Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

Regional flow volume loop ventilation-weighted noncontrast-enhanced proton lung MRI in free breathing has emerged as a novel technique for assessment of regional lung ventilation, but has yet not been validated with 129 Xenon MRI (129 Xe-MRI), a direct visualization of ventilation in healthy volunteers, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD) patients. To compare regional ventilation and regional flow volume loops measured by noncontrast-enhanced ventilation-weighted phase-resolved functional lung MRI (PREFUL-MRI) with 129 Xe-MRI ventilation imaging and with lung function test parameters. Retrospective study. Twenty patients with COPD, eight patients with CF, and six healthy volunteers. PREFUL and 129 Xe-MRI gradient echo sequences were acquired at 1.5T. Coronal slices of PREFUL-MRI (free breathing) and 129 Xe-MRI (single breath-hold) were acquired on the same day, matched by their ventrodorsal position and coregistered for evaluation. Ventilation defect percentage (VDP) was calculated based on regional ventilation (RV), regional flow volume loops (RFVL), or 129 Xe-MRI with two different threshold methods. A combined VDP was calculated for RV and RFVL. Additionally, lung function testing was performed (such as the forced expiratory volume in 1 second [FEV1 ]) was used. The obtained parameters were compared using Wilcoxon tests, correlated using Spearman's correlation coefficient (r), and agreement between PREFUL and 129 Xe-MRI parameters was assessed using Bland-Altman analysis and Dice coefficients. VDP measured by PREFUL and 129 Xe were significantly correlated with both thresholding techniques (r = 0.62-0.69, P < 0.05 for all) and with lung function test parameters. Combined RV and RFVL PREFUL defect maps correlated with lung function testing (eg, with FEV1 r = -0.87 P < 0.05), and showed better regional agreement to 129 Xe-MRI ventilation defects (Dice coefficient defect 0.413) with significantly higher VDP values (10.2 ± 27.3, P = 0.04) than either PREFUL defect map alone. Combined RV and RFVL PREFUL defect maps likely increase sensitivity to mild airway obstruction with increased VDP values compared to 129 Xe-MRI, and correlate strongly with lung function test parameters. 3 TECHNICAL EFFICACY STAGE: 2.

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.

MEASURES OF VENTILATION DERIVED FROM RADIOGRAPH VELOCIMETRY CORRELATE WITH SPIROMETRY IN PATIENTS WITH COPD

A previous study has demonstrated the feasibility of 3D phase-resolved functional lung (PREFUL) MRI in healthy volunteers and patients with chronic pulmonary disease. Before clinical use, the repeatability of the ventilation parameters derived from 3D PREFUL MRI must be determined. To evaluate repeatability of 3D PREFUL and to compare with pulmonary functional lung testing (PFT). Prospective. Fifty-three healthy subjects and 13 patients with chronic obstructive pulmonary disease (COPD). A prototype 3D stack-of-stars spoiled-gradient-echo sequence at 1.5 T. Study participants underwent repeated MRI examination (median time interval between scans COPD/healthy subjects [interquartile range]: 7/0 days [6-8/0-0 days]) and one PFT carried out at the time of the baseline MRI. For 3D PREFUL, regional ventilation (RVent) and flow-volume loops were computed and rated by cross-correlation (CC). Also, ventilation time-to-peak (VTTP) was computed. Ventilation defect percentage (VDP) maps were obtained for RVent and CC. Repeatability of 3D PREFUL parameters was evaluated using Bland-Altman analysis, coefficient of variation (COV) and intraclass correlation coefficient (ICC). The relation between 3D PREFUL and PFT measures (forced expiratory volume in 1 second (FEV1 ) and forced vital capacity (FVC) was assessed using the Pearson correlation coefficient (r). In healthy subjects and COPD patients, no significant bias (all P range: 0.09-0.77) and a moderate to good repeatability of RVent, VTTP, and VDPRVent were found (COV range: 0.1%-18.2%, ICC range: 0.51-0.88). For CC and VDPCC moderate repeatability was found (COV range: 0.6%-43.6%, ICC: 0.38-0.60). CC, VDPRVent , and VDPCC showed a good correlation with FEV1 (all |r| > 0.58, all P < 0.05) and FEV1 /FVC ratio (all |r| > 0.62, all P < 0.05). 3D PREFUL provided a good repeatability of RVent, VTTP, and VDPRVent and moderate repeatability of CC and VDPCC in healthy volunteers and COPD patients, and correlated well with FEV1 and FEV1 /FVC. 2 TECHNICAL EFFICACY STAGE: 2.

