Lung Perfusion Research Articles

Quantitative texture analysis using machine learning for predicting interpretable pulmonary perfusion from non-contrast computed tomography in pulmonary embolism patients

BackgroundPulmonary embolism (PE) is life-threatening and requires timely and accurate diagnosis, yet current imaging methods, like computed tomography pulmonary angiography, present limitations, particularly for patients with contraindications to iodinated contrast agents. We aimed to develop a quantitative texture analysis pipeline using machine learning (ML) based on non-contrast thoracic computed tomography (CT) scans to discover intensity and textural features correlated with regional lung perfusion (Q) physiology and pathology and synthesize voxel-wise Q surrogates to assist in PE diagnosis.MethodsWe retrospectively collected 99mTc-labeled macroaggregated albumin Q-SPECT/CT scans from patients suspected of PE, including an internal dataset of 76 patients (64 for training, 12 for testing) and an external testing dataset of 49 patients. Quantitative CT features were extracted from segmented lung subregions and underwent a two-stage feature selection pipeline. The prior-knowledge-driven preselection stage screened for robust and non-redundant perfusion-correlated features, while the data-driven selection stage further filtered features by fitting ML models for classification. The final classification model, trained with the highest-performing PE-associated feature combination, was evaluated in the testing cohorts based on the Area Under the Curve (AUC) for subregion-level predictability. The voxel-wise Q surrogate was then synthesized using the final selected feature maps (FMs) and model score maps (MSMs) to investigate spatial distributions. The Spearman correlation coefficient (SCC) and Dice similarity coefficient (DSC) were used to assess the spatial consistency between FMs or MSMs and Q-SPECT scans.ResultsThe optimal model performance achieved an AUC of 0.863 during internal testing and 0.828 on the external testing cohort. The model identified a combination containing 14 intensity and textural features that were non-redundant, robust, and capable of distinguishing between high- and low-functional lung regions. Spatial consistency assessment in the internal testing cohort showed moderate-to-high agreement between MSMs and reference Q-SPECT scans, with median SCC of 0.66, median DSCs of 0.86 and 0.64 for high- and low-functional regions, respectively.ConclusionsThis study validated the feasibility of using quantitative texture analysis and a data-driven ML pipeline to generate voxel-wise lung perfusion surrogates, providing a radiation-free, widely accessible alternative to functional lung imaging in managing pulmonary vascular diseases.Clinical trial numberNot applicable.

Diagnosis of chronic thromboembolic pulmonary disease from an intensive pulmonary embolism treatment center

Abstract Background The diagnosis of Chronic Thromboembolic Pulmonary Disease (CTEPD) following an episode of acute pulmonary embolism (PE) has exhibited inconsistencies across different healthcare institutions, and the issue of underdiagnosis remains unresolved. Purpose The aim of this study is to ascertain the incidence of CTEPD following an episode of acute PE through a follow-up conducted at a specialized PE outpatient clinic located within a PE expert center. Methods and Results In this retrospective study, a cohort of 106 consecutive patients (mean age: 63.7±17.5 years, female: 51.9%) diagnosed with acute PE between March 2015 and August 2020 at our hospital were included. Patients who were capable of visiting the hospital received follow-up care at an outpatient clinic specializing in PE. The diagnosis of CTEPD was established in cases where patients, regardless of the presence of pulmonary hypertension, exhibited chronic-phase dyspnea and demonstrated perfusion defects on lung perfusion scintigraphy. Furthermore, individuals with a mean pulmonary arterial pressure ≥25 mmHg and a pulmonary capillary wedge pressure ≤15 mmHg, as determined by right heart catheterization, were diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). During the follow-up period (median duration: 27.5 months), 23 patients were diagnosed with CTEPD, and 10 patients were diagnosed with CTEPH. The cumulative incidence rates of CTEPD and CTEPH were as follows: 20.8% and 10.8% at 1 year, 26.9% and 12.7% at 2 years, respectively; and 28.9% at 3 years for CTEPD. Signs of RV dysfunction on CT or Echocardiography may have contributed to the detection of CTEPH and were discussed with respect to parameters indicating RVdisfunction. Conclusions In present study, the cumulative incidence of CTEPD and CTEPH is notably elevated. This results suggest that active surveillance after acute PE follow-up practices may have contributed to an enhanced rate of diagnosis or that chronic PE or CTEPH may have been included at the time of PE diagnosis.Cumulative Incidence of CTEPDCumulative Incidence of CTEPH

