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

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

4DCT ventilation function image-based functional lung protection for esophageal cancer radiotherapy.

BACKGROUND: 4DCT (four-dimensional computed tomography) can effectively obtain functional lung ventilation images for patients and integrate them into radiotherapy treatment planning. Studies have not been performed on esophageal cancer, and there is no clear consensus on the optimal functional lung threshold for functional lung. METHODS: Functional lung images were generated for 11 patients with esophageal cancer. The correlation between the dose-volume parameters of functional lung (FL) as defined by different thresholds and the change of PFT/PDFT (pulmonary [diffusion] function test) metrics before and after radiotherapy were evaluated. FL-sparing planning was generated for each patient to preserve the functional lung and compared to conventional anatomical CT (non-sparing) planning. RESULTS: There was a significant positive correlation between the FL0.8 (defined Jacobian value ≤ 0.8), FL0.84, and FL0.9 dose-volume parameters and ΔFEV1/FVC (reduction before and after radiotherapy), and the FL0.8­V30 correlation was the strongest (r = 0.819, P < 0.01). The FL-sparing planning had a target area conformity index and homogeneity index comparable to the non-sparing planning (P > 0.05). For FL, the FL-sparing planning achieved lower FL-MLD (6.30 ±â€¯2.14 Gy vs. 7.83 ± 2.70 Gy), V10 (17.13 ±â€¯7.70% vs. 27.40 ± 9.48%), and V20 (6.96 ±â€¯3.85% vs. 11.63 ± 7.19%) compared to the non-sparing planning (P < 0.05), while heart and spinal cord doses were not significantly different between the two planning groups. CONCLUSION: The 4DCT-based FL irradiation dose for esophageal cancer was significantly associated with a decrease in FEV1/FVC. The optimal FL defined as a Jacobian value ≤ 0.8 or about 21% of the whole lung volume may be a good choice. FL-sparing planning significantly reduced the FL dose without compromising target area coverage.

Quantifying ventilation by X-ray velocimetry in healthy adults.

RATIONALE: X-ray velocimetry (XV) has been utilized in preclinical models to assess lung motion and regional ventilation, though no studies have compared XV-derived physiologic parameters to measures derived through conventional means. OBJECTIVES: To assess agreement between XV-analysis of fluoroscopic lung images and pitot tube flowmeter measures of ventilation. METHODS: XV- and pitot tube-derived ventilatory parameters were compared during tidal breathing and with bilevel-assisted breathing. Levels of agreement were assessed using the Bland-Altman analysis. Mixed models were used to characterize the association between XV- and pitot tube-derived values and optimize XV-derived values for higher ventilatory volumes. MEASUREMENTS AND MAIN RESULTS: Twenty-four healthy volunteers were assessed during tidal breathing and 11 were reassessed with increased minute ventilation with bilevel-assisted breathing. No clinically significant differences were observed between the two methods for respiratory rate (average Δ: 0.58; 95% limits of agreement: -1.55, 2.71) or duty cycle (average Δ: 0.02; 95% limits of agreement: 0.01, 0.03). Tidal volumes and flow rates measured using XV were lower than those measured using the pitot tube flowmeter, particularly at the higher volume ranges with bilevel-assisted breathing. Under these conditions, a mixed-model based adjustment was applied to the XV-derived values of tidal volume and flow rate to obtain closer agreement with the pitot tube-derived values. CONCLUSION: Radiographically obtained measures of ventilation with XV demonstrate a high degree of correlation with parameters of ventilation. If the accuracy of XV were also confirmed for assessing the regional distribution of ventilation, it would provide information that goes beyond the scope of conventional pulmonary function tests or static radiographic assessments.

Comparison between functional lung volume measurement and segment counting for predicting postoperative pulmonary function after pulmonary resection in lung cancer patients.