Hyperinflation in chronic obstructive pulmonary disease (COPD) patients worsens on exertion/exercise when breathing frequency increases. Fast breathing, paced at 40 breaths per minute using a metronome (metronome-paced tachypnea, MPT), induces dynamic hyperinflation (DH) and can be performed during MRI. MPT in combination with phase-resolved functional lung (PREFUL) MRI can be used to assess stress-driven ventilation dynamics globally and regionally. A 90 s time series of one coronal slice centered to the trachea was acquired for PREFUL MRI during 60 s of resting tidal breathing (RTB) and 30 s of MPT at 40 breaths per minute in COPD patients and healthy volunteers. MPT detected DH in 12 out of 15 COPD patients and in 1 out of 15 healthy controls. During MPT, the global fractional ventilation decreased by 20% in healthy subjects (p = 0.01) and by 48% in COPD patients (p < 0.001). The end-expiratory lung area remained stable in healthy subjects and increased significantly by 7% in COPD patients over the course of MPT (p = 0.004). Younger, healthy volunteers adapted to increase breathing frequency by reducing tidal volume (global fractional ventilation), while older healthy volunteers showed less tidal volume reduction (p = 0.036). The MPT-induced change of regional ventilation homogeneity (flow volume loop cross-correlation, FVL-CCMPT/RTB) increased with age in healthy volunteers (p = 0.039) likely due to the development of compensatory dystelectasis in younger volunteers leading to reduced homogeneity during MPT. In the future, the MPT test during MR imaging may be used for COPD treatment analysis and disease monitoring.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension in Patients With Chronic Obstructive Pulmonary Disease: A Note of Caution.

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. 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. 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. 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.

To compare regional ventilation assessed by non-contrast enhanced ventilation-weighted phase-resolved functional lung (PREFUL)MRI with parametric response mapping (PRM) and with pulmonary function test (PFT) parameters in patients with chronic obstructive pulmonary disease (COPD). This study was a retrospective analysis of a single-center subset of the prospective COPD cohort COSYCONET. PREFULMRI coronal sections were obtained during free breathing at 1.5 T using a spoiled gradient echo sequence. PRM was derived from paired low-dose inspiratory and expiratory CT scans. Matched coronal slices of PREFUL and PRM were co-registered. PREFUL ventilation defect percentage (PREFUL-VDP), as well as functional small airway disease (PRMfSAD), emphysema (PRMemph), and their combined metric (PRMfSAD+emph), were calculated. Global comparisons employed Spearman's correlation coefficient (r) and Wilcoxon signed-rank tests. Spatial agreement was assessed using spatial overlap and the Dice coefficient. Fifty-one patients (median age 65 [58-70]) were included in this study. PREFUL-VDP strongly correlated with combined PRMfSAD+emph (r = 0.86. p < 0.001) and with PFT parameters (PREFUL-VDP vs FEV1, r = -0.75, p < 0.001). Correlations between PREFUL-VDP with PRMfSAD and PRMemph separately were weaker (r = 0.57 and r = 0.82, p < 0.001 for both). In concordance, the highest spatial congruence was observed between PREFUL-VDP and PRMfSAD+emph (spatial overlap: 0.60 [0.55-0.66], Dice coefficient for defects: 0.53 [0.28-0.62]), indicating that PREFUL-VDP does not distinguish between small airway disease and emphysema. PREFUL-VDP correlates most strongly with the PRM measurement of emphysema and functional small airways disease combined and is a promising noninvasive, radiation-free tool for quantifying regional ventilation in COPD. QuestionHow does regional ventilation in COPD, measured by PREFUL MRI, correspond to CT-based PRM metrics? FindingsPREFUL MRI's VDP showed strong correlation and the highest spatial agreement with the combined CT PRM metric representing emphysema and functional small airways disease. Clinical relevancePREFUL MRI offers a non-invasive, radiation-free method for assessing regional ventilation in COPD. Although PREFUL cannot distinguish emphysema from small airways disease, its strong correlation with CT PRM highlights its value for disease characterization and functional monitoring.