Feasibility of quantitative evaluation of hemodynamics using SPECT/CT in patients with chronic thromboembolic pulmonary hypertension

Abstract Background A ventilation/perfusion (V/Q) lung scan is recommended in the diagnostic work-up of patients with newly diagnosed pulmonary hypertension to rule out chronic thromboembolic pulmonary hypertension (CTEPH). V/Q single-photon emission computed tomography (SPECT) is considered the method of choice for diagnosis in CTEPH because it allows more precise evaluation than planar imaging. However, the evaluation of lung perfusion using V/Q SPECT imaging remains mainly a qualitative evaluation, and no quantitative method has been established. We hypothesized that the standardized uptake value (SUV) technique in Positron Emission Tomography (PET)-CT, a nuclear imaging technique well suited for quantitative of tumor biology, could be applied to quantitative assessment of lung perfusion. Purpose The purpose of this study was to evaluate the correlation between pulmonary perfusion distribution and hemodynamic data in Tc-labeled large-assembly albumin (99mTc-MAA) SPECT images in order to determine the feasibility of SPECT/CT for quantitative assessment of lung perfusion. Methods Twenty-five patients with CTEPH who underwent BPA and received SPECT-CT were included. Since the injected 99mTc-MAA selectively accumulates only in the lungs, SUV normalization was conducted using each patient’s lung volume, calculated by SPECT/CT and defined as SUV lung volume (LV) . The percentage of lung volume below each SUVLV value in total lung volume on SPECT/CT was examined before BPA, after two procedures of BPA, and six months after a series of BPA, and the correlations with hemodynamic parameters on right heart catheterization at each time point were evaluated. Results The Percent lung volume below SUVLV of 0.7 in total lung volume before BPA, after two procedures of BPA, and six months after a series of BPA had the strongest correlation with mean pulmonary artery pressure (mPAP) (rs; 0.727, p<0.001, Figure 1). The percent lung volume below SUVLV of 0.7 decreased with the BPA procedure in each patient with CTEPH (Figure 2). Furthermore, receiver operating characteristic analysis revealed that a threshold for the percent lung volume below SUVLV of 0.7 of 50.3% or greater could identify mPAP greater than 21 mmHg for right heart catheterization (area under the curve = 0.86, 95% CI 0.78-0.94, p<0.001). Conclusion Percent lung volume below SUVLV of 0.7 in total lung volume using SPECT/CT might reflect the severity of hemodynamics in patients with CTEPH. This method would be feasible for quantitative assessment of lung perfusion, even inter-patient and intra-patient.Figure 1Figure 2

Establishment of a Novel Ex Vivo Lung Perfusion System for Rat Lungs After Circulatory Death

Establishment of a Novel Ex Vivo Lung Perfusion System for Rat Lungs After Circulatory Death

Validation of a radiosynthesis method and a novel quality control system for [68 Ga]Ga-MAA: is TLC enough to assess radiopharmaceutical quality?

BackgroundTechnetium-99 m-labelled macroaggregated human serum albumin ([99mTc]Tc-MAA) is commonly used for lung perfusion scintigraphy. The European Pharmacopoeia (Eu.Ph.) specifies thin-layer chromatography (TLC) as the only method to assess its radiochemical purity (RCP). Similarly, TLC is the sole method reported in the literature to evaluate the RCP of Gallium-68-labelled MAA [68 Ga]Ga-MAA, recently introduced for lung perfusion PET/CT imaging. Since [68 Ga]Ga-MAA is prepared from commercial kits originally designed for the preparation of [99mTc]Tc-MAA, it is essential to optimize and validate the preparation methods for [68 Ga]Ga-MAA.ResultsWe tested a novel, simplified method for the preparation of [68 Ga]Ga-MAA that does not require organic solvents, prewash or final purification steps to remove radioactive impurities. We assessed the final product using radio-TLC, radio-UV-HPLC, and radio SDS-PAGE. Overall, our quality control (QC) method successfully detected [68 Ga]Ga-MAA along with all potential impurities, including free Ga-68, [68 Ga]Ga-HSA, unlabeled HSA, which may occur during labelling process and HEPES residual, a non-toxic but non-human-approved contaminant, used as buffer solution. We then applied our QC system to [68 Ga]Ga-MAA prepared under different conditions (25°–40°–75°–95 °C), thus defining the optimal temperature for labelling. Scanning Electron Microscopy (SEM) analysis of the products obtained through our novel method confirmed that most [68 Ga]Ga-MAA particles preserved the morphological structure and size distribution of unlabeled MAA, with a particle diameter range of 25–50 μm, assuring diagnostic efficacy.ConclusionsWe optimized a novel method to prepare [68 Ga]Ga-MAA through a QC system capable of monitoring all impurities of the final products.

