Phase-Resolved Functional Lung MRI for Pulmonary Ventilation and Perfusion (V/Q) Assessment.

Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time series of each voxel is analyzed with regard to the cardiac and breathing frequency components. Using a standard 2D spoiled gradient-echo sequence with a temporal resolution of ~300 ms, an image-sorting algorithm was developed to produce phase-resolved functional lung imaging (PREFUL) with an increased temporal resolution. Thus, it is feasible to evaluate regional flow volume loops (FVL) during tidal volume breathing and depict the propagation of the pulse wave during the cardiac cycle. This method can be applied at 1.5T or 3T with standard MR hardware without the necessity for sequence programming, as the described protocol can be implemented with the default SPGRE sequence on most systems. PREFUL ventilation MRI has been validated using 129Xe and 19F gas imaging with good regional agreement. Perfusion-weighted PREFUL MRI has been validated using SPECT as well as dynamic contrast enhanced (DCE) MRI. PREFUL has been tested in a dual center dual vendor setting and is currently applied in several ongoing multicenter trials. Furthermore, it is feasible across a range of field strengths (0.55T-3T) and different age groups, including newborns. Quantitative V/Q PREFUL MRI has been used in patients with cystic fibrosis, chronic obstructive pulmonary disease, chronic thromboembolic pulmonary hypertension, and corona virus disease-2019 to quantify disease and monitor treatment change after therapy. Furthermore, PREFUL V/Q imaging has been shown to predict transplant loss due to chronic lung allograft dysfunction in patients after lung transplantation. In summary, PREFUL MRI is a validated technique for quantitative ventilation and pulmonary pulse wave/perfusion imaging for regional pulmonary disease detection, quantification, and treatment monitoring with potential added value to the current clinical routine.

Free-breathing 3D phase-resolved functional lung MRI vs breath-hold hyperpolarized 129Xe ventilation MRI in patients with chronic obstructive pulmonary disease and healthy volunteers.

OBJECTIVES: 3D phase-resolved functional lung (PREFUL) MRI offers evaluation of pulmonary ventilation without inhalation of contrast agent. This study seeks to compare ventilation maps obtained from 3D PREFUL MRI with a direct ventilation measurement derived from 129Xe MRI in both patients with chronic obstructive pulmonary disease (COPD) and healthy volunteers. METHODS: Thirty-one patients with COPD and 12 healthy controls underwent free-breathing 3D PREFUL MRI and breath-hold 129Xe MRI at 1.5 T. For both MRI techniques, ventilation defect (VD) maps were determined and respective ventilation defect percentage (VDP) values were computed. All parameters of both techniques were compared by Spearman correlation coefficient (r) and the differences between VDP values were quantified by Bland-Altman analysis and tested for significance using Wilcoxon signed-rank test. In a regional comparison of VD maps, spatial overlap and Sørensen-Dice coefficients of healthy and defect areas were computed. RESULTS: On a global level, all 3D PREFUL VDP values correlated significantly to VDP measure derived by 129Xe ventilation imaging (all r > 0.65; all p < 0.0001). 129Xe VDP was significantly greater than 3D PREFUL derived VDPRVent (mean bias = 10.5%, p < 0.001) and VDPFVL-CM (mean bias = 11.3%, p < 0.0001) but not for VDPCombined (mean bias = 1.7%, p = 0.70). The total regional agreement of 129Xe and 3D PREFUL VD maps ranged between 60% and 63%. CONCLUSIONS: Free-breathing 3D PREFUL MRI showed a strong correlation with breath-hold hyperpolarized 129Xe MRI regarding the VDP values and modest differences in the detection of VDs on a regional level. CLINICAL RELEVANCE STATEMENT: 3D PREFUL MRI correlated with 129Xe MRI, unveiling regional differences in COPD defect identification. This proposes 3D PREFUL MRI as a ventilation mapping surrogate, eliminating the need for extra hardware or inhaled gases. KEY POINTS: Current non-invasive evaluation techniques for lung diseases have drawbacks; 129Xe MRI is limited by cost and availability. 3D PREFUL MRI correlated with 129Xe MRI, with regional differences in identifying COPD defects. 3D PREFUL MRI can provide ventilation mapping without the need for additional hardware or inhaled gases.

Sequence comparison of spoiled gradient echo and balanced steady-state free precession for pulmonary free-breathing proton MRI in patients and healthy volunteers: Correspondence, repeatability, and validation with dynamic contrast-enhanced MRI.