BACKGROUND: Functional lung volume (FLV) obtained from computed tomography images was a breakthrough for lung imaging and functional assessment. We compared the accuracy of the FLV measurement method and the segment-counting (SC) method in predicting postoperative pulmonary function. METHODS: A total of 113 patients who underwent two thoracoscopic surgeries were enrolled in our study. We predicted postoperative pulmonary function by the FLV measurement method and the SC method. Novel formulas based on the FLV measurement method were established using linear regression equations between the factors affecting pulmonary function and the measured values. RESULTS: The predicted postoperative forced vital capacity (ppoFVC) and forced expiratory volume in 1 s (ppoFEV1) measured by the 2 methods showed high concordance between the actual postoperative forced vital capacity (postFVC) and the forced expiratory volume in 1 s (postFEV1) [r = 0.762, P < 0.001 (FLV method) and r = 0.759, P < 0.001 (SC method) for FVC; r = 0.790, P < 0.001 (FLV method) and r = 0.795, P < 0.001 (SC method) for FEV1]. Regression analysis showed that the measured preoperative pulmonary function parameters (FVC, FEV1) and the ratio of reduced FLV to preoperative FLV were significantly associated with the actual postoperative values and could predict these parameters (all P < 0.001). The feasibility of using these equations [postFVC = 0.8 × FVC - 0.784 × ΔFLV/FLV + 0.283 (R2 = 0.677, RSD = 0.338), postFEV1 = 0.766 × FEV1 - 0.694 × ΔFLV/FLV + 0.22 (R2 = 0.743, RSD = 0.265)] to predict the pulmonary function parameters after wedge resection was also verified. CONCLUSIONS: The new FLV measurement method is valuable for predicting postoperative pulmonary function in patients undergoing lung resection surgery, with accuracy and consistency similar to those of the conventional SC method.

Assessment of lung ventilation of premature infants with bronchopulmonary dysplasia at 1.5 Tesla using phase-resolved functional lung magnetic resonance imaging.

BACKGROUND: The most common chronic complication of preterm birth is bronchopulmonary dysplasia (BPD), widely referred to as chronic lung disease of prematurity. All current definitions rely on characterizing the disease based on respiratory support level and do not provide full understanding of the underlying cardiopulmonary pathophysiology. OBJECTIVE: To evaluate a rapid functional lung imaging technique in premature infants and to quantitate pulmonary ventilation using 1.5 Tesla magnetic resonance imaging (MRI). MATERIALS AND METHODS: We conducted a prospective MRI study of 12 premature infants in the neonatal intensive care unit (NICU) using the phase resolved functional lung MRI technique to calculate pulmonary ventilation parameters in preterm infants with and without BPD grade 0/1 (n = 6) and grade 2/3 (n = 6). RESULTS: The total ventilation defect percentage showed a significant difference between groups (16.0% IQR (11.0%,18%) BPD grade 2/3 vs. 8.0% IQR (4.5%,9.0%) BPD grade 0/1, p = 0.01). CONCLUSION: Phase-resolved functional lung MRI is feasible for assessment of ventilation defect percentages in preterm infants and shows regional variation in localized lung function in this population.

Preclinical Four-Dimensional Functional Lung Imaging and Quantification of Regional Airflow: A New Standard in Lung Function Evaluation in Murine Models.

The current standard for lung function evaluation in murine models is based on forced oscillation technology, which provides a measure of the total airway function but cannot provide information on regional heterogeneity in function. Limited detection of regional airflow may contribute to a discontinuity between airway inflammation and airflow obstruction in models of asthma. Here, we describe quantification of regional airway function using novel dynamic quantitative imaging and analysis to quantify and visualize lung motion and regional pulmonary airflow in four dimensions (4D). Furthermore, temporo-spatial specific ventilation (ml/ml) is used to determine ventilation heterogeneity indices for lobar and sublobar regions, which are directly compared to ex vivo biological analyses in the same sublobar regions. In contrast, oscillation-based technology in murine genetic models of asthma have failed to demonstrate lung function change despite altered inflammation, whereas 4D functional lung imaging demonstrated diminished regional lung function in genetic models relative to wild-type mice. Quantitative functional lung imaging assists in localizing the regional effects of airflow. Our approach reveals repeatable and consistent differences in regional airflow between lung lobes in all models of asthma, suggesting that asthma is characterized by regional airway dysfunctions that are often not detectable in composite measures of lung function. 4D functional lung imaging technology has the potential to transform discovery and development in murine models by mapping out regional areas heterogeneously affected by the disease, thus deciphering pathobiology with greater precision.