Improving prognostic accuracy in lung transplantation using unique features of isolated human lung radiographs

Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases. Latent features were transformed into principal components (PC) and correlated with known radiographic findings. PCs were combined with physiological data to classify clinical outcomes: (1) recipient time to extubation of <72 h, (2) ≥ 72 h, and (3) lungs unsuitable for transplantation. The top PC was significantly correlated with infiltration (Spearman R: 0·72, p < 0·0001), and adding radiographic PCs significantly improved the discrimination for clinical outcomes (Accuracy: 73 vs 78%, p = 0·014). CNN-derived radiographic lung features therefore add substantial value to the current assessments. This approach can be adopted by EVLP centers worldwide to harness radiographic information without requiring real-time radiological expertise.

The combination of postmortem sevoflurane ventilation and in situ topical cooling provides improved 6 hours lung preservation in an uncontrolled DCD porcine model

BackgroundRecent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3h post-mortem. This study aims to investigate the additive effects of in situ lowering of intrathoracic temperature and sevoflurane preconditioning on lung grafts in a porcine uDCD model. MethodsAfter uDCD induction, donor pigs were allocated to one of the following groups: Control – static lung inflation only (SLI); TC – SLI + continuous intrapleural topical cooling (TC); or TC+Sevo – SLI + TC + sevoflurane. Lungs were retrieved 6h post-asystole and evaluated via ex vivo lung perfusion (EVLP) for 6h. A left single lung transplant was performed using lungs from the best performing group, followed by 4h of graft evaluation. ResultsAnimals that received topical cooling achieved intrathoracic temperature < 15°C within 1 hour after chest filling of coolant. Only lungs from donors that received TC and TC+Sevo completed the planned post-preservation 6h EVLP assessment. Despite similar early performance of the two groups on EVLP, the TC+Sevo group was superior - associated with overall lower airway pressures, higher pulmonary compliances, less edema development, and less release of inflammatory cytokines. Transplantation was performed using lungs from the TC+Sevo group, and excellent graft function was observed post-reperfusion. ConclusionPreservation of uDCD lungs with a combination of static lung inflation, topical cooling and sevoflurane treatment maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions may significantly expand the clinical utilization of uDCD donor lungs.

Outcomes of Donation After Circulatory Death (DCD) and Ex-Vivo Lung Perfusion (EVLP) Lung Transplantation

BackgroundDonation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) have been adopted to expand the donor pool in lung transplantation, but outcomes data have been conflicting. This study explores mid-term outcomes of DCD lung transplantation in the modern era, with a focus on EVLP and risk factors for graft failure. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from 1/1/2015 to 3/1/2023. Loss to follow-up, multiorgan and prior lung transplants were excluded. DCD vs DBD (donation after brain death) lung transplants were compared, with subgroup analysis +/- EVLP. Outcomes were survival and postoperative complications. Overall survival was analyzed separately for an early era (2015-2018) and modern era (2019-2023). ResultsThe study included 1103 DCD (221 with EVLP, and 882 without) and 17973 donation after brain death (DBD) lung transplants (524 with EVLP, and 17449 without). Median follow-up was 3 years. DCD donors were less likely to be CDC high risk (19.3% vs 24.1%, p<0.001), have purulence on bronchoscopy (13.3% vs 18.3%, p<0.001) or infiltrates on chest x-ray (66.7% vs 67.8%, p=0.013). EVLP was more likely to be used for DCD transplants (20.0% vs 2.9%, p<0.001).After transplant, DCD recipients were more likely to be reintubated (24.3% vs 18.5%, p<0.001) and require ECMO within 72 hours (14.9% vs 7.8%, p<0.001), and DCD donation was an independent risk factor for these complications on multivariable logistic regression. Overall survival did not differ significantly between DCD and DBD transplants on adjusted survival analysis in the early or modern era (p=0.774 and p=0.468 respectively). On multivariable Cox regression, DCD and EVLP were not independent risk factors for mortality.On subgroup analysis, the DCD+EVLP cohort had significantly worse survival in the modern era, which remained significant after adjusting for donor and recipient factors (p=0.005). EVLP was an independent risk factor for graft failure in the DCD cohort (HR 1.33, 95% CI 1.00-1.77, p=0.047), but did not significantly affect DBD graft survival (p=0.870). Risk factors for graft failure and mortality in the DCD+EVLP cohort included pulmonary hypertension (HR 77.5, 95% CI 6.15-979, p<0.001), transfusion prior to transplant (HR 2.60, 95% CI 1.07-6.31, p=0.035), elevated creatinine (HR 2.82, 95% CI 1.34-5.90, p=0.006), and higher allocation score (HR 1.02, 95% CI 1.00-1.04, p=0.017) ConclusionStudy findings suggest increased risks of mortality and perioperative complications following transplantation with DCD lungs that have undergone EVLP. DCD lung transplantation without EVLP confers equivalent survival but with some increase in perioperative complications. Further investigation and careful recipient selection is warranted to optimize the use of these extended criteria donors in the modern era.