Phase-resolved functional lung (PREFUL) MRI is a proton-based, contrast agent-free technique derived from the Fourier decomposition approach to measure regional ventilation and perfusion dynamics during free-breathing. Besides the necessity of extensive PREFUL postprocessing, the utilized MRI sequence must fulfill specific requirements. This study investigates the impact of sequence selection on PREFUL-MRI-derived functional parameters by comparing the standard spoiled gradient echo (SPGRE) sequence with a lung-optimized balanced steady-state free precession (bSSFP) sequence, thereby facilitating PREFULs clinical application in pulmonary disease assessment. This study comprised a prospective dataset of healthy volunteers and a retrospective dataset of patients with suspected chronic thromboembolic pulmonary hypertension. Both cohorts underwent PREFUL-MRI with both sequences to assess the correspondence of PREFUL ventilation and perfusion parameters (A). Additionally, healthy subjects were scanned a second time to evaluate repeatability (B), whereas patients received dynamic contrast-enhanced (DCE)-MRI, considered the perfusion gold standard for comparison with PREFUL-MRI (C). Signal-to-noise ratio (SNR), calculated from the unprocessed images, was compared alongside median differences of PREFUL-MRI-derived parameters using a paired Wilcoxon signed rank test. Further evaluations included calculation of the Pearson correlation, intraclass-correlation coefficient for repeatability assessment, and spatial overlap (SO) for regional comparison of PREFUL-MRI and DCE-MRI. bSSFP showed a clear SNR advantage over SPGRE (median: 23 vs. 9, p < 0.001). (A) Despite significant differences, parameter values were strongly correlated (r ≥ 0.75). After thresholding, binary maps showed high healthy overlap across both cohorts (SOHealthy > 86%) and high defect overlap in the patient cohort (SODefect ≥ 48%). (B) bSSFP demonstrated slightly higher repeatability across most parameters. (C) Both sequences demonstrated comparable correspondence to DCE-MRI, with SPGRE excelling in absolute quantification and bSSFP in spatial agreement. Although bSSFP showed superior SNR results, both sequences displayed spatial defect concordance and highly correlated PREFUL parameters with deviations regarding repeatability and alignment with DCE-MRI.

Three-Dimensional Phase Resolved Functional Lung Magnetic Resonance Imaging.

Pulmonary magnetic resonance imaging (MRI) offers a variety of radiation-free techniques tailored to assess regional lung ventilation or its surrogates. These techniques encompass direct measurements, exemplified by hyperpolarized gas MRI and fluorinated gas MRI, as well as indirect measurements facilitated by oxygen-enhanced MRI and proton-based Fourier decomposition (FD) MRI. In recent times, there has been substantial progress in the field of FD MRI, which involved improving spatial/temporal resolution, refining sequence design and postprocessing, and developing a comprehensive whole-lung approach. The two-dimensional (2D) phase-resolved functional lung (PREFUL) MRI stands out as an FD-based approach developed for the comprehensive assessment of regional ventilation and perfusion dynamics, all within a single MR acquisition. Recently, a new advancement has been made with the development of 3D PREFUL to assess dynamic ventilation of the entire lung using 8 min exam with a self-gated sequence. The 3D PREFUL acquisition involves employing a stack-of-stars spoiled-gradient-echo sequence with a golden angle increment. Following the compressed sensing image reconstruction of approximately 40 breathing phases, all the reconstructed respiratory-resolved images undergo registration onto a fixed breathing phase. Subsequently, the ventilation parameters are extracted from the registered images. In a study cohort comprising healthy volunteers and patients with chronic obstructive pulmonary disease, the 3D PREFUL ventilation parameters demonstrated strong correlations with measurements obtained from pulmonary function tests. Additionally, the interscan repeatability of the 3D PREFUL technique was deemed to be acceptable, indicating its reliability for repeated assessments of the same individuals. In summary, 3D PREFUL ventilation MRI provides a whole lung coverage and captures ventilation dynamics with enhanced spatial resolution compared to 2D PREFUL. 3D PREFUL technique offers a cost-effective alternative to hyperpolarized 129Xe MRI, making it an attractive option for patient-friendly evaluation of pulmonary ventilation.

Impact of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in children with cystic fibrosis and one or two F508del alleles.

BACKGROUND: We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children aged 6-11 years with CF and one or two F508del alleles. METHODS: This prospective, observational, multicentre, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and 3 months after initiation of ETI. RESULTS: A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (F/F) were enrolled in this study. Treatment with ETI improved the median (interquartile range (IQR)) LCI in F/MF (-1.0 (-2.0- -0.1); p<0.01) and F/F children (-0.8 (-1.9- -0.2); p<0.001) from 3 months onwards. Further, ETI improved the median (IQR) MRI global score in F/MF (-4.0 (-9.0-0.0); p<0.01) and F/F children (-3.5 (-7.3- -0.8); p<0.001). CONCLUSIONS: ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one F508del allele in a real-world setting. Our results support early initiation of ETI to reduce or even prevent lung disease progression in school-age children with CF.

Phase-Resolved Functional Lung (PREFUL) MRI May Reveal Distinct Pulmonary Perfusion Defects in Postacute COVID-19 Syndrome: Sex, Hospitalization, and Dyspnea Heterogeneity.

