Functional Lung MRI Research Articles

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.

Phase-resolved MRI for measurement of pulmonary perfusion and ventilation defects in comparison with dynamic contrast-enhanced MRI and 129Xe MRI

IntroductionThis meta-analysis aims to evaluate the agreement and correlation between phase-resolved functional lung MRI (PREFUL MRI) and dynamic contrast-enhanced (DCE) MRI in evaluating perfusion defect percentage (QDP), as well as...

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

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. 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. 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%. Free-breathing3D 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. 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. 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. 3DPREFUL 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.

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

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. To investigate the utility of phase-resolved functional lung (PREFUL) MRI in detecting pulmonary perfusion disturbances in individuals with postacute COVID-19 syndrome (PACS). Prospective. 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. 3-T, two-dimensional (2D) spoiled gradient-echo sequence. 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. 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. 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 (β = 0.50) and D-dimer level (β = 0.72). PREFUL MRI may show pulmonary perfusion defects in patients with PACS. Furthermore, perfusion impairments may be more pronounced in males, inpatients, and dyspneic patients. 2 TECHNICAL EFFICACY: Stage 2.

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

ObjectivesTo 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.MethodsTwenty-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.ResultsAfter 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).Conclusions3D PREFUL MRI is a very promising tool to monitor CFTR modulator–induced regional dynamic ventilation changes in CF patients.Clinical relevance statement3D 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.

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

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. 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. 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. 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.

Non-Contrast-Enhanced Functional Lung MRI to Evaluate Treatment Response of Allergic Bronchopulmonary Aspergillosis in Patients With Cystic Fibrosis: A Pilot Study.

Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is associated with severe lung damage and requires specific therapeutic management. Repeated imaging is recommended to both diagnose and follow-up response to treatment of ABPA in CF. However, high risk of cumulative radiation exposure requires evaluation of free-radiation techniques in the follow-up of CF patients with ABPA. To evaluate whether Fourier decomposition (FD) functional lung MRI can detect response to treatment of ABPA in CF patients. Retrospective longitudinal. Twelve patients (7M, median-age:14 years) with CF and ABPA with pre- and post-treatment MRI. 2D-balanced-steady-state free-precession (bSSFP) sequence with FD at 1.5T. Ventilation-weighted (V) and perfusion-weighted (Q) maps were obtained after FD processing of 2D-coronal bSSFP time-resolved images acquired before and 3-9 months after treatment. Defects extent was assessed on the functional maps using a qualitative semi-quantitative score (0 = absence/negligible, 1 = <50%, 2 = >50%). Mean and coefficient of variation (CV) of the ventilation signal-intensity (VSI) and the perfusion signal-intensity (QSI) were calculated. Measurements were performed independently by three readers and averaged. Inter-reader reproducibility of the measurements was assessed. Pulmonary function tests (PFTs) were performed within 1 week of both MRI studies as markers of the airflow-limitation severity. Comparisons of medians were performed using the paired Wilcoxon-test. Reproducibility was assessed using intraclass correlation coefficient (ICC). Correlations between MRI and PFT parameters were assessed using the Spearman-test (rho correlation-coefficient). A P-value <0.05 was considered as significant. Defects extent on both V and Q maps showed a significant reduction after ABPA treatment (4.25 vs. 1.92 for V-defect-score and 5 vs. 2.75 for Q-defect-score). VSI_mean was significantly increased after treatment (280 vs. 167). Qualitative analyses reproducibility showed an ICC > 0.90, while the ICCs of the quantitative measurements was almost perfect (>0.99). Changes in VSI_cv and QSI_cv before and after treatment correlated inversely with changes of FEV1%p (rho = -0.68 for both). Non-contrast-enhanced FD lung MRI has potential to reproducibly assess response to treatment of ABPA in CF patients and correlates with PFT obstructive parameters. 4 TECHNICAL EFFICACY: Stage 3.

Motion-compensated low-rank reconstruction for simultaneous structural and functional UTE lung MRI.