Abnormal dynamic ventilation function of COVID-19 survivors detected by pulmonary free-breathing proton MRI.

OBJECTIVES: To visualize and quantitatively assess regional lung function of survivors of COVID-19 who were hospitalized using pulmonary free-breathing 1H MRI. METHODS: A total of 12 healthy volunteers and 27 COVID-19 survivors (62.4 ± 8.1 days between infection and image acquisition) were recruited in this prospective study and performed chest 1H MRI acquisitions with free tidal breathing. Then, conventional Fourier decomposition ventilation (FD-V) and global fractional ventilation (FVGlobal) were analyzed. Besides, a modified PREFUL (mPREFUL) method was developed to adapt to COVID-19 survivors and generate dynamic ventilation maps and parameters. All the ventilation maps and parameters were analyzed using Student's t-test. Pearson's correlation and a Bland-Altman plot between FVGlobal and mPREFUL were analyzed. RESULTS: There was no significant difference between COVID-19 and healthy groups regarding a static FD-V map (0.47 ± 0.12 vs 0.42 ± 0.08; p = .233). However, mPREFUL demonstrated lots of regional high ventilation areas (high ventilation percentage (HVP): 23.7% ± 10.6%) existed in survivors. This regional heterogeneity (i.e., HVP) in survivors was significantly higher than in healthy volunteers (p = .003). The survivors breathed deeper (flow-volume loop: 5375 ± 3978 vs 1688 ± 789; p = .005), and breathed more air in respiratory cycle (total amount: 62.6 ± 19.3 vs 37.3 ± 9.9; p < .001). Besides, mPREFUL showed both good Pearson's correlation (r = 0.74; p < .001) and Bland-Altman consistency (mean bias = -0.01) with FVGlobal. CONCLUSIONS: Dynamic ventilation imaging using pulmonary free-breathing 1H MRI found regional abnormity of dynamic ventilation function in COVID-19 survivors. KEY POINTS: • Pulmonary free-breathing1H MRI was used to visualize and quantitatively assess regional lung ventilation function of COVID-19 survivors. • Dynamic ventilation maps generated from 1H MRI were more sensitive to distinguish the COVID-19 and healthy groups (total air amount: 62.6 ± 19.3 vs 37.3 ± 9.9; p < .001), compared with static ventilation maps (FD-V value: 0.47 ± 0.12 vs 0.42 ± 0.08; p = .233). • COVID-19 survivors had larger regional heterogeneity (high ventilation percentage: 23.7% ± 10.6% vs 13.1% ± 7.9%; p = .003), and breathed deeper (flow-volume loop: 5375 ± 3978 vs 1688 ± 789; p = .005) than healthy volunteers.

Abnormal pulmonary perfusion heterogeneity in patients with Fontan circulation and pulmonary arterial hypertension.