BACKGROUND: Pulmonary perfusion defects have been observed in patients with coronavirus disease 2019 (COVID-19). Currently, there is a need for further data on non-contrast-enhanced MRI in COVID patients. The early identification of heterogeneity in pulmonary perfusion defects among COVID-19 patients is beneficial for their timely clinical intervention and management. PURPOSE: To investigate the utility of phase-resolved functional lung (PREFUL) MRI in detecting pulmonary perfusion disturbances in individuals with postacute COVID-19 syndrome (PACS). STUDY TYPE: Prospective. SUBJECTS: Forty-four participants (19 females, mean age 64.1 years) with PACS and 44 healthy subjects (19 females, mean age 59.5 years). Moreover, among the 44 patients, there were 19 inpatients and 25 outpatients; 19 were female and 25 were male; 18 with non-dyspnea and 26 with dyspnea. FIELD STRENGTH/SEQUENCE: 3-T, two-dimensional (2D) spoiled gradient-echo sequence. ASSESSMENT: Ventilation and perfusion-weighted maps were extracted from five coronal slices using PREFUL analysis. Subsequently, perfusion defect percentage (QDP), ventilation defect percentage (VDP), and ventilation-perfusion match healthy (VQM) were calculated based on segmented lung parenchyma ventilation and perfusion-weighted maps. Additionally, clinical features, including demographic data (such as sex and age) and serum biomarkers (such as D-dimer levels), were evaluated. STATISTICAL TESTS: Spearman correlation coefficients to explore relationships between clinical features and QDP, VDP, and VQM. Propensity score matching analysis to reduce the confounding bias between patients with PACS and healthy controls. The Mann-Whitney U tests and Chi-squared tests to detect differences between groups. Multivariable linear regression analyses to identify factors related to QDP, VDP, and VQM. A P-value <0.05 was considered statistically significant. RESULTS: QDP significantly exceeded that of healthy controls in individuals with PACS (39.8% ± 15.0% vs. 11.0% ± 4.9%) and was significantly higher in inpatients than in outpatients (46.8% ± 17.0% vs. 34.5% ± 10.8%). Moreover, males exhibited pulmonary perfusion defects significantly more frequently than females (43.9% ± 16.8% vs. 34.4% ± 10.2%), and dyspneic participants displayed significantly higher perfusion defects than non-dyspneic patients (44.8% ± 15.8% vs. 32.6% ± 10.3%). QDP showed a significant positive relationship with age (ß = 0.50) and D-dimer level (ß = 0.72). DATA CONCLUSION: PREFUL MRI may show pulmonary perfusion defects in patients with PACS. Furthermore, perfusion impairments may be more pronounced in males, inpatients, and dyspneic patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Estimation of Cerebral Blood Flow Using the Pulse Wave Amplitude in Brain MRI.

RATIONALE AND OBJECTIVES: First, to test the feasibility of cerebral blood flow (CBF) estimation using the pulse wave amplitude in flow-related enhancement (FREE) brain MRI in comparison to pseudo-continuous arterial spin labeling (pCASL-MRI). Second, the potential for acceleration was evaluated retrospectively. MATERIALS AND METHODS: 24 healthy study participants between 20 and 61 years had cerebral MRI. Perfusion imaging was performed with a balanced steady-state free precession sequence for FREE-MRI and with pCASL-MRI for comparison. RESULTS: The value distribution of the estimated CBF showed a high overlap in the histogram between 0 and 20 mL/100 g/min. However, disparity of the values occurred with more values between 20 and 60 mL/100 g/min using pCASL-MRI and more high values > 60 mL/100 g/min applying FREE-MRI. A Kolmogorov-Smirnov test confirmed a differing probability distribution (P = 0.62). The approximated CBF from FREE-MRI remained stable until only 50% of the acquired data was used. Values from using 40% of the data increased significantly compared to 90% or more (P ≤ 0.05). Values within the white matter presented no significant change after data reduction. The global and voxel-wise correlation coefficients towards pCASL-MRI presented stability during data reduction of FREE-MRI. CONCLUSION: In conclusion, the proposed technique allows a rough approximation of the CBF compared to pCASL-MRI. Further sequence optimization must be achieved to improve the measurement of relatively lowly perfused tissues. Nevertheless, it offers large potential for imaging speed optimization and enables perfusion-weighted images similarly to the color Doppler mode in ultrasound.

PREFUL MRI for Monitoring Perfusion and Ventilation Changes after Elexacaftor-Tezacaftor-Ivacaftor Therapy for Cystic Fibrosis: A Feasibility Study.