Three-dimensional UTE MRI has shown the ability to provide simultaneous structural and functional lung imaging, but it is limited by respiratory motion and relatively low lung parenchyma SNR. The purpose of this paper is to improve this imaging by using a respiratory phase-resolved reconstruction approach, named motion-compensated low-rank reconstruction (MoCoLoR), which directly incorporates motion compensation into a low-rank constrained reconstruction model for highly efficient use of the acquired data. The MoCoLoR reconstruction is formulated as an optimization problem that includes a low-rank constraint using estimated motion fields to reduce the rank, optimizing over both the motion fields and reconstructed images. The proposed reconstruction along with XD and motion state-weighted motion-compensation (MostMoCo) methods were applied to 18 lung MRI scans of pediatric and young adult patients. The data sets were acquired under free-breathing and without sedation with 3D radial UTE sequences in approximately 5 min. After reconstruction, they went through ventilation analyses. Performance across reconstruction regularization and motion-state parameters were also investigated. The in vivo experiments results showed that MoCoLoR made efficient use of the data, provided higher apparent SNR compared with state-of-the-art XD reconstruction and MostMoCo reconstructions, and yielded high-quality respiratory phase-resolved images for ventilation mapping. The method was effective across the range of patients scanned. The motion-compensated low-rank regularized reconstruction approach makes efficient use of acquired data and can improve simultaneous structural and functional lung imaging with 3D-UTE MRI. It enables the scanning of pediatric patients under free-breathing and without sedation.

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.

Ventilation and perfusion MRI at a 0.35 T MR-Linac: feasibility and reproducibility study

BackgroundHybrid devices that combine radiation therapy and MR-imaging have been introduced in the clinical routine for the treatment of lung cancer. This opened up not only possibilities in terms of accurate tumor tracking, dose delivery and adapted treatment planning, but also functional lung imaging. The aim of this study was to show the feasibility of Non-uniform Fourier Decomposition (NuFD) MRI at a 0.35 T MR-Linac as a potential treatment response assessment tool, and propose two signal normalization strategies for enhancing the reproducibility of the results.MethodsTen healthy volunteers (median age 28 ± 8 years, five female, five male) were repeatedly scanned at a 0.35 T MR-Linac using an optimized 2D+t balanced steady-state free precession (bSSFP) sequence for two coronal slice positions. Image series were acquired in normal free breathing with breaks inside and outside the scanner as well as deep and shallow breathing. Ventilation- and perfusion-weighted maps were generated for each image series using NuFD. For intra-volunteer ventilation map reproducibility, a normalization factor was defined based on the linear correlation of the ventilation signal and diaphragm position of each scan as well as the diaphragm motion amplitude of a reference scan. This allowed for the correction of signal dependency on the diaphragm motion amplitude, which varies with breathing patterns. The second strategy, which can be used for ventilation and perfusion, eliminates the dependency on the signal amplitude by normalizing the ventilation/perfusion maps with the average ventilation/perfusion signal within a selected region-of-interest (ROI). The position and size dependency of this ROI was analyzed. To evaluate the performance of both approaches, the normalized ventilation/perfusion-weighted maps were compared and the deviation of the mean ventilation/perfusion signal from the reference was calculated for each scan. Wilcoxon signed-rank tests were performed to test whether the normalization methods can significantly improve the reproducibility of the ventilation/perfusion maps.ResultsThe ventilation- and perfusion-weighted maps generated with the NuFD algorithm demonstrated a mostly homogenous distribution of signal intensity as expected for healthy volunteers regardless of the breathing maneuver and slice position. Evaluation of the ROI’s size and position dependency showed small differences in the performance. Applying both normalization strategies improved the reproducibility of the ventilation by reducing the median deviation of all scans to 9.1%, 5.7% and 8.6% for the diaphragm-based, the best and worst performing ROI-based normalization, respectively, compared to 29.5% for the non-normalized scans. The significance of this improvement was confirmed by the Wilcoxon signed rank test with p, <, 0.01 at alpha , =, 0.05. A comparison of the techniques against each other revealed a significant difference in the performance between best ROI-based normalization and worst ROI (p, =, 0.01) and between best ROI-based normalization and scaling factor (p, =, 0.02), but not between scaling factor and worst ROI (p, =, 0.71). Using the ROI-based approach for the perfusion-maps, the uncorrected deviation of 10.2% was reduced to 5.3%, which was shown to be significant (p, <, 0.01).ConclusionsUsing NuFD for non-contrast enhanced functional lung MRI at a 0.35 T MR-Linac is feasible and produces plausible ventilation- and perfusion-weighted maps for volunteers without history of chronic pulmonary diseases utilizing different breathing patterns. The reproducibility of the results in repeated scans significantly benefits from the introduction of the two normalization strategies, making NuFD a potential candidate for fast and robust early treatment response assessment of lung cancer patients during MR-guided radiotherapy.