To comprehensively assess the impact of aging, cigarette smoking, and chronic obstructive pulmonary disease (COPD) on pulmonary physiology using 129Xe MR. A total of 90 subjects were categorized into four groups, including healthy young (HY, n = 20), age-matched control (AMC, n = 20), asymptomatic smokers (AS, n = 28), and COPD patients (n = 22). 129Xe MR was utilized to obtain pulmonary physiological parameters, including ventilation defect percent (VDP), alveolar sleeve depth (h), apparent diffusion coefficient (ADC), total septal wall thickness (d), and ratio of xenon signal from red blood cells and interstitial tissue/plasma (RBC/TP). Significant differences were found in the measured VDP (p = 0.035), h (p = 0.003), and RBC/TP (p = 0.003) between the HY and AMC groups. Compared with the AMC group, higher VDP (p = 0.020) and d (p = 0.048) were found in the AS group; higher VDP (p < 0.001), d (p < 0.001) and ADC (p < 0.001), and lower h (p < 0.001) and RBC/TP (p < 0.001) were found in the COPD group. Moreover, significant differences were also found in the measured VDP (p < 0.001), h (p < 0.001), ADC (p < 0.001), d (p = 0.008), and RBC/TP (p = 0.032) between the AS and COPD groups. Our findings indicate that pulmonary structure and functional changes caused by aging, cigarette smoking, and COPD are various, and show a progressive deterioration with the accumulation of these risk factors, including cigarette smoking and COPD. Pathophysiological changes can be difficult to comprehensively understand due to limitations in common techniques and multifactorial etiologies. 129Xe MRI can demonstrate structural and functional changes caused by several common factors and can be used to better understand patients' underlying pathology. Standard techniques for assessing pathophysiological lung function changes, spirometry, and chest CT come with limitations. 129Xe MR demonstrated progressive deterioration with accumulation of the investigated risk factors, without these limitations. 129Xe MR can assess lung changes related to these risk factors to stage and evaluate the etiology of the disease.

Perfusion-weighted noncontrast-enhanced proton lung MRI during free breathing is maturing as a novel technique for assessment of regional lung perfusion, but has not yet been validated in chronic obstructive pulmonary disease (COPD) patients. To compare pulmonary parenchymal perfusion assessed by noncontrast-enhanced perfusion-weighted phase-resolved functional lung (PREFUL)-MRI with lung perfusion determined with dynamic gadolinium-enhanced (DCE)-MRI and with lung function test parameters. Prospective. A single-center subset of the COPD cohort "COPD and SYstemic consequenzes-COmorbidities NETwork" (COSYCONET). Forty-seven patients with COPD (median age 66 [57-70] years) were studied. For PREFUL-MRI a spoiled gradient echo sequence and for DCE-MRI, a 3D time-resolved spoiled gradient echo sequence was used at 1.5T. PREFUL-MRI coronal slices were acquired in free breathing. DCE-MRI was performed in breath-hold with administration of 0.025 mmol/kg bodyweight of gadobutrol i.v. at a rate of 4 ml/s and pulmonary blood flow (PBF) maps were calculated. Slices of PREFUL and DCE-MRI were matched by their ventrodorsal position and corresponding slices were coregistered for evaluation. Perfusion defect percentages (QDP) were calculated for both methods. The obtained parameters were correlated using Spearman's correlation coefficient (r) and Bland-Altman plot analysis. PREFUL-QDP showed an absolute and spatial agreement with PBF-QDP on a global (39.3 (31.8-45.5)% vs. 44.7 (35.4-50.0)% with a spatial overlap of 62.2 (57.2-67.2)%)) as well as on a lobar level and correlated with lung function test parameters (PREFUL-QDP vs. FEV1 , r = -0.75, P < 0.0001). There was a systematic overestimation of PREFUL-QDP compared with PBF-QDP, mainly in the lower lobes, resulting in an overall overestimation for the whole lung with a mean difference of 5% (95% confidence interval [CI]: 3.0%; 7.0%; STD 6.8%). PREFUL-MRI is a promising noninvasive, radiation-free tool for quantification of regional perfusion in COPD patients. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1122-1132.