Purpose To assess the feasibility of monitoring the effects of elexacaftor-tezacaftor-ivacaftor (ETI) therapy on lung ventilation and perfusion in people with cystic fibrosis (CF), using phase-resolved functional lung (PREFUL) MRI. Materials and Methods This secondary analysis of a multicenter prospective study was carried out between August 2020 and March 2021 and included participants 12 years or older with CF who underwent PREFUL MRI, spirometry, sweat chloride test, and lung clearance index assessment before and 8-16 weeks after ETI therapy. For PREFUL-derived ventilation and perfusion parameter extraction, two-dimensional coronal dynamic gradient-echo MR images were evaluated with an automated quantitative pipeline. T1- and T2-weighted MR images and PREFUL perfusion maps were visually assessed for semiquantitative Eichinger scores. Wilcoxon signed rank test compared clinical parameters and PREFUL values before and after ETI therapy. Correlation of parameters was calculated as Spearman ρ correlation coefficient. Results Twenty-three participants (median age, 18 years [IQR: 14-24.5 years]; 13 female) were included. Quantitative PREFUL parameters, Eichinger score, and clinical parameters (lung clearance index = 21) showed significant improvement after ETI therapy. Ventilation defect percentage of regional ventilation decreased from 18% (IQR: 14%-25%) to 9% (IQR: 6%-17%) (P = .003) and perfusion defect percentage from 26% (IQR: 18%-36%) to 19% (IQR: 13%-24%) (P = .002). Areas of matching normal (healthy) ventilation and perfusion increased from 52% (IQR: 47%-68%) to 73% (IQR: 61%-83%). Visually assessed perfusion scores did not correlate with PREFUL perfusion (P = .11) nor with ventilation-perfusion match values (P = .38). Conclusion The study demonstrates the feasibility of PREFUL MRI for semiautomated quantitative assessment of perfusion and ventilation changes in response to ETI therapy in people with CF. Keywords: Pediatrics, MR-Functional Imaging, Pulmonary, Lung, Comparative Studies, Cystic Fibrosis, Elexacaftor-Tezacaftor-Ivacaftor Therapy, Fourier Decomposition, PREFUL, Free-Breathing Proton MRI, Pulmonary MRI, Perfusion, Functional MRI, CFTR, Modulator Therapy, Kaftrio Clinical trial registration no. NCT04732910 Supplemental material is available for this article. © RSNA, 2024.

Alveolar membrane and capillary function in COVID-19 convalescents: insights from chest MRI.

OBJECTIVES: To investigate potential presence and resolution of longer-term pulmonary diffusion limitation and microvascular perfusion impairment in COVID-19 convalescents. MATERIALS AND METHODS: This prospective, longitudinal study was carried out between May 2020 and April 2023. COVID-19 convalescents repeatedly and age/sex-matched healthy controls once underwent MRI including hyperpolarized 129Xe MRI. Blood samples were obtained in COVID-19 convalescents for immunophenotyping. Ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP), and gas phase (GP) as well as lung surface-volume ratio were quantified and correlations with CD4+/CD8+ T cell frequencies were assessed using Pearson's correlation coefficient. Signed-rank tests were used for longitudinal and U tests for group comparisons. RESULTS: Thirty-five participants were recruited. Twenty-three COVID-19 convalescents (age 52.1 ± 19.4 years, 13 men) underwent baseline MRI 12.6 ± 4.2 weeks after symptom onset. Fourteen COVID-19 convalescents underwent follow-up MRI and 12 were included for longitudinal comparison (baseline MRI at 11.5 ± 2.7 weeks and follow-up 38.0 ± 5.5 weeks). Twelve matched controls were included for comparison. In COVID-19 convalescents, RBC-TP was increased at follow-up (p = 0.04). Baseline RBC-TP was lower in patients treated on intensive care unit (p = 0.03) and in patients with severe/critical disease (p = 0.006). RBC-TP correlated with CD4+/CD8+ T cell frequencies (R = 0.61/ - 0.60) at baseline. RBC-TP was not significantly different compared to matched controls at follow-up (p = 0.25). CONCLUSION: Impaired microvascular pulmonary perfusion and alveolar membrane function persisted 12 weeks after symptom onset and resolved within 38 weeks after COVID-19 symptom onset. CLINICAL RELEVANCE STATEMENT: 129Xe MRI shows improvement of microvascular pulmonary perfusion and alveolar membrane function between 11.5 ± 2.7 weeks and 38.0 ± 5.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease. KEY POINTS: • The study aims to investigate long-term effects of COVID-19 on lung function, in particular gas uptake efficiency, and on the cardiovascular system. • In COVID-19 convalescents, the ratio of 129Xe in red blood cells/tissue plasma increased longitudinally (p = 0.04), but was not different from matched controls at follow-up (p = 0.25). • Microvascular pulmonary perfusion and alveolar membrane function are impaired 11.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease at 38.0 weeks.

Feasibility, Repeatability, and Correlation to Lung Function of Phase-Resolved Functional Lung (PREFUL) MRI-derived Pulmonary Artery Pulse Wave Velocity Measurements.

