Doppler-derived pulmonary pulse transit time measurements in chronic obstructive pulmonary disease: Reproducibility and cardiopulmonary function.

INTRODUCTION: Doppler-derived pulmonary pulse transit time (pPTT) is an auspicious hemodynamic marker in chronic pulmonary diseases. The aim is to compare four distinct pPTT measurements and its relation to right cardiac and pulmonary function. METHODS: Prospectively, 25 chronic obstructive pulmonary disease (COPD) patients (four patients excluded) and 32 healthy subjects underwent repeated distinct pPTT measurements, standard echocardiography, and pulmonary function testing on the same day. pPTT was defined as the interval from the R or Q-wave in the electrocardiogram to the corresponding pulse wave Doppler peak late systolic (S) 2 or diastolic (D) pulmonary vein flow velocity (pPTT R-S, Q-S, R-D, Q-D). Reproducibility was assessed using Bland-Altman analysis, coefficient of variation (COV), intraclass correlation coefficient (ICC), and power calculations. Associations with right ventricular RV tissue and pulse wave Doppler velocities (RV E', RV S', RV A', RV E, RV A, RV E/E', RV E/A), TAPSE, right ventricular fractional area change, left ventricular systolic and diastolic function (LV ejection fraction, E, A, E/A, E/E', septal E', lateral E'), LA diameters, as well as forced expiratory volume in 1 s, forced vital capacity (FVC) predicted (%), and in liters were analyzed. RESULTS: There was no significant difference and no bias between pPTT measures (p range: .1-.9). COV was in COPD 1.2%-2.3%, in healthy subjects 1.0%-3.1%. ICC ranged from .92 (COPD) to .96 (healthy subjects). In COPD significant correlations were found for pPTT R-S, Q-S and R-D with RV E`, (all > ρ: .49, < p = .0364), pPTT R-S, Q-S with RV E/E` (both > ρ: .49, < p = .0291), pPTT Q-S with RV S´ (ρ: .58, p = .0134), RV A (ρ: .59, p = .0339) and heart rate > ρ: -.39, < p = .0297). pPTT R-S, R-D showed significant correlations with FVC predicted (%) (ρ: .48 p = .0224) and FVC (l) (ρ:.47 p = .0347). CONCLUSIONS: All pPTT measures exhibited high reproducibility. In COPD patients pPTT measures correlate with diastolic right ventricular function. Defining Q as starting point seems clinically advantageous considering electromechanical desynchrony in patients with conduction disorders.

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.

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.

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.

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.

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.

Evaluation of image registration algorithms for 3D phase-resolved functional lung ventilation magnetic resonance imaging in healthy volunteers and chronic obstructive pulmonary disease patients.

The purpose of the current study was to assess the influence of the registration algorithms on the repeatability of three-dimensional (3D) phase-resolved functional lung (PREFUL) ventilation magnetic resonance imaging (MRI). Twenty-three healthy volunteers and 10 patients with chronic obstructive pulmonary disease (COPD) underwent 3D PREFUL MRI during tidal breathing. The registration of dynamically acquired data to a fixed image was executed using single-step, stepwise, and group-oriented registration (GOREG) approaches. Advanced Normalization Tools (ANTs) and the Forsberg image-registration package were used for the registration. Image registration algorithms were tested for differences and evaluated by the repeatability analysis of ventilation parameters using coefficient of variation (CoV), intraclass-correlation coefficient, Bland-Altman plots, and correlation to spirometry. Also, the registration time and image quality were computed for all registration approaches. Very strong to strong correlations (r range: 0.917-0.999) were observed between ventilation parameters derived using various registration approaches. Median CoV values of the cross-correlation (CC) parameter were significantly lower (all p ≤ 0.0054) for ANTs GOREG compared with single-step and stepwise ANTs registration. The majority of comparisons between COPD patients and age-matched healthy volunteers showed agreement among the registration approaches. The repeatability of regional ventilation (RVent)-based ventilation defect percentage (VDPRVent ) and VDPCC was significantly higher (both p ≤ 0.0054) for Forsberg GOREG compared with ANTs GOREG. All 3D PREFUL-derived ventilation parameters correlated with forced expiratory volume in 1 s (FEV1 ) and the FEV1 / forced vital capacity (FVC) ratio (all |r| > 0.40, all p < 0.03). The image sharpness of RVent maps was statistically elevated (all p < 0.001) using GOREG compared with single-step and stepwise registration approaches using ANTs. The best computational performance was achieved with Forsberg GOREG. The GOREG scheme improves the repeatability and image quality of dynamic 3D PREFUL ventilation parameters. Registration time can be ~10-fold reduced to 9 min using the Forsberg method with equal or even improved repeatability and comparable PREFUL ventilation results compared with the ANTs method.