Effects of elexacaftor/tezacaftor/ivacaftor therapy in children with cystic fibrosis – a comprehensive assessment using lung clearance index, spirometry, and functional and structural lung MRI

With improvement in supportive therapies and the introduction of cystic fibrosis transmembrane conductance regulator (CFTR)-modulator treatment in patients with cystic fibrosis (CF), milder disease courses are expected. Therefore, sensitive parameters are needed to monitor disease course and effects of CFTR-modulators. Functional lung MRI using matrix-pencil decomposition (MP-MRI) is a promising tool for assessing ventilation and perfusion quantitatively. This study aimed to assess the treatment effect of elexacaftor/tezacaftor/ivacaftor combination regimen (ELX/TEZ/IVA) on measures of structural and functional lung abnormalities. 24 children with CF underwent lung function tests (multiple breath washout, spirometry), functional and structural MRI twice (one year apart) before and once after at least two weeks (mean 4.7±2.6 months) on ELX/TEZ/IVA. Main outcomes were changes (Δ) upon ELX/TEZ/IVA in lung function, defect percentage of ventilation (VDP) and perfusion (QDP), defect distribution index of ventilation and perfusion (DDIV, DDIQ), and Eichinger score. Statistical analyses were performed using paired t-tests and multilevel regression models with bootstrapping. We observed a significant improvement in lung function, structural and functional MRI parameters upon ELX/TEZ/IVA treatment (mean; 95%-CI): ΔLCI2.5 (TO) -0.84 (-1.62 to -0.06); ΔFEV1 (z-score) 1.05 (0.56 to 1.55); ΔVDP (% of impairment) -6.00 (-8.44 to -3.55); ΔQDP (% of impairment) -3.90 (-5.90 to -1.90); ΔDDIV -1.38 (-2.22 to -0.53); ΔDDIQ -0.31 (-0.73 to 0.12); ΔEichinger score -3.89 (-5.05 to -2.72). Besides lung function tests, functional and structural MRI is a suitable tool to monitor treatment response of ELX/TEZ/IVA therapy, and seems promising as outcome marker in the future.

Inter- and intravisit repeatability of free-breathing MRI in pediatric cystic fibrosis lung disease.

The purpose of this study is to assess the intra- and interscan repeatability of free-breathing phase-resolved functional lung (PREFUL) MRI in stable pediatric cystic fibrosis (CF) lung disease in comparison to static breath-hold hyperpolarized 129-xenon MRI (Xe-MRI) and pulmonary function tests. Free-breathing 1-hydrogen MRI and Xe-MRI were acquired from 15 stable pediatric CF patients and seven healthy age-matched participants on two visits, 1 month apart. Same-visit MRI scans were also performed on a subgroup of the CF patients. Following the PREFUL algorithm, regional ventilation (RVent) and regional flow volume loop cross-correlation maps were determined from the free-breathing data. Ventilation defect percentage (VDP) was determined from RVent maps (VDPRVent ), regional flow volume loop cross-correlation maps (VDPCC ), VDPRVent ∪ VDPCC , and multi-slice Xe-MRI. Repeatability was evaluated using Bland-Altman analysis, coefficient of repeatability (CR), and intraclass correlation. Minimal bias and no significant differences were reported for all PREFUL MRI and Xe-MRI VDP parameters between intra- and intervisits (all P > 0.05). Repeatability of VDPRVent , VDPCC , VDPRVent ∪ VDPCC , and multi-slice Xe-MRI were lower between the two-visit scans (CR=14.81%, 15.36%, 16.19%, and 9.32%, respectively) in comparison to the same-day scans (CR=3.38%, 2.90%, 1.90%, and 3.92%, respectively). pulmonary function tests showed high interscan repeatability relative to PREFUL MRI and Xe-MRI. PREFUL MRI, similar to Xe-MRI, showed high intravisit repeatability but moderate intervisit repeatability in CF, which may be due to inherent disease instability, even in stable patients. Thus, PREFUL MRI may be considered a suitable outcome measure for future treatment response studies.

Feasibility of flow-related enhancement brain perfusion MRI.