BACKGROUND: Pulse wave velocity (PWV) in the pulmonary arteries (PA) is a marker of vascular stiffening. Currently, only phase-contrast (PC) MRI-based options exist to measure PA-PWV. PURPOSE: To test feasibility, repeatability, and correlation to clinical data of Phase-Resolved Functional Lung (PREFUL) MRI-based calculation of PA-PWV. STUDY TYPE: Retrospective. SUBJECTS: 79 (26 female) healthy subjects (age range 19-78), 58 (24 female) patients with chronic obstructive pulmonary disease (COPD, age range 40-77), 60 (33 female) patients with suspected pulmonary hypertension (PH, age range 28-85). SEQUENCE: 2D spoiled gradient echo, 1.5T. ASSESSMENT: PA-PWV was measured from PREFUL-derived cardiac cycles based on the determination of temporal and spatial distance between lung vasculature voxels using a simplified (sPWV) method and a more comprehensive (cPWV) method including more elaborate distance calculation. For 135 individuals, PC MRI-based PWV (PWV-QA) was measured. STATISTICAL TESTS: Intraclass-correlation-coefficient (ICC) and coefficient of variation (CoV) were used to test repeatability. Nonparametric tests were used to compare cohorts. Correlation of sPWV/cPWV, PWV-QA, forced expiratory volume in 1 sec (FEV1 ) %predicted, residual volume (RV) %predicted, age, and right heart catheterization (RHC) data were tested. Significance level α = 0.05 was used. RESULTS: sPWV and cPWV showed no significant differences between repeated measurements (P-range 0.10-0.92). CoV was generally lower than 15%. COPD and PH patients had significantly higher sPWV and cPWV than healthy subjects. Significant correlation was found between sPWV or cPWV and FEV1 %pred. (R = -0.36 and R = -0.44), but not with RHC (P-range -0.11 - 0.91) or age (P-range 0.23-0.89). Correlation to RV%pred. was significant for cPWV (R = 0.42) but not for sPWV (R = 0.34, P = 0.055). For all cohorts, sPWV and cPWV were significantly correlated with PWV-QA (R = -0.41 and R = 0.48). DATA CONCLUSION: PREFUL-derived PWV is feasible and repeatable. PWV is increased in COPD and PH patients and correlates to airway obstruction and hyperinflation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Comparison of Free-Breathing 3D Phase-Resolved Functional Lung (PREFUL) MRI With Dynamic 19 F Ventilation MRI in Patients With Obstructive Lung Disease and Healthy Volunteers.

BACKGROUND: Non-contrast-enhanced 1 H magnetic resonance imaging (MRI) with full lung coverage shows promise for assessment of regional lung ventilation but a comparison with direct ventilation measurement using 19 F MRI is lacking. PURPOSE: To compare ventilation parameters calculated using 3D phase-resolved functional lung (PREFUL) MRI with 19 F MRI. STUDY TYPE: Prospective. POPULATION: Fifteen patients with asthma, 14 patients with chronic obstructive lung disease, and 13 healthy volunteers. FIELD STRENGTH/SEQUENCE: A 3D gradient-echo pulse sequence with golden-angle increment and stack-of-stars encoding at 1.5 T. ASSESSMENT: All participants underwent 3D PREFUL MRI and 19 F MRI. For 3D PREFUL, static regional ventilation (RVent) and dynamic flow-volume cross-correlation metric (FVL-CM) were calculated. For both parameters, ventilation defect percentage (VDP) values and ventilation defect (VD) maps (including a combination of both parameters [VDPCombined ]) were determined. For 19 F MRI, images from eight consecutive breaths under volume-controlled inhalation of perfluoropropane were acquired. Time-to-fill (TTF) and wash-in (WI) parameters were extracted. For all 19 F parameters, a VD map was generated and the corresponding VDP values were calculated. STATISTICAL TESTS: For all parameters, the relationship between the two techniques was assessed using a Spearman correlation (r). Differences between VDP values were compared using Bland-Altman analysis. For regional comparison of VD maps, spatial overlap and Sørensen-Dice coefficients were computed. RESULTS: 3D PREFUL VDP values were significantly correlated to VDP measures by 19 F (r range: 0.59-0.70). For VDPRVent , no significant bias was observed with VDP of the third and fourth breath (bias range = -6.8:7.7%, P range = 0.25:0.30). For VDPFVL-CM , no significant bias was found with VDP values of fourth-eighth breaths (bias range = -2.0:12.5%, P range = 0.12:0.75). The overall spatial overlap of all VD maps increased with each breath, ranging from 61% to 81%, stabilizing at the fourth breath. DATA CONCLUSION: 3D PREFUL MRI parameters showed moderate to strong correlation with 19 F MRI. Depending on the 3D PREFUL VD map, the best regional agreement was found to 19 F VD maps of third-fifth breath. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Estimating ventilation correlation coefficients in the lungs using PREFUL-MRI in chronic obstructive pulmonary disease patients and healthy adults.