IPhone or Blackberry? The unsure future of Ex-Vivo Lung Perfusion: A Commentary on Ex-Vivo Lung Perfusion National Trends and Post-Transplant Outcomes

iPhone or Blackberry? The unsure future of Ex-Vivo Lung Perfusion: A Commentary on Ex-Vivo Lung Perfusion National Trends and Post-Transplant Outcomes

Predicting Primary Graft Dysfunction in Lung Transplantation: Machine Learning-Guided Biomarker Discovery.

There is an urgent need to better understand the pathophysiology of primary graft dysfunction (PGD) so that point-of-care methods can be developed to predict those at risk. Here we utilize a multiplex multivariable approach to define cytokine, chemokines, and growth factors in patient-matched biospecimens from multiple biological sites to identify factors predictive of PGD. Biospecimens were collected from patients undergoing bilateral LTx from three distinct sites: donor lung perfusate, post-transplant bronchoalveolar lavage (BAL) fluid (2h), and plasma (2h and 24h). A 71-multiplex panel was performed on each biospecimen. Cross-validated logistic regression (LR) and random forest (RF) machine learning models were used to determine whether analytes in each site or from combination of sites, with or without clinical data, could discriminate between PGD grade 0 ( n = 9) and 3 ( n = 8). Using optimal AUROC, BAL fluid at 2h was the most predictive of PGD (LR, 0.825; RF, 0.919), followed by multi-timepoint plasma (LR, 0.841; RF, 0.653), then perfusate (LR, 0.565; RF, 0.448). Combined clinical, BAL, and plasma data yielded strongest performance (LR, 1.000; RF, 1.000). Using a LASSO of the predictors obtained using LR, we selected IL-1RA, BCA-1, and Fractalkine, as most predictive of severe PGD. BAL samples collected 2h post-transplant were the strongest predictors of severe PGD. Our machine learning approach not only identified novel cytokines not previously associated with PGD, but identified analytes that could be used as a point-of-care cytokine panel aimed at identifying those at risk for developing severe PGD.

Pushing the Survival Bar Higher: Two Decades of Innovation in Lung Transplantation.

Survival after lung transplantation has significantly improved during the last two decades. The refinement of the already existing extracorporeal life support (ECLS) systems, such as extracorporeal membrane oxygenation (ECMO), and the introduction of new techniques for donor lung optimization, such as ex vivo lung perfusion (EVLP), have allowed the extension of transplant indication to patients with end-stage lung failure after acute respiratory distress syndrome (ARDS) and the expansion of the donor organ pool, due to the better evaluation and optimization of extended-criteria donor (ECD) lungs and of donors after circulatory death (DCD). The close monitoring of anti-HLA donor-specific antibodies (DSAs) has allowed the early recognition of pulmonary antibody-mediated rejection (AMR), which requires a completely different treatment and has a worse prognosis than acute cellular rejection (ACR). As such, the standardization of patient selection and post-transplant management has significantly contributed to this positive trend, especially at high-volume centers. This review focuses on lung transplantation after ARDS, on the role of EVLP in lung donor expansion, on ECMO as a principal cardiopulmonary support system in lung transplantation, and on the diagnosis and therapy of pulmonary AMR.