Feasibility of flow-related enhancement brain perfusion MRI.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Evaluation of tissue shrinkage after CT-guided microwave ablation in patients with liver malignancies using Jacobian determinant.

PURPOSE: To assess short-term tissue shrinkage in patients with liver malignancies undergoing computed tomography (CT)-guided microwave ablation (MWA) using Jacobian determinant (JD). MATERIALS AND METHODS: Twenty-nine patients with 29 hepatic malignancies (primary n = 24; metastases n = 5; median tumor diameter 18 mm) referred to CT-guided MWA (single position; 10 min, 100 W) were included in this retrospective IRB-approved study, after exclusion of five patients. Following segmentation of livers and tumors on pre-interventional images, segmentations were registered on post-interventional images. JD mapping was applied to quantify voxelwise tissue volume changes after MWA. Percentual volume changes were evaluated in the ablated tumor, a 5-cm tumor perimeter and in the whole liver and compared in different clinical conditions (tumor entity: primary vs. secondary; tumor location: subcapsular vs. non-subcapsular; tumor volume: >/<6 ml: cirrhosis: yes vs. no; prior chemotherapy: yes vs. no using Shapiro-Wilk, χ2 and Wilcoxon rank sum tests, respectively (with p < 0.05 deemed significant). RESULTS: Tissue volume change was 0.6% in the ablated tumor, 1.6% in the 5-cm perimeter and 0.3% in the whole liver. Shrinkage in the ablated tumor was pronounced in non-subcapsular located tumors, whereas tissue expansion was noted in subcapsular tumors (median -3.5 vs. 1.1%; p = 0.0195). Shrinkage in the whole liver was higher in tumor volumes >6ml, compared with smaller tumors, in which tissue expansion was noted (median -1.0 vs. 2.5%; p = 0.002). Other clinical conditions had no significant influence on the extent of tissue shrinkage (p > 0.05). CONCLUSION: 3D Jacobian analysis shows that hepatic tissue deformation following MWA is most pronounced in a 5-cm area surrounding the treated tumor. Tumor location and tumor volume may have an impact on the extent of tissue shrinkage which may affect estimation of the safety margin.

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

For sensitive diagnosis and monitoring of pulmonary disease, ionizing radiation-free imaging methods are of great importance. A noncontrast and free-breathing proton magnetic resonance imaging (MRI) technique for assessment of pulmonary perfusion is phase-resolved functional lung (PREFUL) MRI. Since there is no validation of PREFUL MRI across different centers and scanners, the purpose of this study was to compare perfusion-weighted PREFUL MRI with the well-established dynamic contrast-enhanced (DCE) MRI across two centers on scanners from two different vendors. Sixteen patients with cystic fibrosis (CF) (Center 1: 10 patients; Center 2: 6 patients) underwent PREFUL and DCE MRI at 1.5T in the same imaging session. Normalized perfusion-weighted values and perfusion defect percentage (QDP) values were calculated for the whole lung and three central slices (dorsal, central, ventral of the carina). Obtained parameters were compared using Pearson correlation, Spearman correlation, Bland-Altman analysis, Wilcoxon signed-rank test, and Wilcoxon rank-sum test. Moderate-to-strong correlations between normalized perfusion-weighted PREFUL and DCE values were found (posterior slice: r = 0.69, p < 0.01). Spatial overlap of PREFUL and DCE QDP maps showed an agreement of 79.4% for the whole lung. Further, spatial overlap values of Center 1 were not significantly different to those of Center 2 for the three central slices (p > 0.07). The feasibility of PREFUL MRI across two different centers and two different vendors was shown in patients with CF and obtained results were in agreement with DCE MRI.

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

Purpose: To 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 Methods: The 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. Results: Fifty 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). Conclusion: Regional 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.