KEY POINTS: The distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients. Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology. ABSTRACT: Many factors affect the distribution of pulmonary perfusion, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. An example is following the Fontan procedure, where pulmonary perfusion is passive, and heterogeneity may be increased because of the underlying pathophysiology leading to Fontan palliation, remodelling, or increased gravitational gradients from low flow. Another is pulmonary arterial hypertension (PAH), where gravitational gradients may be reduced secondary to high pressures, but remodelling may increase perfusion heterogeneity. We evaluated regional pulmonary perfusion in Fontan patients (n = 5), healthy young controls (Fontan control, n = 5), patients with PAH (n = 6) and healthy older controls (PAH control) using proton magnetic resonance imaging. Regional perfusion was measured using arterial spin labelling. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Mean perfusion was similar (Fontan = 2.50 ± 1.02 ml min-1  ml-1 ; Fontan control = 3.09 ± 0.58, PAH = 3.63 ± 1.95; PAH control = 3.98 ± 0.91, P = 0.26), and the slopes of gravitational gradients were not different (Fontan = -0.23 ± 0.09 ml min-1  ml-1  cm-1 ; Fontan control = -0.29 ± 0.23, PAH = -0.27 ± 0.09, PAH control = -0.25 ± 0.18, P = 0.91) between groups. Perfusion relative dispersion was greater in both Fontan and PAH than controls (Fontan = 1.46 ± 0.18; Fontan control = 0.99 ± 0.21, P = 0.005; PAH = 1.22 ± 0.27, PAH control = 0.91 ± 0.12, P = 0.02) but similar between patient groups (P = 0.13). These findings persisted after removing contributions from large blood vessels and gravitational gradients (all P < 0.05). We conclude that patients with Fontan physiology and PAH have increased pulmonary perfusion heterogeneity that is not explained by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects the effects of remodelling in PAH and possibly in Fontan physiology.

Image- versus histogram-based considerations in semantic segmentation of pulmonary hyperpolarized gas images.

PURPOSE: To characterize the differences between histogram-based and image-based algorithms for segmentation of hyperpolarized gas lung images. METHODS: Four previously published histogram-based segmentation algorithms (ie, linear binning, hierarchical k-means, fuzzy spatial c-means, and a Gaussian mixture model with a Markov random field prior) and an image-based convolutional neural network were used to segment 2 simulated data sets derived from a public (n = 29 subjects) and a retrospective collection (n = 51 subjects) of hyperpolarized 129Xe gas lung images transformed by common MRI artifacts (noise and nonlinear intensity distortion). The resulting ventilation-based segmentations were used to assess algorithmic performance and characterize optimization domain differences in terms of measurement bias and precision. RESULTS: Although facilitating computational processing and providing discriminating clinically relevant measures of interest, histogram-based segmentation methods discard important contextual spatial information and are consequently less robust in terms of measurement precision in the presence of common MRI artifacts relative to the image-based convolutional neural network. CONCLUSIONS: Direct optimization within the image domain using convolutional neural networks leverages spatial information, which mitigates problematic issues associated with histogram-based approaches and suggests a preferred future research direction. Further, the entire processing and evaluation framework, including the newly reported deep learning functionality, is available as open source through the well-known Advanced Normalization Tools ecosystem.

The impact of segmentation on whole-lung functional MRI quantification: Repeatability and reproducibility from multiple human observers and an artificial neural network.

PURPOSE: To investigate the repeatability and reproducibility of lung segmentation and their impact on the quantitative outcomes from functional pulmonary MRI. Additionally, to validate an artificial neural network (ANN) to accelerate whole-lung quantification. METHOD: Ten healthy children and 25 children with cystic fibrosis underwent matrix pencil decomposition MRI (MP-MRI). Impaired relative fractional ventilation (RFV ) and relative perfusion (RQ ) from MP-MRI were compared using whole-lung segmentation performed by a physician at two time-points (At1 and At2 ), by an MRI technician (B), and by an ANN (C). Repeatability and reproducibility were assess with Dice similarity coefficient (DSC), paired t-test and Intraclass-correlation coefficient (ICC). RESULTS: The repeatability within an observer (At1 vs At2 ) resulted in a DSC of 0.94 ± 0.01 (mean ± SD) and an unsystematic difference of -0.01% for RFV (P = .92) and +0.1% for RQ (P = .21). The reproducibility between human observers (At1 vs B) resulted in a DSC of 0.88 ± 0.02, and a systematic absolute difference of -0.81% (P < .001) for RFV and -0.38% (P = .037) for RQ . The reproducibility between human and the ANN (At1 vs C) resulted in a DSC of 0.89 ± 0.03 and a systematic absolute difference of -0.36% for RFV (P = .017) and -0.35% for RQ (P = .002). The ICC was >0.98 for all variables and comparisons. CONCLUSIONS: Despite high overall agreement, there were systematic differences in lung segmentation between observers. This needs to be considered for longitudinal studies and could be overcome by using an ANN, which performs as good as human observers and fully automatizes MP-MRI post-processing.