Pulmonary emphysema: the assessment of lung perfusion with Dual-Energy CT and pulmonary scintigraphy.

To assess the correlation of quantitative data of pulmonary Perfused Blood Volume (PBV) on Dual-Energy CT (DECT) datasets in patients with moderate - severe Pulmonary Emphysema (PE) with Lung Perfusion Scintigraphy (LPS) as the reference standard. The secondary endpoints are the correlation between the CT densitometric analysis and the visual assessment of parenchymal destruction with PBV. Patients with moderate - severe PE candidate to Lung Volumetric Reduction (LVR), with available a pre-procedural LS and a contrast-enhanced DECT were retrospectively included. DECT studies were performed with a 3rd generation Dual-Source CT and the PBV was obtained with a 3-material decomposition algorithm. The CT densitometric analysis was performed with a dedicated commercial software (Pulmo3D). The Goddard Score was used for visual assessment. The perfusion LS were performed after the administration of albumin macroaggregates labeled with 99mTechnetium. The image revision was performed by two radiologists or nuclear medicine physicians blinded, respectively, to LS and DECT data. The statistical analysis was performed with nonparametric tests. Thirty-one patients (18 males, median age 69 y.o., interquartile range 62-71 y.o.) with moderate - severe PE (Median Goddard Score 14/20 and 31% of emphysematous parenchyma at quantitative CT) candidate to LVR were retrospectively included. The median enhancement on PBV was 17 HU. Significant correlation coefficients were demonstrated between lung PBV and LS, poor in apical regions (Rho = 0.1-0.2) and fair (Rho = 0.3-0.5) in middle and lower regions. No significant correlations were recorded between the CT densitometric analysis, the visual score, and the PBV. Lung perfusion with PBV on DECT is feasible in patients with moderate - severe PE candidate to LVR, and has a poor to fair agreement with LPS.

Comparing right- versus left-first implantation in off-pump sequential double-lung transplantation: an observational cohort study.

Historically, the perfusion-guided sequence suggests to first transplant the side with lowest lung perfusion. This sequence is thought to limit right ventricular afterload and prevent acute heart failure after first pneumonectomy. As a paradigm shift, we adopted the right-first implantation sequence, irrespective of lung perfusion. The right donor lung generally accommodates a larger proportion of the cardiac output. We hypothesized that the right-first sequence reduces the likelihood of oedema formation in the firstly transplanted graft during second-lung implantation. Our objective was to compare the perfusion-guided and right-first sequence for intraoperative extracorporeal membrane oxygenation (ECMO) need and primary graft dysfunction (PGD). A retrospective single-centre cohort study (2008-2021) including double-lung transplant cases (N = 696) started without ECMO was performed. Primary end-points were intraoperative ECMO cannulation and PGD grade 3 (PGD3) at 72 h. Secondary end-points were patient and chronic lung allograft dysfunction-free survival. In cases with native left lung perfusion ≤50% propensity score adjusted comparison of the perfusion-guided and right-first sequence was performed. When left lung perfusion was ≤50%, right-first implantation was done in 219 and left-first in 189 cases. Intraoperative escalation to ECMO support was observed in 10.96% of right-first versus 19.05% of left-first cases (odds ratio 0.448; 95% confidence interval 0.229-0.0.878; P = 0.0193). PGD3 at 72 h was observed in 8.02% of right-first versus 15.64% of left-first cases (0.566; 0.263-1.217; P = 0.1452). Right-first implantation did not affect patient or chronic lung allograft dysfunction-free survival. The right-first implantation sequence in off-pump double-lung transplantation reduces need for intraoperative ECMO cannulation with a trend towards less PGD grade 3.

Longitudinal Magnetic Resonance Imaging of Changes in Lung Morphology and Perfusion in Children with Cystic Fibrosis From Infancy through Adolescence.