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.

Muscle dysfunction is a common complication and an important prognostic factor in chronic obstructive pulmonary disease (COPD). As therapeutic strategies are still needed to treat this complication, gaining more insight into the process that leads to skeletal muscle decline in COPD appears to be an important issue. This review focuses on mitochondrial involvement in limb skeletal muscle alterations (decreased muscle mass, strength, endurance and power and increased fatigue) in COPD. Mitochondria are the main source of energy for the cells; they are involved in production of reactive oxygen species and activate an important pathway that leads to apoptosis. In COPD patients, skeletal muscles are characterized by decreased mitochondrial density and biogenesis, impaired activity and coupling of mitochondrial respiratory chain complexes, increased mitochondrial production of reactive oxygen species and, possibly, increased apoptosis. Of particular interest, a sedentary lifestyle, hypoxia, hypercapnia, tobacco smoking, corticosteroid therapy and, possibly, inflammation participate in this mitochondrial dysfunction, which is accessible to conventional therapies, such as exercise and tobacco cessation, as well as, potentially, to more innovative approaches, such as antioxidant treatment and supplementation with polyunsaturated fatty acids.

Ventilation heterogeneity is a hallmark finding in obstructive lung disease and may be evaluated using a variety of methods, including multiple-breath gas washout and pulmonary imaging. Such methods provide an opportunity to better understand the relationships between structural and functional abnormalities in the lungs, and their relationships with important clinical outcomes. We measured ventilation heterogeneity and respiratory impedance in 100 subjects [50 patients with asthma, 22 ex-smokers, and 28 patients with chronic obstructive pulmonary disease (COPD)] using oscillometry and hyperpolarized 3He magnetic resonance imaging (MRI) and determined their relationships with quality of life scores and disease control/exacerbations. We also coregistered MRI ventilation maps to a computational airway tree model to generate patient-specific respiratory impedance predictions for comparison with experimental measurements. In COPD and asthma patients, respectively, forced oscillation technique (FOT)-derived peripheral resistance (5-19 Hz) and MRI ventilation defect percentage (VDP) were significantly related to quality of life (FOT: COPD ρ = 0.4, P = 0.004; asthma ρ = -0.3, P = 0.04; VDP: COPD ρ = 0.6, P = 0.003; asthma ρ = -0.3, P = 0.04). Patients with poorly controlled asthma (Asthmatic Control Questionnaire >2) had significantly increased resistance (5 Hz: P = 0.01; 5-19 Hz: P = 0.006) and reactance (5 Hz: P = 0.03). FOT-derived peripheral resistance (5-19 Hz) was significantly related to VDP in patients with asthma and COPD patients (asthma: ρ = 0.5, P < 0.001; COPD: ρ = 0.5, P = 0.01), whereas total respiratory impedance was related to VDP only in patients with asthma (resistance 5 Hz: ρ = 0.3, P = 0.02; reactance 5 Hz: ρ = -0.5, P < 0.001). Model-predicted and FOT-measured reactance (5 Hz) were correlated in patients with asthma (ρ = 0.5, P = 0.001), whereas in COPD patients, model-predicted and FOT-measured resistance (5-19 Hz) were correlated (ρ = 0.5, P = 0.004). In summary, in patients with asthma and COPD patients, we observed significant, independent relationships for FOT-measured impedance and MRI ventilation heterogeneity measurements with one another and with quality of life scores. NEW & NOTEWORTHY In 100 patients, including patients with asthma and ex-smokers, 3He MRI ventilation heterogeneity and respiratory system impedance were correlated and both were independently related to quality of life scores and asthma control. These findings demonstrated the critical relationships between respiratory system impedance and ventilation heterogeneity and their role in determining quality of life and disease control. These observations underscore the dominant role that abnormalities in the lung periphery play in ventilation heterogeneity that results in patients' symptoms.