Repeatability of Phase-Resolved Functional Lung (PREFUL)-MRI Ventilation and Perfusion Parameters in Healthy Subjects and COPD Patients.

BACKGROUND: 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. PURPOSE: To measure the repeatability of PREFUL-MRI ventilation (V) and perfusion (Q) parameters. STUDY TYPE: Retrospective and prospective. POPULATION: A total of 28 COPD patients and 57 healthy subjects. FIELD STRENGTH/SEQUENCE: 1.5T MRI/2D spoiled gradient echo imaging. ASSESSMENT: 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. STATISTICAL TESTS: 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. RESULTS: 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. DATA CONCLUSION: V and Q PREFUL-MRI parameters were repeatable over two scan sessions in both healthy controls and COPD patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Echo Time-Dependent Observed Lung T1 in Patients With Chronic Obstructive Pulmonary Disease in Correlation With Quantitative Imaging and Clinical Indices.

BACKGROUND: There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T1 (T1 (TE)) depends on the echo-time (TE) and reflects regional pulmonary function. PURPOSE: To investigate the potential diagnostic value of T1 (TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT. STUDY TYPE: Prospective non-randomized diagnostic study. POPULATION: Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference. FIELD STRENGTH/SEQUENCE: Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for T1 (TE) mapping at TE1-5  = 70 µsec, 500 µsec, 1200 µsec, 1650 µsec, and 2300 µsec. ASSESSMENT: Perfusion images were scored by three radiologists. T1 (TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired. STATISTICAL TESTS: Spearman rank correlation coefficients (ρ) were calculated between T1 (TE) and perfusion scores, clinical parameters and qCT. A P-value <0.05 was considered statistically significant. RESULTS: Median values were T1 (TE1-5 ) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T1 was observed from TE1 to TE2 , with no changes from TE2 to TE3 (P = 0.48), TE3 to TE4 (P = 0.94) or TE4 to TE5 (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman's correlations between T1 and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ < 0.70), mean lung density (MLD, ρ < 0.72) and the perfusion score (ρ > -0.69) were found. Overall, correlations were strongest at TE2 , weaker at TE1 and rarely significant at TE4 -TE5 . DATA CONCLUSION: In COPD patients, the increase of T1 (TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T1 and clinical parameters of disease at longer TEs, this suggests that T1 (TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T1 (TE) mapping might be developed further to provide diagnostic information beyond T1 at a single TE. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Mechanical power during extracorporeal membrane oxygenation and hospital mortality in patients with acute respiratory distress syndrome.

BACKGROUND: Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. RESULTS: A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214-4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018-1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002-1.007], p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p < 0.001). CONCLUSIONS: MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.

Functional avoidance-based intensity modulated proton therapy with 4DCT derived ventilation imaging for lung cancer.

The primary objective is to evaluate the potential dosimetric gains of performing functional avoidance-based proton treatment planning using 4DCT derived ventilation imaging. 4DCT data of 31 patients from a prospective functional avoidance clinical trial were evaluated with intensity modulated proton therapy (IMPT) plans and compared with clinical volumetric modulated arc therapy (VMAT) plans. Dosimetric parameters were compared between standard and functional plans with IMPT and VMAT with one-way analysis of variance and post hoc paired student t-test. Normal Tissue Complication Probability (NTCP) models were employed to estimate the risk of two toxicity endpoints for healthy lung tissues. Dose degradation due to proton motion interplay effect was evaluated. Functional IMPT plans led to significant dose reduction to functional lung structures when compared with functional VMAT without significant dose increase to Organ at Risk (OAR) structures. When interplay effect is considered, no significant dose degradation was observed for the OARs or the clinical target volume (CTV) volumes for functional IMPT. Using fV20 as the dose metric and Grade 2+ pneumonitis as toxicity endpoint, there is a mean 5.7% reduction in Grade 2+ RP with the functional IMPT and as high as 26% in reduction for individual patient when compared to the standard IMPT planning. Functional IMPT was able to spare healthy lung tissue to avoid excess dose to normal structures while maintaining satisfying target coverage. NTCP calculation also shows that the risk of pulmonary complications can be further reduced with functional based IMPT.