The progression of lung changes in cystic fibrosis (CF) from infancy through adolescence remains poorly understood due to limited longitudinal imaging data. To assess changes in lung morphology and perfusion in children with CF through the pediatric age range by longitudinal chest magnetic resonance imaging (MRI). 1112 annual chest MRI were performed in 226 patients with CF aged 0-18yr. MRI was assessed using a validated MRI scoring system. The MRI global score continuously increased from 5.5±4.6 at infancy (0yr) to 17.9±8.4 at adolescence (range 12-18yr), and the MRI morphology score from 5.0±3.9 to 12.4±6.0 (P<0.001). Bronchiectasis/wall thickening prevalence increased from 89.1% at infancy to approx. 100% from preschool age (1-5yr), and the subscore increased from 3.1±1.9 at infancy to 6.6±2.1 at adolescence (P<0.001). Mucus plugging prevalence increased from 55.4% at infancy to 83.5% at adolescence, and the subscore increased from 1.2±1.6 to 3.7±2.5 in the same period (P<0.001). Perfusion abnormalities were found in 44.4% at infancy, and increased to approx. 90% from preschool age (P<0.001). The MRI perfusion score increased from 1.1±1.6 at infancy to 5.6±3.0 at adolescence (P<0.001). Chronic Pseudomonas aeruginosa infection was associated with higher MRI scores from school age (6-11yr, P<0.05-0.001). This is the first study assessing longitudinal changes in lung morphology and perfusion in CF throughout the pediatric age range, providing percentiles as age-specific reference for lung disease severity. Our data may facilitate the use of MRI as an endpoint in clinical trials in children with CF.

Low-Volume Ex Situ Lung Perfusion System for Single Lung Application in a Small Animal Model Enables Optimal Compliance With "Reduction" in 3R Principles of Animal Research.

Ex situ lung perfusion (ESLP) is used for organ reconditioning, repair, and re-evaluation prior to transplantation. Since valid preclinical animal models are required for translationally relevant studies, we developed a 17mL low-volume ESLP for double- and single-lung application that enables cost-effective optimal compliance "reduction" of the 3R principles of animal research. In single-lung mode, ten Fischer344 and Lewis rat lungs were subjected to ESLP and static cold storage using STEEN or PerfadexPlus. Key perfusion parameters, thermal lung imaging, blood gas analysis (BGA), colloid oncotic pressure (COP), lung weight gain, histological work-up, and cytokine analysis were performed. Significant differences between perfusion solutions but not between the rat strains were detected. Most relevant perfusion parameters confirmed valid ESLP with homogeneous lung perfusion, evidenced by uniform lung surface temperature. BGA showed temperature-dependent metabolic activities with differences depending on perfusion solution composition. COP is not decisive for pulmonary oedema and associated weight gain, but possibly rather observed chemokine profile and dextran sensitivity of rats. Histological examination confirmed intact lung architecture without infarcts or hemorrhages due to optimal organ procurement and single-lung application protocol using our in-house-designed ESLP system.

The effects of percutaneous branch pulmonary artery interventions in biventricular congenital heart disease: study protocol for a randomized controlled Dutch multicenter interventional trial

BackgroundBranch pulmonary artery (PA) stenosis is one of the most common indications for percutaneous interventions in patients with transposition of the great arteries (TGA), tetralogy of Fallot (ToF), and truncus arteriosus (TA). However, the effects of percutaneous branch PA interventions on exercise capacity remains largely unknown. In addition, there is no consensus about the optimal timing of the intervention for asymptomatic patients according to international guidelines. This trial aims to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with TGA, ToF, and TA. In addition, it aims to assess the effects on RV function and to define early markers for RV adaptation and RV dysfunction to improve timing of these interventions.MethodsThis is a randomized multicenter interventional trial. TGA, ToF, and TA patients ≥ 8 years with a class IIa indication for percutaneous branch PA intervention according to international guidelines are eligible to participate. Patients will be randomized into the intervention group or the control group (conservative management for 6 months). All patients will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and cardiopulmonary exercise testing at baseline, 6 months, and 2–4 years follow-up. Quality of life (QoL) questionnaires will be obtained at baseline, 2 weeks post intervention or a similar range for the control group, and 6 months follow-up. The primary outcome is exercise capacity expressed as maximum oxygen uptake (peak VO2 as percentage of predicted). A total of 56 patients (intervention group n = 28, control group n = 28) is required to demonstrate a 14% increase in maximum oxygen uptake (peak VO2 as percentage of predicted) in the interventional group compared to the control group (power 80%, overall type 1 error controlled at 5%). Secondary outcomes include various parameters for RV systolic function, RV functionality, RV remodeling, procedural success, complications, lung perfusion, and QoL.DiscussionThis trial will investigate the effects of percutaneous branch PA interventions on exercise capacity in patients with TGA, ToF, and TA and will identify early markers for RV adaptation and RV dysfunction to improve timing of the interventions.Trial registrationClinicalTrials.gov NCT05809310. Registered on March 15, 2023.

