mathrm{C} $$ (FID) and - 0 . 0 6 ∘ C ± 0 . 7 6 ∘ C $$ -0.0{6}^{\circ}\mathrm{C}\pm 0.7{6}^{\circ}\mathrm{C} $$ (spin echo) for turbo spectroscopic imaging. CONCLUSION: 129 $$ {}^{129} $$ Xe MRI using conventional CSI and turbo spectroscopic imaging of lipid-dissolved 129 $$ {}^{129} $$ Xe enables precise temperature measurements in the rat's abdomen using both FID and spin-echo acquisitions with acquisition of spin echoes enabling most precise temperature measurements.

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 < 0.01). Spatial overlap of PREFUL and DCE QDP maps showed an agreement of 79.4% for the whole lung. Further, spatial overlap values of Center 1 were not significantly different to those of Center 2 for the three central slices (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.

Investigating short-time diffusion of hyperpolarized 129 Xe in lung air spaces and tissue: A feasibility study in chronic obstructive pulmonary disease patients.

PURPOSE: To investigate the diffusion of hyperpolarized 129 Xe in air spaces at short-time scales for determination of lung surface-to-gas-volume ratio in comparison to results from chemical shift saturation recovery, CT, and established clinical measures. METHODS: A pulse sequence for measurement of time-dependent diffusion of 129 Xe in air spaces at short diffusion times was developed. Gas uptake into lung tissue was measured in the same breathhold using chemical shift saturation recovery spectroscopy in the short-time regime. The potential to obtain the surface-to-gas-volume ratio using a first-order and second-order approximation of the short-time expansion of time-dependent diffusion according to Mitra et al11 and its diagnostic relevance were tested in a study with 9 chronic obstructive pulmonary diseases patients. RESULTS: Surface-to-gas-volume ratios obtained from time-dependent diffusion were correlated with results from chemical shift saturation recovery, r = 0.840, P = .005 (first-order fits), and r = 0.923, P < .001 (second-order fits), and from CT results for second-order fits, r = 0.729, P = .026. Group means ± SD were 75.0 ± 15.5 cm-1 (first-order fits) and 122.3 ± 32.8 cm-1 (second-order fits) for time-dependent diffusion, 125.9 ± 43.3 cm-1 for chemical shift saturation recovery, and 159.5 ± 50.9 cm-1 for CT. Surface-to-gas-volume ratios from time-dependent diffusion with first-order fits correlated significantly with carbon monoxide diffusing capacity as percent of prediction, r = 0.724, P = .028. CONCLUSION: Time-dependent diffusion measurements of 129 Xe at short-time scales down to ~1 ms are feasible in chronic obstructive pulmonary patients and provide clinically relevant information on lung microstructure.

Noninvasive Monitoring of the Response of Human Lungs to Low-Dose Lipopolysaccharide Inhalation Challenge Using MRI: A Feasibility Study.

BACKGROUND: Development of antiinflammatory drugs for lung diseases demands novel methods for noninvasive assessment of inflammatory processes in the lung. PURPOSE: To investigate the feasibility of hyperpolarized 129 Xe MRI, 1 H T1 time mapping, and dynamic contrast-enhanced (DCE) perfusion MRI for monitoring the response of human lungs to low-dose inhaled lipopolysaccharide (LPS) challenge compared to inflammatory cell counts from induced-sputum analysis. STUDY TYPE: Prospective feasibility study. POPULATION: Ten healthy volunteers underwent MRI before and 6 hours after inhaled LPS challenge with subsequent induced-sputum collection. FIELD STRENGTH/SEQUENCES: 1.5T/hyperpolarized 129 Xe MRI: Interleaved multiecho imaging of dissolved and gas phase, ventilation imaging, dissolved-phase spectroscopy, and chemical shift saturation recovery spectroscopy. 1 H MRI: Inversion recovery fast low-angle shot imaging for T1 mapping, time-resolved angiography with stochastic trajectories for DCE MRI. ASSESSMENT: Dissolved-phase ratios of 129 Xe in red blood cells (RBC), tissue/plasma (TP) and gas phase (GP), ventilation defect percentage, septal wall thickness, surface-to-volume ratio, capillary transit time, lineshape parameters in dissolved-phase spectroscopy, 1 H T1 time, blood volume, flow, and mean transit time were determined and compared to cell counts. STATISTICAL TESTS: Wilcoxon signed-rank test, Pearson correlation. RESULTS: The percentage of neutrophils in sputum was markedly increased after LPS inhalation compared to baseline, P = 0.002. The group median RBC-TP ratio was significantly reduced from 0.40 to 0.31, P = 0.004, and 1 H T1 was significantly elevated from 1157.6 msec to 1187.8 msec after LPS challenge, P = 0.027. DCE MRI exhibited no significant changes in blood volume, P = 0.64, flow, P = 0.17, and mean transit time, P = 0.11. DATA CONCLUSION: Hyperpolarized 129 Xe dissolved-phase MRI and 1 H T1 mapping may provide biomarkers for noninvasive assessment of the response of human lungs to LPS inhalation. By its specificity to the alveolar region, hyperpolarized 129 Xe MRI together with 1 H T1 mapping adds value to sputum analysis. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1669-1676.

Repeatability of Regional Lung Ventilation Quantification Using Fluorinated (19F) Gas Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: To assess the repeatability of global and regional lung ventilation quantification in both healthy subjects and patients with chronic obstructive pulmonary disease (COPD) using fluorinated (19F) gas washout magnetic resonance (MR) imaging in free breathing. MATERIAL AND METHODS: In this prospective institutional review board-approved study, 12 healthy nonsmokers and eight COPD patients were examined with 19F dynamic gas washout MR imaging in free breathing and with lung function testing. Measurements were repeated within 2 weeks. Lung ventilation was quantified using 19F gas washout time. Repeatability was analyzed for the total lung and on a regional basis using the coefficient of variation (COV) and Bland-Altman plots. RESULTS: In healthy subjects and COPD patients, a good repeatability was found for lung ventilation quantification using dynamic 19F gas washout MR imaging on a global (COV < 8%) and regional (COV < 15%) level. Gas washout time was significantly increased in the COPD group compared to the healthy subjects. CONCLUSION: 19F gas washout MR imaging provides a good repeatability of lung ventilation quantification and appears to be sensitive to early changes of regional lung function alterations such as normal aging.

Mapping of regional lung microstructural parameters using hyperpolarized 129 Xe 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 129 Xe 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 129 Xe 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 129 Xe 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.