PURPOSE: Various parameters of regional lung ventilation can be estimated using phase-resolved functional lung (PREFUL)-MRI. The parameter "ventilation correlation coefficient (Vent-CC)" was shown advantageous because it assesses the dynamics of regional air flow. Calculating Vent-CC depends on a voxel-wise comparison to a healthy reference flow curve. This work examines the effect of placing a reference region of interest (ROI) in various lung quadrants or in different coronal slices. Furthermore, algorithms for automated ROI selection are presented and compared in terms of test-retest repeatability. METHODS: Twenty-eight healthy subjects and 32 chronic obstructive pulmonary disease (COPD) patients were scanned twice using PREFUL-MRI. Retrospective analyses examined the homogeneity of air flow curves of various reference ROIs using cross-correlation. Vent-CC and ventilation defect percentage (VDP) calculated using various reference ROIs were compared using one-way analysis of variance (ANOVA). The coefficient of variation was calculated for Vent-CC and VDP when using different reference selection algorithms. RESULTS: Flow-volume curves were highly correlated between ROIs placed at various lung quadrants in the same coronal slice (r > 0.97) with no differences in Vent-CC and VDP (ANOVA: p > 0.5). However, ROIs placed at different coronal slices showed lower correlation coefficients and resulted in significantly different Vent-CC and VDP values (ANOVA: p < 0.001). Vent-CC and VDP showed higher repeatability when calculated using the presented new algorithm. CONCLUSION: In COPD and healthy cohorts, assessing regional ventilation dynamics using PREFUL-MRI in terms of the Vent-CC metric showed higher repeatability using a new algorithm for selecting a homogenous reference ROI from the same slice.

Effect of CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor on pulmonary ventilation derived by 3D phase-resolved functional lung MRI in cystic fibrosis patients.

OBJECTIVES: To investigate whether 3D phase-resolved functional lung (PREFUL)-MRI parameters are suitable to measure response to elexacaftor/tezacaftor/ivacaftor (ETI) therapy and their association with clinical outcomes in cystic fibrosis (CF) patients. METHODS: Twenty-three patients with CF (mean age: 21; age range: 14-46) underwent MRI examination at baseline and 8-16 weeks after initiation of ETI. Morphological and 3D PREFUL scans assessed pulmonary ventilation. Morphological images were evaluated using a semi-quantitative scoring system, and 3D PREFUL scans were evaluated by ventilation defect percentage (VDP) values derived from regional ventilation (RVent) and cross-correlation maps. Improved ventilation volume (IVV) normalized to body surface area (BSA) between baseline and post-treatment visit was computed. Forced expiratory volume in 1 second (FEV1) and mid-expiratory flow at 25% of forced vital capacity (MEF25), as well as lung clearance index (LCI), were assessed. Treatment effects were analyzed using paired Wilcoxon signed-rank tests. Treatment changes and post-treatment agreement between 3D PREFUL and clinical parameters were evaluated by Spearman's correlation. RESULTS: After ETI therapy, all 3D PREFUL ventilation markers (all p < 0.0056) improved significantly, except for the mean RVent parameter. The BSA normalized IVVRVent was significantly correlated to relative treatment changes of MEF25 and mucus plugging score (all |r| > 0.48, all p < 0.0219). In post-treatment analyses, 3D PREFUL VDP values significantly correlated with spirometry, LCI, MRI global, morphology, and perfusion scores (all |r| > 0.44, all p < 0.0348). CONCLUSIONS: 3D PREFUL MRI is a very promising tool to monitor CFTR modulator-induced regional dynamic ventilation changes in CF patients. CLINICAL RELEVANCE STATEMENT: 3D PREFUL MRI is sensitive to monitor CFTR modulator-induced regional ventilation changes in CF patients. Improved ventilation volume correlates with the relative change of mucus plugging, suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement. KEY POINTS: • 3D PREFUL MRI-derived ventilation maps show significantly reduced ventilation defects in CF patients after ETI therapy. • Significant post-treatment correlations of 3D PREFUL ventilation measures especially with LCI, FEV1 %pred, and global MRI score suggest that 3D PREFUL MRI is sensitive to measure improved regional ventilation of the lung parenchyma due to reduced inflammation induced by ETI therapy in CF patients. • 3D PREFUL MRI-derived improved ventilation volume (IVV) correlated with MRI mucus plugging score changes suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement 8-16 weeks after ETI therapy.

Cerebral microcirculatory pulse wave propagation and pulse wave amplitude mapping in retrospectively gated MRI.

To analyze cerebral arteriovenous pulse propagation and to generate phase-resolved pulse amplitude maps from a fast gradient-echo sequence offering flow-related enhancement (FREE). Brain MRI was performed using a balanced steady-state free precession sequence at 3T followed by retrospective k-space gating. The time interval of the pulse wave between anterior-, middle- and posterior cerebral artery territories and the superior sagittal sinus were calculated and compared between and older and younger groups within 24 healthy volunteers. Pulse amplitude maps were generated and compared to pseudo-Continuous Arterial Spin Labeling (pCASL) MRI maps by voxel-wise Pearson correlation, Sørensen-Dice maps and in regards to signal contrast. The arteriovenous delays between all vascular territories and the superior sagittal sinus were significantly shorter in the older age group (11 individuals, ≥ 31 years) ranging between 169 ± 112 and 246 ± 299 ms versus 286 ± 244 to 419 ± 299 ms in the younger age group (13 individuals) (P ≤ 0.04). The voxel-wise pulse wave amplitude values and perfusion-weighted pCASL values correlated significantly (Pearson-r = 0.33, P < 0.01). Mean Dice overlaps of high (gray) and low (white matter) regions were 73 ± 3% and 59 ± 5%. No differences in image contrast were seen in the whole brain and the white matter, but significantly higher mean contrast of 0.73 ± 0.23% in cortical gray matter in FREE-MRI compared to 0.52 ± 0.12% in pCASL-MRI (P = 0.01). The dynamic information of flow-related enhancement allows analysis of the cerebral pulse wave propagation potentially providing information about the (micro)circulation on a regional level. However, the pulse wave amplitude reveals weaknesses in comparison to true perfusion-weighting and could rather be used to calculate a pulsatility index.