Echo Time-Dependence of Observed Lung T1 in Patients With Cystic Fibrosis and Correlation With Clinical Metrics.

BACKGROUND: Noninvasive monitoring of early abnormalities and therapeutic intervention in cystic fibrosis (CF) lung disease using MRI is important. Lung T1 mapping has shown potential for local functional imaging without contrast material. Recently, it was discovered that observed lung T1 depends on the measurement echo time (TE). PURPOSE: To examine TE-dependence of observed T1 in patients with CF and its correlation with clinical metrics. STUDY TYPE: Prospective. POPULATION: In all, 75 pediatric patients with CF (8.6 ± 6.1 years, range 0.1-23 years), with 32 reexamined after 1 year. FIELD STRENGTH/SEQUENCE: Patients were examined at 1.5T using an established MRI protocol and a multiecho inversion recovery 2D ultrashort echo time (UTE) sequence for T1 (TE) mapping at five TEs including TE1 = 70 µs. ASSESSMENT: Morphological and perfusion MRI were assessed by a radiologist (M.W.) with 11 years of experience using an established CF-MRI scoring system. T1 (TE) was quantified automatically. Clinical data including spirometry (FEV1pred%) and lung clearance index (LCI) were collected. STATISTICAL TESTS: T1 (TE) was correlated with the CF-MRI score, clinical data, and LCI. RESULTS: T1 (TE) showed a different curvature in CF than in healthy adults: T1 at TE1 was shorter in CF (1157 ms ± 73 ms vs. 1047 ms ± 70 ms, P < 0.001), but longer at TE3 (1214 ms ± 72 ms vs. 1314 ms ± 68 ms, P < 0.001) and later TEs. The correlations of T1 (TE) with patient age (ρTE1-TE5 = -0.55, -0.44, -0.24, -0.30, -0.22), and LCI (ρTE1-TE5 = -0.43, -0.42, -0.33, 0.27, -0.22) were moderate at ultra-short to short TE (P < 0.001) but decreased for longer TE. Moderate but similar correlations at all TE were found with MRI perfusion score (ρTE1-TE5 = -0.43, -0.51, -0.47, -0.46, -0.44) and FEV1pred% (ρTE1-TE5 = +0.44, +0.44, +0.43, +0.40, +0.39) (P < 0.05). DATA CONCLUSION: TE should be considered when measuring lung T1 , since observed differences between CF and healthy subjects strongly depend on TE. The different variation of correlation coefficients with TE for structural vs. functional metrics implies that TE-dependence holds additional information which may help to discern effects of tissue structural abnormalities and abnormal perfusion. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1645-1654.

Chronic Thromboembolic Pulmonary Hypertension Perioperative Monitoring Using Phase-Resolved Functional Lung (PREFUL)-MRI.