Brain perfusion imaging is of enormous importance for various neurological diseases. Fast gradient-echo sequences offering flow-related enhancement (FREE) could present a basis to generate perfusion-weighted maps. In this study, we obtained perfusion-weighted maps without contrast media by a previously described postprocessing algorithm from the field of functional lung MRI. At first, the perfusion signal was analyzed in fast low-angle shot (FLASH) and balanced steady-state free precession (bSSFP) sequences. Secondly, perfusion maps were compared to pseudo-continuous arterial spin labeling (pCASL) MRI in a healthy cohort. Thirdly, the feasibility of the new technique was demonstrated in a small selected group of patients with metastases and acute stroke. One participant was examined with bSSFP and FLASH sequences at 1.5T and 3T, different flip angles and slice thicknesses. Twenty-five volunteers had bSSFP imaging and pCASL MRI. Three patients with cerebral metastases and one with acute ischemic stroke had bSSFP imaging and were compared to T1 post-contrast images and CT perfusion. Frequency analyses, SNR and perfusion contrast were compared at different flip angles and slice thicknesses. Regional correlations and Sorensen-Dice overlap were calculated in the healthy cohort. Dice overlap of the pathologies in the patient cohort were calculated. The bSSFP sequence presented detectable perfusion signal within brain vessel and parenchyma together with superior SNR compared to FLASH. Perfusion contrast and its corticomedullary differentiation increased with flip angle. Mean regional correlation was 0.36 and highly significant between FREE maps and pCASL and grey and white matter Dice match were 72% and 60% in the healthy cohort. Pathologies presented good overlap between FREE perfusion-weighted and T1 post-contrast images. The feasibility of FREE brain perfusion imaging has been shown in a healthy cohort and selected patient cases with brain metastases and acute stroke. The study demonstrates a new approach for non-contrast brain perfusion imaging.

Reproducibility of lung perfusion and ventilation derived using phase-resolved functional lung (PREFUL) MRI imaging

Abstract Background There is a growing demand for non-invasive imaging biomarkers of lung function, allowing more sensitive and timely decision making to achieve better patient outcomes. Recently developed Fourier decomposition MRI methods enable quantitative assessment of lung performance. Objectives To assess intra- and inter-observer agreement of lung perfusion and ventilation derived using the free-breathing, contrast agent-free, phase-resolved functional lung (PREFUL) imaging. Methods Fifty patients with acute ST-segment elevation myocardial infarction underwent CMR imaging using a 3 T MRI scanner (MAGNETOM Skyra). Coronal images were acquired during free breathing, covering the entire lung using a phase-resolved functional lung 2D FLASH sequence. The main scan parameters were: temporal resolution = 2.1 ms, number of measurements = 250. The lung perfusion and ventilation maps were generated (Figure 1). The analysis of the images was performed using prototype software (MR Lung Prototype version 2.0) by two independent observers. Analysis was repeated after four weeks to assess intra-observer agreement. Results PREFUL imaging and analysis were fast with a 35 second scan time and up to one minute post-processing time for a complete quantitative assessment. The lung perfusion and ventilation demonstrated excellent intra-observer (ICC 0.928 (0.870 to 0.959) and 0.994 (0.990 to 0.997) for mean perfusion and ventilation respectively) and inter-observer agreement (ICC 0.966 (0.940 to 0.981) and 0.992 (0.985 to 0.996) for mean perfusion and ventilation respectively). Bland-Altman plots demonstrate intra- and inter-observer reproducibility for lung perfusion and ventilation (Figure 2). Conclusion The lung perfusion and ventilation derived using phase-resolved functional lung (PREFUL) MRI imaging are highly reproducible. The Fourier decomposition method may allow fast quantitative evaluation of lung function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Hospital of Lithuanian University of Health Sciences

Large-scale investigation of deep learning approaches for ventilated lung segmentation using multi-nuclear hyperpolarized gas MRI