Validation of Phase-Resolved Functional Lung (PREFUL) Magnetic Resonance Imaging Pulse Wave Transit Time Compared to Echocardiography in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) pulmonary pulse wave transit time (pPTT) is a contrast agent free, vascular imaging biomarker, but has not been validated in chronic obstructive pulmonary disease (COPD). PURPOSE: To validate PREFUL with echocardiographic pPTT as a reference standard and to compare arterial/venous pPTT mapping with spirometry and clinical parameters. STUDY TYPE: Prospective. POPULATION: Twenty-one patients (62% female) with COPD and 44 healthy participants (50% female). FIELD STRENGTH/SEQUENCE: 1.5 T; 2D-spoiled gradient-echo sequence. ASSESSMENT: Three coronal PREFUL MRI slices, echocardiography, and spirometry including forced expiratory volume in 1 second (FEV1, liter) and predicted defined as FEV1 in% divided by the population average FEV1%, were performed. Pulmonary pulse transit time from the main artery to the microvasculature (PREFUL pPTT), to the right upper lobe vein (PREFUL pPTTav , echo pPTTav ), from microvasculature to right upper lobe vein (PREFULvein ) and the ratio of PREFUL pPTT to PREFUL pPTTvein were calculated. Body mass index (BMI), Global Initiative for COPD (GOLD) stage 1-4, disease duration, and cigarette packs smoked per day multiplied by the smoked years (pack years) were computed. STATISTICAL TESTS: Shapiro-Wilk-test, paired-two-sided-t-tests, Bland-Altman-analysis, coefficient of variation, Pearson ρ were applied, pPTT data were compared between 21 subjects from the 44 healthy subjects who were age- and sex-matched to the COPD cohort, P < 0.05 was considered statistically significant. RESULTS: PREFUL pPTTav significantly correlated with echo pPTTav (ρ = 0.95) with 1.85 msec bias, 95% limits of agreement: 55.94 msec, -52.23 msec in all participants (P = 0.59). In the healthy participants, PREFUL and echo pPTTav significantly correlated with age (ρ = 0.81, ρ = 0.78), FEV1 (ρ = -0.47, ρ = -0.34) and BMI (ρ = 0.56, ρ = 0.51). In COPD patients, PREFUL pPTT significantly correlated with FEV1 predicted (ρ = -0.59), GOLD (ρ = 0.53), disease duration (ρ = 0.54), and pack years (ρ = 0.49). DATA CONCLUSION: Arteriovenous PTT measured by PREFUL MRI corresponds precisely to echocardiography and appears to be feasible even in severe COPD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

High resolution flat-panel CT arthrography vs. MR arthrography of artificially created osteochondral defects in ex vivo upper ankle joints.

PURPOSE: High resolution flat-panel computed tomography arthrography (FPCT-A) and magnetic resonance arthrography (MR-A) are well suited to evaluate osteochondral lesions. The current study compares the performance of FPCT-A versus MR-A in an experimental setting. METHODS: Fourteen cadaveric ankles were prepared with artificial osteochondral defects of various sizes in four separate talar locations. After intra-articular contrast injection, FPCT-A and 3-T MR-A were acquired. Each defect was then filled with synthetic pallets. The resulting cast was used as reference. Two independent radiologists measured the dimensions of all defects with FPCT-A and MR-A. Intra-class correlation coefficients (ICC) were calculated. Data were compared using t-tests and Bland-Altman plots. RESULTS: The correlation for FPCT-A and cast was higher compared to MR-A and cast (ICC 0.876 vs. 0.799 for surface [length x width]; ICC 0.887 vs. 0.866 for depth, p<0.001). Mean differences between FPCT-A and cast measurements were -1.1 mm for length (p<0.001), -0.7 mm for width (p<0.001) and -0.4 mm for depth (p = 0.023). By MR-A, there were no significant differences for length and width compared to cast (p>0.05). Depth measurements were significantly smaller by MR-A (mean difference -1.1 mm, p<0.001). There was no bias between the different modalities. CONCLUSIONS: Ex vivo FPCT-A and MR-A both deliver high diagnostic accuracy for the evaluation of osteochondral defects. FPCT-A was slightly more accurate than MR-A, which was most significant when measuring lesion depth.

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

PURPOSE: 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 ). METHODS: 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. RESULTS: 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. CONCLUSION: 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 .