BACKGROUND: The translation of phase-resolved functional lung (PREFUL)-MRI to routine practice in monitoring chronic thromboembolic pulmonary hypertension (CTEPH) still requires clinical corresponding imaging biomarkers of pulmonary vascular disease. PURPOSE: To evaluate successful pulmonary endarterectomy (PEA) via PREFUL-MRI with pulmonary pulse wave transit time (pPTT). STUDY TYPE: Retrospective. POPULATION: Thirty CTEPH patients and 12 healthy controls were included. FIELD STRENGTH/SEQUENCE: For PREFUL-MRI a 2D spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories (TWIST) sequence were performed on 1.5T. ASSESSMENT: Eight coronal slices of PREFUL-MRI were obtained on consecutive 13 days before and 14 days after PEA. PREFUL quantitative lung perfusion (PREFULQ ) phases over the whole cardiac cycle were calculated to quantify pPTT, the time the pulmonary pulse wave travels from the central pulmonary arteries to the pulmonary capillaries. Also, perfusion defect percentage based on pPTT (QDPpPTT ), PREFULQ (QDPPREFUL ), and V/Q match were calculated. For DCE-MRI, pulmonary blood flow (PBF) and QDPPBF were computed as reference. For clinical correlation, mean pulmonary arterial pressure (mPAP) and 6-minute walking distance were evaluated preoperatively and after PEA. STATISTICAL TESTS: The Shapiro-Wilk test, paired two-sided Wilcoxon rank sum test, Dice coefficient, and Spearman's correlation coefficient (ρ) were applied. RESULTS: Median pPTT was significantly lower post PEA (139 msec) compared to pre PEA (193 msec), P = 0.0002. Median pPTT correlated significantly with the mPAP post PEA (r = 0.52, P < 0.008). Median pPTT was distributed more homogeneously after PEA: IQR pPTT decreased from 336 to 281 msec (P < 0.004). Median PREFULQ (P < 0.0002), QDPpPTT (P < 0.0478), QDPPREFUL (P < 0.0001) and V/Q match (P < 0.0001) improved significantly after PEA. Percentage change of PREFULQ correlated significantly with percentage change of 6-minute walking distance (ρ = 0.61; P = 0.0031) 5 months post PEA. DATA CONCLUSION: Perioperative perfusion changes in CTEPH can be detected and quantified by PREFUL-MRI. Normalization of pPTT reflects surgical success and improvement of PREFULQ predicts 6-minute walking distance changes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:610-619.

UTE-SENCEFUL: first results for 3D high-resolution lung ventilation imaging.

PURPOSE: This study aimed to develop a 3D MRI technique to assess lung ventilation in free-breathing and without the administration of contrast agent. METHODS: A 3D-UTE sequence with a koosh ball trajectory was developed for a 3 Tesla scanner. An oversampled k-space was acquired, and the direct current signal from the k-space center was used as a navigator to sort the acquired data into 8 individual breathing phases. Gradient delays were corrected, and iterative SENSE was used to reconstruct the individual timeframes. Subsequently, the signal changes caused by motion were eliminated using a 3D image registration technique, and ventilation-weighted maps were created by analyzing the signal changes in the lung tissue. Six healthy volunteers and 1 patient with lung cancer were scanned with the new 3D-UTE and the standard 2D technique. Image quality and quantitative ventilation values were compared between both methods. RESULTS: UTE-based self-gated noncontrast-enhanced functional lung (SENCEFUL) MRI provided a time-resolved reconstruction of the breathing motion, with a 49% increase of the SNR. Ventilation quantification for healthy subjects was in statistical agreement with 2D-SENCEFUL and the literature, with a mean value of 0.11 ± 0.08 mL/mL for the whole lung. UTE-SENCEFUL was able to visualize and quantify ventilation deficits in a patient with lung tumor that were not properly depicted by 2D-SENCEFUL. CONCLUSION: UTE-SENCEFUL represents a robust MRI method to assess both morphological and functional information of the lungs in 3D. When compared to the 2D approach, 3D-UTE offered ventilation maps with higher resolution, improved SNR, and reduced ventilation artifacts.