Respiratory diseases are leading causes of mortality and morbidity worldwide. Pulmonary imaging is an essential component of the diagnosis, treatment planning, monitoring, and treatment assessment of respiratory diseases. Insights into numerous pulmonary pathologies can be gleaned from functional lung MRI techniques. These include hyperpolarized gas ventilation MRI, which enables visualization and quantification of regional lung ventilation with high spatial resolution. Segmentation of the ventilated lung is required to calculate clinically relevant biomarkers. Recent research in deep learning (DL) has shown promising results for numerous segmentation problems. Here, we evaluate several 3D convolutional neural networks to segment ventilated lung regions on hyperpolarized gas MRI scans. The dataset consists of 759 helium-3 (3He) or xenon-129 (129Xe) volumetric scans and corresponding expert segmentations from 341 healthy subjects and patients with a wide range of pathologies. We evaluated segmentation performance for several DL experimental methods via overlap, distance and error metrics and compared them to conventional segmentation methods, namely, spatial fuzzy c-means (SFCM) and K-means clustering. We observed that training on combined 3He and 129Xe MRI scans using a 3D nn-UNet outperformed other DL methods, achieving a mean ± SD Dice coefficient of 0.963 ± 0.018, average boundary Hausdorff distance of 1.505 ± 0.969 mm, Hausdorff 95th percentile of 5.754 ± 6.621 mm and relative error of 0.075 ± 0.039. Moreover, limited differences in performance were observed between 129Xe and 3He scans in the testing set. Combined training on 129Xe and 3He yielded statistically significant improvements over the conventional methods (p < 0.0001). In addition, we observed very strong correlation and agreement between DL and expert segmentations, with Pearson correlation of 0.99 (p < 0.0001) and Bland–Altman bias of − 0.8%. The DL approach evaluated provides accurate, robust and rapid segmentations of ventilated lung regions and successfully excludes non-lung regions such as the airways and artefacts. This approach is expected to eliminate the need for, or significantly reduce, subsequent time-consuming manual editing.

PREFUL MRI Depicts Dual Bronchodilator Changes in COPD: A Retrospective Analysis of a Randomized Controlled Trial.

PurposeTo assess whether dynamic ventilation and perfusion (Q) biomarkers derived by phase-resolved functional lung (PREFUL) MRI can measure treatment response to 14-day therapy with indacaterol-glycopyrronium (IND-GLY) and correlate to clinical outcomes including lung function, symptoms, and cardiac function in patients with chronic obstructive pulmonary disease (COPD), as determined by spirometry, body plethysmography, cardiac MRI, and dyspnea score measurements.Materials and MethodsThe cardiac left ventricular function in COPD (CLAIM) study enrolled patients aged 40 years or older with COPD, stable cardiovascular function, and hyperinflation (residual volume > 135% predicted). Dynamic MRI data of these patients were retrospectively analyzed using the PREFUL technique to assess the effect of 14-day IND-GLY treatment versus placebo on regional measurements of ventilation dynamics. After manual segmentation of the lung parenchyma, flow-volume loops of each voxel were correlated to an individualized reference flow-volume loop, creating a two-dimensional flow-volume loop correlation map (FVL-CM) as a measure of ventilation dynamics. Ventilation-perfusion match (VQM) was evaluated in combination with perfusion and regional ventilation (VQMRVent) and with perfusion and the FVL-CM measurement (VQMCM). For image and statistical analysis, the lung parenchyma was segmented as a region of interest by manually delineating the lung boundary and excluding the large (central) vessels for each section. Differences in ventilation, perfusion, and VQM between IND-GLY and placebo were compared using analysis of variance, with study treatment, patient, and period included as factors.ResultsFifty patients (mean age, 64.3 years ± 7.65 [SD]; 35 men) were included in this analysis. IND-GLY significantly increased mean correlation as measured with FVL-CM versus that of placebo (least squares [LS] means treatment difference: 0.05 [95% CI: 0.03, 0.07]; P < .0001). Compared with placebo, IND-GLY increased mean Q (LS means treatment difference: 9.27 mL/min/100 mL [95% CI: 0.05, 18.49]; P = .049) and improved both VQMCM and VQMRVent (LS means treatment difference: 0.06 [95% CI: 0.03, 0.08]; P < .0001 and 0.05 [95% CI: 0.02, 0.08]; P = .001, respectively).ConclusionRegional ventilation dynamics and VQM measured by PREFUL MRI show treatment response in COPD. Supplemental material is available for this article. Clinical trial registration no. NTR6831Keywords: MRI, COPD, Perfusion, Ventilation, Lung, PulmonaryPublished under a CC BY 4.0 license

Defect distribution index: A novel metric for functional lung MRI in cystic fibrosis.

PurposeLung impairment from functional MRI is frequently assessed as defect percentage. The defect distribution, however, is currently not quantified. The purpose of this work was to develop a novel measure that quantifies how clustered or scattered defects in functional lung MRI appear, and to evaluate it in pediatric cystic fibrosis.TheoryThe defect distribution index (DDI) calculates a score for each lung voxel categorized as defected. The index increases according to how densely and how far an expanding circle around a defect voxel contains more than 50% defect voxels.MethodsFractional ventilation and perfusion maps of 53 children with cystic fibrosis were previously acquired with matrix pencil decomposition MRI. In this work, the DDI is compared to a visual score of 3 raters who evaluated how clustered the lung defects appear. Further, spearman correlations between DDI and lung function parameters were determined.ResultsThe DDI strongly correlates with the visual scoring (r = 0.90 for ventilation; r = 0.88 for perfusion; P < .0001). Although correlations between DDI and defect percentage are moderate to strong (r = 0.61 for ventilation; r = 0.75 for perfusion; P < .0001), the DDI distinguishes between patients with comparable defect percentage.ConclusionThe DDI is a novel measure for functional lung MRI. It provides complementary information to the defect percentage because the DDI assesses defect distribution rather than defect size. The DDI is applicable to matrix pencil MRI data of cystic fibrosis patients and shows very good agreement with human perception of defect distributions.