Diagnostic accuracy of perfusion-weighted phase-resolved functional lung magnetic resonance imaging in patients with chronic pulmonary embolism.

Purpose: This study aimed to evaluate the diagnostic performance of perfusion-weighted phase-resolved functional lung (PW-PREFUL) magnetic resonance imaging (MRI) in patients with chronic pulmonary embolism (CPE). Materials and methods: This study included 86 patients with suspected chronic thromboembolic pulmonary hypertension (CTEPH), who underwent PREFUL MRI and ventilation/perfusion (V/Q) single-photon emission computed tomography/computed tomography (SPECT/CT). PREFUL MRI was performed at 1.5 T using a balanced steady-state free precession sequence during free breathing. Color-coded PW images and quantitative parameters were obtained by postprocessing. Meanwhile, V/Q SPECT/CT imaging was performed as a reference standard. Hypoperfused areas in the lungs were scored for each lobe and segment using V/Q SPECT/CT images and PW-PREFUL MR images, respectively. Normalized perfusion (QN) and perfusion defect percentage (QDP) were calculated for all slices. For intra- and interobserver variability, the MRI images were analyzed 2 months after the first analysis by the same radiologist and another radiologist (11 years of lung MRI experience) blinded to the results of the first reader. Results: Of the 86 enrolled patients, 77 met the inclusion criteria (36 diagnosed with CPE using V/Q SPECT/CT and 41 diagnosed with non-CPE etiology). For the PW-PREFUL MRI, the sensitivity, specificity, accuracy, and positive and negative predictive values for the diagnosis of CPE were 97, 95, 96, 95, and 98% at the patient level; 91, 94, 93, 91, and 94% at the lobe level, and 85, 94, 92, 88, and 94% at the segment level, respectively. The detection of segmental and subsegmental hypoperfusion using PW-PREFUL MRI revealed a moderate agreement with V/Q SPECT/CT (κ = 0.65; 95% confidence interval: 0.61-0.68). The quantitative results indicated that the QN was lower in the CPE group than in the non-CPE group [median score (interquartile range, IQR) 6.3 (2.8-9.2) vs. 13.0 (8.8-16.7), p < 0.001], and the QDP was higher [median score (IQR) 33.8 (15.7-51.7) vs. 2.2 (1.4-2.9), p < 0.001]. Conclusion: PREFUL MRI could be an alternative test to detect CPE without requiring breath-hold, contrast agents, or ionizing radiation.

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 1.

Influence of gadolinium, field-strength and sequence type on quantified perfusion values in phase-resolved functional lung MRI.

PURPOSE: The purpose of this study is to evaluate the influences of gadolinium-based contrast agents, field-strength and different sequences on perfusion quantification in Phase-Resolved Functional Lung (PREFUL) MRI. MATERIALS AND METHODS: Four cohorts of different subjects were imaged to analyze influences on the quantified perfusion maps: 1) at baseline and after 2 weeks to obtain the reproducibility (26 COPD patients), 2) before and after the administration of gadobutrol (11 COPD, 2 PAH and 1 asthma), 3) at 1.5T and 3T (12 healthy, 4 CF), and 4) with different acquisition sequences spoiled gradient echo (SPGR) and balanced steady-state free precession (bSSFP) (11 COPD, 7 healthy). Wilcoxon-signed rank test, Bland-Altman plots, voxelwise Pearson correlations, normalized histogram analyses with skewness and kurtosis and two-sample Kolmogorov-Smirnov tests were performed. P value ≤ 0.05 was considered statistically significant. RESULTS: In all cohorts, linear correlations of the perfusion values were significant with correlation coefficients of at least 0.7 considering the entire lung (P<0.01). The reproducibility cohort revealed stable results with a similar distribution. In the gadolinium cohort, the quantified perfusion increased significantly (P<0.01), and no significant change was detected in the histogram analysis. In the field-strength cohort, no significant change of the quantified perfusion was shown, but a significant increase of skewness and kurtosis at 3T (P = 0.01). In the sequence cohort, the quantified perfusion decreased significantly in the bSSFP sequence (P<0.01) together with a significant decrease of skewness and kurtosis (P = 0.02). The field-strength and sequence cohorts had differing probability distribution in the two-sample Kolmogorov-Smirnov tests. CONCLUSION: We observed a high susceptibility of perfusion quantification to gadolinium, field-strength or MRI sequence leading to distortion and deviation of the perfusion values. Future multicenter studies should strictly adhere to the identical study protocols to generate comparable results.