Therapeutic Use of Carbon Monoxide in Ex-Vivo Lung Perfusion in Donor With Prolonged Cold Ischemia

IntroductionCarbon monoxide (CO) has been shown to exert protective effects in multiple organs following ischemic injury, including the lung. The purpose of this study was to examine the effects of CO administration during ex vivo lung perfusion (EVLP) on lung grafts exposed to prolonged cold ischemia. MethodsTen porcine lungs were subjected to 18 h of cold ischemia followed by 6 h of EVLP. Lungs were randomized to EVLP alone (control, n = 5) or delivery of 500 ppm of CO during the 1st hour of EVLP (treatment, n = 5). Following EVLP, the left lungs were transplanted and reperfused for 4 h. ResultsAt the end of EVLP, pulmonary vascular resistance (P = 0.007) and wet to dry lung weight ratios (P = 0.027) were significantly reduced in CO treated lungs. Posttransplant, lung graft PaO2/FiO2 (P = 0.032) and compliance (P = 0.024) were significantly higher and peak airway pressure (P = 0.032) and wet to dry ratios (P = 0.003) were significantly lower in CO treated lungs. Interleukin-6 was significantly reduced in plasma during reperfusion in the CO treated group (P = 0.040). ConclusionsIn this preclinical porcine model, CO application during EVLP resulted in better graft performance and outcomes after reperfusion.

Physiological Comparison of Airway Pressure Release Ventilation and Low Tidal Volume Ventilation in Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

BackgroundThe physiological effects of different ventilation strategies on patients with acute respiratory distress syndrome (ARDS) need to be better understood. Research QuestionIn patients with ARDS under controlled mandatory ventilation, does airway pressure release ventilation (APRV) improve lung ventilation-perfusion matching and ventilation homogeneity compared to low tidal volume ventilation (LTV)? Study Design and MethodsThis study was a single-center randomized controlled trial. Patients with moderate-to-severe ARDS were randomly ventilated on APRV or LTV. Electrical impedance tomography (EIT) was utilized to assess lung ventilation and perfusion. EIT-based data and clinical variables related to respiratory and hemodynamic conditions were collected shortly before randomization (0h), and at 12 and 24 hours after randomization. ResultsA total of 40 subjects were included and randomized to the APRV or LTV group (20 per group). During the 24-hour trial period, patients on APRV exhibited significantly increased dorsal ventilation (difference value (24h-0h), median [25-75 percentiles]: 10.82% [2.62–13.74] vs 0.12% [-2.81–4.76], P = .017), decreased dorsal shunt (-4.67% [-6.83–0.59] vs 1.73% [-0.95–5.53], P = .008) and increased dorsal ventilation-perfusion matching (4.13% [-0.26–10.47] vs -3.29% [-5.05–2.81], P = .026) than those on LTV; no difference in ventral dead space was observed between study groups (P = .903). Additionally, two indicators of ventilation distribution heterogeneity: global inhomogeneity index significantly decreased, and center of ventilation significantly increased in the APRV group compared to the LTV group. Patients on APRV had significantly higher PaO2/FiO2, higher respiratory system static compliance (Crs) and lower PaCO2 than those on LTV at 24h. The cardiac output was comparable in both groups. InterpretationAPRV, as compared to LTV, could recruit dorsal region, reduce dorsal shunt, increase dorsal ventilation-perfusion matching, and improve ventilation homogeneity of the lungs, leading to better gas exchange and Crs in patients with moderate-to-severe ARDS.

366.6: Males and females respond differently to 17beta-estradiol and methylprednisolone associated treatment during ex vivo lung perfusion of brain death rats.

366.6: Males and females respond differently to 17beta-estradiol and methylprednisolone associated treatment during ex vivo lung perfusion of brain death rats.

V-312.3: Insights from platelet and leukocyte sequestration in pig lung perfusion with human blood: role of selectins, porcine sialoadhesin, and CD11b/CD18 Integrin.

V-312.3: Insights from platelet and leukocyte sequestration in pig lung perfusion with human blood: role of selectins, porcine sialoadhesin, and CD11b/CD18 Integrin.