Lung Perfusion Research Articles

Incidence of fatal and non-fatal pulmonary thromboembolism after removal of tunnelled central venous haemodialysis catheters without ultrasound scan and anticoagulation.

Catheter related thrombosis is a common complication of tunnelled central venous catheter (TCVC) usage. There are concerns that TCVC removal could dislodge a thrombus to cause pulmonary thromboembolism (PE). The incidence of PE following TCVC removal is unclear and so the aim of this study was to investigate the incidence of PE and whether it is high enough to warrant screening with ultrasound with a view to systemic anticoagulation prior to TCVC removal. 1102 consecutive TCVC removals without ultrasound and systemic anticoagulation were included in this retrospective study. Data were extracted from electronic health records. Measures to identify PE events included: deaths, computed tomography pulmonary angiogram (CT-PA), isotope lung perfusion scans and D-dimers blood tests within 7 days of removal. Of the 1102 TCVC removals, the mean age of patients was 56.9 years and 57.3% were male. The primary renal diagnosis for 24.5% of patients was diabetic nephropathy. There were seven deaths following removal, none of which had PE as a contributing cause on review of their clinical history and death certificates. Five CT-PAs and one isotope lung perfusion scan were carried out in the 7 days after TCVC removal and none had a positive finding of PE. Three patient had D-dimers measured in blood within 7 days and none of these patients were subsequently diagnosed with PE. There was no evidence of fatal or non-fatal PE's occurring in the 7 days following TCVC removal. This would support the practice of removing TCVCs without the need for ultrasound screening and without a period of systemic anticoagulation.

Centralized Static Ex Vivo Lung Perfusion in the United States

BackgroundEx vivo lung perfusion (EVLP) may improve donor lung utilization but requires significant infrastructure and expertise. Centralized EVLP facilities may mitigate these requirements. MethodsFrom the United Network for Organ Sharing database, we identified 345 adults undergoing isolated, first-time lung transplantation using donor lungs perfused by static EVLP (March 1, 2018-December 31, 2022). Recipients of lungs perfused at centralized EVLP facilities (n = 165) were compared with recipients of lungs perfused at individual transplant centers (n = 180). Propensity score matching was used to create balanced groups for comparison. ResultsCentralized EVLP facilities were increasingly used from 2018 to 2022 (35.3% vs 55.8%, P = .04) and were more likely used when the annual center volume of EVLP lung transplants was low. Compared with allografts placed on EVLP at individual transplant centers, those placed on EVLP at centralized facilities had longer median ischemic time (11.3 vs 9.6 hours, P < .001) and were less likely to come from donation after circulatory death donors (25.4% vs 39.5%, P = .003) or be used for double-lung transplant (73.3% vs 83.9%, P = .02). In 102 well-matched recipient pairs, 2-year survival was equivalent between those receiving allografts perfused at centralized facilities (77.9%; 95% CI, 68.0%-85.1%) vs individual transplant centers (77.7%; 95% CI, 67.8%-84.9%; P = .90). Multivariable Cox regression analysis also showed equivalent 2-year survival (adjusted hazard ratio, 1.02; 95% CI, 0.57-1.84; P = .95). ConclusionsTransplanting lung allografts that underwent static EVLP at centralized facilities had similar outcomes compared with transplanting lungs perfused at individual transplant centers. The centralized model of clinical EVLP can potentially improve access to EVLP.

Impact of COVID-19 on Ventilation-Perfusion (V/Q) Scans: A Comparative Analysis of Pre-COVID-19 Era V/Q Scans and Post-COVID-19 Era Perfusion Scans.

Introduction The COVID-19 pandemic has profoundly impacted medical practices, including nuclear medicine. To minimize aerosol transmission risks, lung perfusion scintigraphy was preferred over traditional ventilation-perfusion (V/Q) scintigraphy during the pandemic. This study compares lung perfusion scans performed during COVID-19 with V/Q scans from the pre-COVID era. After reviewing this study, the reader will learn about V/Q scintigraphy and lung perfusion. Methods This retrospective observational study, conducted from December 2018 to July 2021, involved 868 patients - 511 in the pre-COVID era and 357 in the post-COVID era - at a single tertiary care center. The pretest probability of pulmonary embolism (PE) was determined using Wells' criteria, and data including demographics, clinical findings, and diagnostic test results (V/Q or lung perfusionscintigraphy) were collected. Results A 30% decline in lung scans was observed during the pandemic. In the pre-COVID era, 68.3% of scans had low, 27.8% had intermediate, and 3.9% had high probability for PE. During the pandemic, perfusion-only scans showed 57.3% low, 32.9% indeterminate, and 9.8% high probability for PE. Among COVID-19-positive patients, 48.9% had intermediate, and 11.1% had high probability scans. The rise in indeterminate and high-probability scans during the pandemic is attributed to COVID-19-related lung changes and hypercoagulability. Conclusion The perfusion component of lung scans is typically sufficient for evaluating acute PE. Omitting the ventilation part of the V/Q scan had minimal impact, with only a 5.1% increase in indeterminate/non-diagnostic scans using perfusion-only modified Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) criteria during the post-COVID-19 era, likely due to underlying lung parenchymal involvement in COVID-19 patients. Additionally, there was a 5.9% rise in high-probability scans, attributed to the hypercoagulability and vascular complications associated with COVID-19.