Artificially-generated consolidations and balanced augmentation increase performance of U-net for lung parenchyma segmentation on MR images.

PURPOSE: To improve automated lung segmentation on 2D lung MR images using balanced augmentation and artificially-generated consolidations for training of a convolutional neural network (CNN). MATERIALS AND METHODS: From 233 healthy volunteers and 100 patients, 1891 coronal MR images were acquired. Of these, 1666 images without consolidations were used to build a binary semantic CNN for lung segmentation and 225 images (187 without consolidations, 38 with consolidations) were used for testing. To increase CNN performance of segmenting lung parenchyma with consolidations, balanced augmentation was performed and artificially-generated consolidations were added to all training images. The proposed CNN (CNNBal/Cons) was compared to two other CNNs: CNNUnbal/NoCons-without balanced augmentation and artificially-generated consolidations and CNNBal/NoCons-with balanced augmentation but without artificially-generated consolidations. Segmentation results were assessed using Sørensen-Dice coefficient (SDC) and Hausdorff distance coefficient. RESULTS: Regarding the 187 MR test images without consolidations, the mean SDC of CNNUnbal/NoCons (92.1 ± 6% (mean ± standard deviation)) was significantly lower compared to CNNBal/NoCons (94.0 ± 5.3%, P = 0.0013) and CNNBal/Cons (94.3 ± 4.1%, P = 0.0001). No significant difference was found between SDC of CNNBal/Cons and CNNBal/NoCons (P = 0.54). For the 38 MR test images with consolidations, SDC of CNNUnbal/NoCons (89.0 ± 7.1%) was not significantly different compared to CNNBal/NoCons (90.2 ± 9.4%, P = 0.53). SDC of CNNBal/Cons (94.3 ± 3.7%) was significantly higher compared to CNNBal/NoCons (P = 0.0146) and CNNUnbal/NoCons (P = 0.001). CONCLUSIONS: Expanding training datasets via balanced augmentation and artificially-generated consolidations improved the accuracy of CNNBal/Cons, especially in datasets with parenchymal consolidations. This is an important step towards a robust automated postprocessing of lung MRI datasets in clinical routine.

Phase-resolved Functional Lung (PREFUL) MRI-derived Ventilation and Perfusion Parameters Predict Future Lung Transplant Loss.

Background Chronic lung allograft dysfunction (CLAD), the physiologic correlate of chronic rejection, remains a major barrier to long-term survival following lung transplant. Biomarkers for early prediction of future transplant loss or death due to CLAD might open a window of opportunity for early diagnosis and treatment of CLAD. Purpose To evaluate the prognostic use of phase-resolved functional lung (PREFUL) MRI in predicting CLAD-related transplant loss or death. Materials and Methods In this prospective, longitudinal, single-center study, PREFUL MRI-derived ventilation and parenchymal lung perfusion parameters of bilateral lung transplant recipients without clinically suspected CLAD were assessed 6-12 months (baseline) and 2.5 years (follow-up) after transplant. MRI scans were acquired between August 2013 and December 2018. Regional flow volume loop (RFVL)-based ventilated volume (VV) and perfused volume were calculated using thresholds and spatially combined as ventilation-perfusion (V/Q) matching. Spirometry data were obtained on the same day. Exploratory models were calculated using receiver operating characteristic analysis, and subsequent survival analyses (Kaplan-Meier, hazard ratios [HRs]) of CLAD-related graft loss were performed to compare clinical and MRI parameters as clinical end points. Results At baseline MRI examination, 132 clinically stable patients of 141 patients (median age, 53 years [IQR, 43-59 years]; 78 men) were included (nine were excluded for deaths not associated with CLAD), 24 of which had CLAD-related graft loss (death or retransplant) within the observational period of 5.6 years. PREFUL MRI-derived RFVL VV was a predictor of poorer survival (cutoff, 92.3%; log-rank P = .02; HR for graft loss, 2.5 [95% CI: 1.1, 5.7]; P = .02), while perfused volume (P = .12) and spirometry (P = .33) were not predictive of differences in survival. In the evaluation of percentage change at follow-up MRI (92 stable patients vs 11 with CLAD-related graft loss), mean RFVL (cutoff, 97.1%; log-rank P < .001; HR, 7.7 [95% CI: 2.3, 25.3]), V/Q defect (cutoff, 498%; log-rank P = .003; HR, 6.6 [95% CI: 1.7, 25.0]), and forced expiratory volume in the first second of expiration (cutoff, 60.8%; log-rank P < .001; HR, 7.9 [95% CI: 2.3, 27.4]; P = .001) were predictive of poorer survival within 2.7 years (IQR, 2.2-3.5 years) after follow-up MRI. Conclusion Phase-resolved functional lung MRI ventilation-perfusion matching parameters were predictive of future chronic lung allograft dysfunction-related death or transplant loss in a large prospective cohort who had undergone lung transplant. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Fain and Schiebler in this issue.

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.