Free-breathing phase-resolved functional lung (PREFUL)-MRI may be useful for treatment monitoring in chronic obstructive pulmonary disease (COPD) patients with dyspnea. PREFUL test-retest reliability is essential for clinical application. To measure the repeatability of PREFUL-MRI ventilation (V) and perfusion (Q) parameters. Retrospective and prospective. A total of 28 COPD patients and 57 healthy subjects. 1.5T MRI/2D spoiled gradient echo imaging. V and Q lung parameter maps based on three coronal slices were obtained at baseline and after 14 days (COPD patients) or after a short pause outside the scanner (healthy subjects). Regional ventilation (RVent) and imaging flow volume loops by cross-correlation (ccVent) were quantified. Q was normalized to the signal of the main pulmonary artery (QN ) and quantified (QQuant ). Pulmonary pulse wave transit time (pPTT), voxel-by-voxel (regional), and whole lung (global) ventilation defect percentage based on RVent (VDPRVent ) and ccVent (VDPccVent ), perfusion defect percentage (QDP), and ventilation/perfusion match based on RVent (VQMRVent ) and ccVent (VQMccVent ) were calculated. Regional V and Q were analyzed globally for each subject. Each parameter's median of scans 1 and 2 were assessed by Wilcoxon sign rank test. A parameter's repeatability was analyzed by Bland-Altman analyses, coefficients of variation, intraclass correlation coefficients (ICC), and power calculations. The regional voxel repeatability was examined by calculating the Sørensen-Dice coefficient. There was no bias and no significant differences between the first and second MRI for any parameters (P > 0.05). Coefficient of variation ranged from 2.26% (ccVent) to 19.31% (QDP), ICC from 0.93 (QDP) to 0.60 (pPTT), the smallest detectable difference was 0.002 ccVent. Regional comparison showed the highest overlap (84%) in VDPRVent in healthy voxels and the lowest (53%) in VDPccVent defect voxels. V and Q PREFUL-MRI parameters were repeatable over two scan sessions in both healthy controls and COPD patients. 2 TECHNICAL EFFICACY STAGE: 2.

The purpose of this study is to evaluate whether accelerated registration and reduced acquisition times preserve the robustness of phase-resolved functional lung (PREFUL) MRI, thereby improving clinical feasibility by facilitating integration into tight time slots and enabling faster turnaround of results. PREFUL MRI at 1.5 T was retrospectively analyzed in 28 patients with chronic obstructive pulmonary disease (COPD) and 56 healthy volunteers. Image registration was performed using Advanced Normalization Tools (ANTs) and Forsberg. Time series (TS) were truncated from 55 to 45, 30, and 15 s per slice. The 55-s variant was evaluated twice to assess potential nondeterministic effects; the first served as the reference. PREFUL parameters, including regional ventilation, quantified perfusion (QQ), flow volume loop correlation metric (FVL-CM) and corresponding defect percentages, were compared across registration methods and TS lengths using Wilcoxon tests, Pearson correlations, intraclass correlation coefficients (ICC), and regional overlap analysis. Forsberg reduced computation time by ~20-fold (3 vs. 58 min per slice) while maintaining trends and repeatability. Although functional values were slightly lower and defect scores higher, correlations between registrations exceeded 90% for most parameters, with regional overlap ≥ 97% in healthy volunteers and ≥ 80% in COPD patients. Shortening the TS to 30 s introduced minor deviations but preserved overlap (≥ 79%) and strong correlations (≥ 77%) compared with 55 s, except for QQ. Larger deviations occurred primarily at 15 s. Repeatability remained moderate to high (ICC ≥ 68%) for all parameters, except QQ, down to 30 s, with the FVL-CM, perfusion defect percentage and amount of nondefect regions in COPD being most stable (ICC ≥ 72%). Forsberg provides results comparable to ANTs at a fraction of the processing time, enabling PREFUL analysis within a practical timeframe. Acquisition for each slice may be reduced to 30 s without compromising robustness, supporting more efficient protocols, although caution is warranted for QQ.