MRI-derived regional flow-volume loop parameters detect early-stage chronic lung allograft dysfunction.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a major cause for the low long-term survival rates after lung transplantation (LTx). Early detection of CLAD may enable providing medical treatment before a nonreversible graft dysfunction has occurred. MRI is advantageous to pulmonary function testing (PFT) in the ability to assess regional function changes, and thus have the potential in detecting very early stages of CLAD before changes in global forced expiratory volume during the first second (FEV1%) occur. PURPOSE: To examine whether early stages of CLAD (diagnosed based on PFT values) could also be detected using MRI-derived parameters of regional flow-volume dynamics. STUDY TYPE: Retrospective. POPULATION: 62 lung transplantation recipients were included in the study, 29 of which had been diagnosed with CLAD at various stages. FIELD STRENGTH/SEQUENCE: MRI datasets were acquired with a 1.5T Siemens scanner using a spoiled gradient echo sequence. ASSESSMENT: MRI datasets were retrospectively preprocessed and analyzed by a blinded radiologist according to the phase resolved functional lung MRI (PREFUL-MRI) approach, resulting in fractional ventilation (FV) maps and regional flow-volume loops (rFVL). FV- and rFVL-based parameters of regional lung ventilation were estimated. STATISTICAL TESTS: Differences between groups were compared by Mann-Whitney U-test with a Bonferroni correction for multiple comparisons (n = 2). RESULTS: rFVL-CC-based parameters discriminated significantly between the presence or absence of CLAD (P < 0.003). DATA CONCLUSION: Using the contrast media-free PREFUL-MRI technique, parameters of ventilation dynamics and its regional heterogeneity were shown to be sensitive for the detection of early CLAD stages. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3 J. Magn. Reson. Imaging 2019;50:1873-1882.

Integrated EIT system for functional lung ventilation imaging.

BACKGROUND: Electrical impedance tomography (EIT) has been used for functional lung imaging of regional air distributions during mechanical ventilation in intensive care units (ICU). From numerous clinical and animal studies focusing on specific lung functions, a consensus about how to use the EIT technique has been formed lately. We present an integrated EIT system implementing the functions proposed in the consensus. The integrated EIT system could improve the usefulness when monitoring of mechanical ventilation for lung protection so that it could facilitate the clinical acceptance of this new technique. METHODS: Using a custom-designed 16-channel EIT system with 50 frames/s temporal resolution, the integrated EIT system software was developed to implement five functional images and six EIT measures that can be observed in real-time screen view and analysis screen view mode, respectively. We evaluated the performance of the integrated EIT system with ten mechanically ventilated porcine subjects in normal and disease models. RESULTS: Quantitative and simultaneous imaging of tidal volume (TV), end-expiratory lung volume change ([Formula: see text]EELV), compliance, ventilation delay, and overdistension/collapse images were performed. Clinically useful parameters were successfully extracted including anterior/posterior ventilation ratio (A/P ratio), center of ventilation ([Formula: see text], [Formula: see text]), global inhomogeneity (GI), coefficient of variation (CV), ventilation delay and percentile of overdistension/collapse. The integrated EIT system was demonstrated to suggest an optimal positive end-expiratory pressure (PEEP) for lung protective ventilation in normal and in the disease model of an acute injury. Optimal PEEP for normal and disease model was 2.3 and [Formula: see text], respectively. CONCLUSIONS: The proposed integrated approach for functional lung ventilation imaging could facilitate clinical acceptance of the bedside EIT imaging method in ICU. Future clinical studies of applying the proposed methods to human subjects are needed to show the clinical significance of the method for lung protective mechanical ventilation and mechanical ventilator weaning in ICU.

Imaging lung tissue oscillations using high-speed X-ray velocimetry.

This work utilized synchrotron imaging to achieve a regional assessment of the lung's response to imparted oscillations. The forced oscillation technique is increasingly being used in clinical and research settings for the measurement of lung function. During the forced oscillation technique, pressure oscillations are imparted to the lungs via the subjects' airway opening and the response is measured. This provides information about the mechanical properties of the airways and lung tissue. The quality of measurements is dependent upon the input signal penetrating uniformly throughout the lung. However, the penetration of these signals is not well understood. The development and use of a novel image-processing technique in conjunction with synchrotron-based imaging was able to regionally assess the lungs' response to input pressure oscillation signals in anaesthetized mice. The imaging-based technique was able to quantify both the power and distribution of lung tissue oscillations during forced oscillations of the lungs. It was observed that under forced oscillations the apices had limited lung tissue expansion relative to the base. This technique could be used to optimize input signals used for the forced oscillation technique or potentially as a diagnostic tool itself.