Perfusion quantification using voxel-wise proton density and median signal decay in PREFUL MRI.

Contrast-free lung MRI based on Fourier decomposition is an attractive method to monitor various lung diseases. However, the accuracy of the current perfusion quantification is limited. In this study, a new approach for perfusion quantification based on voxel-wise proton density and median signal decay toward the steady state for Fourier decomposition-based techniques is proposed called QQuantified (QQuant ). Twenty patients with chronic obstructive pulmonary disease and 18 patients with chronic thromboembolic pulmonary hypertension received phase-resolved functional lung-MRI (PREFUL) and dynamic contrast-enhanced (DCE)-MRI. Nine healthy participants received phase-resolved functional lung-MRI only. Median values of QQuant were compared to a Fourier decomposition perfusion quantification presented by Kjørstad et al (QKjørstad ) and validated toward pulmonary blood flow derived by DCE-MRI (PBFDCE ). Blood fraction maps determined by the new approach were calculated. Regional and global correlation coefficients were calculated, and Bland-Altman plots were created. Histogram analyses of all cohorts were created. The introduced parameter QQuant showed only 2 mL/min/100 mL mean deviation to PBFDCE in the patient cohort and showed less bias than QKjørstad . Significant increases of regional correlation with PBFDCE were achieved (r = 0.3 vs. r = 0.2, P < .01*). The trend of global correlation toward PBFDCE is not uniform, showing higher values for QKjørstad in the chronic obstructive pulmonary disease cohort than for QQuant and vice versa in the chronic thromboembolic pulmonary hypertension cohort. In contrast to QKjørstad , QQuant perfusion maps indicate a physiologic dorsoventral gradient in supine position similar to PBFDCE with similar value distribution in the histograms. We proposed a new approach for perfusion quantification of phase-resolved functional lung measurements. The developed parameter QQuant reveals a higher accuracy compared to QKjørstad .

Non-contrast pulmonary perfusion MRI in patients with cystic fibrosis

PurposeThis study aimed to assess the feasibility of Self-gated Non–Contrast-Enhanced Functional Lung (SENCEFUL) MRI for detection of pulmonary perfusion deficits in patients with cystic fibrosis. MethodsTwenty patients with cystic fibrosis and 20 matched healthy controls underwent SENCEFUL-MRI at 1.5 T with reconstruction of perfusion and perfusion phase maps (i.e. comparable to pulse wave delays). Four blinded readers rated both types of maps separately followed by simultaneous assessment thereof. Perfusion phase data was plotted in histograms and a Peak-to-Offset ratio was calculated for comparison to subjective scoring and correlation (Spearman) to lung function parameters. Sensitivity, specificity and positive and negative predictive values were calculated for subjective scoring and Peak-to-Offset ratios. Intraclass correlation (ICC) was used to assess the interrater agreement. ResultsReaders attributed pathological ratings 2.2–3.5 times more frequently to the CF-group. The sensitivity with regard to a correct assignment to CF was similar between ratings (perfusion only vs. perfusions phase only vs. simultaneous assessment: 0.54−0.56), while specificity increased from 0.75 to 0.85 for simultaneous assessment. ICC was 0.77−0.84 for subjective scoring. ROC-analysis of Peak-to-Offset ratios on a mean per-subject basis revealed a sensitivity of 0.75 and specificity of 0.85 (PPV 0.83, NPV 0.77). Functional pulmonary parameters indicative of bronchial obstruction and Peak-to-Offset ratios showed positive correlation (FEV1: 0.77; FEF75: 0.76). ConclusionsSENCEFUL-MRI bears the potential for monitoring CF including disease-associated patterns of altered pulmonary perfusion. The proposed Peak-to-Offset ratio derived from pulmonary perfusion phase measurements could represent an objective future marker for perfusion impairment.