Amniotic fluid-derived mesenchymal stem cells reduce inflammation and improve lung function following transplantation in a porcine model

BackgroundLung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and post-operative outcomes. MethodsIn a transplantation model, donor pigs were stratified to either the treated or the non-treated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion before transplantation. Treatment consisted of three doses of 2x106 cells/kg: one during ex vivo lung perfusion and two after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD). ResultsRepeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO2/FiO2 ratios and reduced incidence of PGD. ConclusionsRepeated injection of lung-specific cell treatment during EVLP and post-transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of post-operative outcomes.

Orthostatic Ex-Vivo Lung Perfusion (EVLP): A Proof of Concept.

The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the "Achilles' heel" of the EVLP due to a more fluid accumulation than in the supine standard position.

Ex Vivo Lung Perfusion and Primary Graft Dysfunction Following Lung Transplantation: A Contemporary United Network for Organ Sharing Database Analysis.

Background: Primary graft dysfunction (PGD) has detrimental effects on recipients following lung transplantation. Here, we determined the contemporary trends of PGD in a national database, factors associated with the development of PGD grade 3 (PGD3) and ex vivo lung perfusion's (EVLP) effect on this harmful postoperative complication. Methods: The United Network for Organ Sharing database was queried from 2015 to 2023, and recipients were stratified into No-PGD, PGD1/2, or PGD3. The groups were analyzed with comparative statistics, and survival was determined with Kaplan-Meier methods. Multivariable Cox regression was used to determine factors associated with increased mortality. PGD3 recipients were then stratified based on EVLP use prior to transplantation, and a 3:1 propensity match was performed to determine outcomes following transplantation. Finally, logistic regression models based on select criteria were used to determine risk factors associated with the development of PGD3 and mortality within 1 year. Results: A total of 21.4% of patients were identified as having PGD3 following lung transplant. Those with PGD3 suffered significantly worse perioperative morbidity, mortality, and had worse long-term survival. PGD3 was also independently associated with increased mortality. Matched EVLP PGD3 recipients had significantly higher use of ECMO postoperatively; however, they did not suffer other significant morbidity or mortality as compared to PGD3 recipients without EVLP use. Importantly, EVLP use prior to transplantation was significantly associated with decreased likelihood of PGD3 development, while having no significant association with early mortality. Conclusions: EVLP is associated with decreased PGD3 development, and further optimization of this technology is necessary to expand the donor pool.

Knockdown of swine leukocyte antigen expression in porcine lung transplants enables graft survival without immunosuppression.

Immune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects. To address this problem, we investigated the effect of genetically engineered transplants with permanently down-regulated swine leukocyte antigen (SLA) expression to prevent rejection in a porcine allogeneic lung transplantation (LTx) model. Minipig donor lungs with unmodified SLA expression (control group, n = 7) or with modified SLA expression (treatment group, n = 7) were used to evaluate the effects of SLA knockdown on allograft survival and on the nature and strength of immune responses after terminating an initial 4-week period of immunosuppression after LTx. Genetic engineering to down-regulate SLA expression was achieved during ex vivo lung perfusion by lentiviral transduction of short hairpin RNAs targeting mRNAs encoding β2-microglobulin and class II transactivator. Whereas all grafts in the control group were rejected within 3 months, five of seven animals in the treatment group maintained graft survival without immunosuppression during the 2-year monitoring period. Compared with controls, SLA-silenced lung recipients had lower donor-specific antibodies and proinflammatory cytokine concentrations in the serum. Together, these data demonstrate a survival benefit of SLA-down-regulated lung transplants in the absence of immunosuppression.

Clinical Factors Affecting Discrepancy Between Predicted and Long-term Actual Lung Function Following Surgery.

Lung cancer surgery outcomes depend heavily on preoperative pulmonary reserve, with forced expiratory volume in 1 second (FEV1) being a critical preoperative evaluation factor. Our study investigates the discrepancies between predicted and long-term actual postoperative lung function, focusing on clinical factors affecting these outcomes. This retrospective observational study encompassed lung cancer patients who underwent preoperative lung perfusion SPECT/CT between 2015 and 2021. We evaluated preoperative and postoperative pulmonary function tests, considering factors such as surgery type, resected volume, and patient history including tuberculosis. Predicted postoperative lung function was calculated using SPECT/CT imaging. From 216 patients (men:women, 150:66; age, 67.9 ± 8.7 years), predicted postoperative FEV1% (ppoFEV1%) showed significant correlation with actual postoperative FEV1% (r = 0.667; P < 0.001). Paired t test revealed that ppoFEV1% was significantly lower compared with actual postoperative FEV1% (P < 0.001). The study identified video-assisted thoracic surgery (VATS) (odds ratio [OR], 3.90; 95% confidence interval [CI], 1.98-7.69; P < 0.001) and higher percentage of resected volume (OR per 1% increase, 1.05; 95% CI, 1.01-1.09; P = 0.014) as significant predictors of postsurgical lung function improvement. Conversely, for the decline in lung function postsurgery, significant predictors included lower percentage of resected lung volume (OR per 1% increase, 0.92; 95% CI, 0.86-0.98; P = 0.011), higher preoperative FEV1% (OR, 1.03; 95% CI, 1.01-1.07; P = 0.009), and the presence of tuberculosis (OR, 5.19; 95% CI, 1.48-18.15; P = 0.010). Additionally, in a subgroup of patients with borderline lung function, VATS was related with improvement. Our findings demonstrate that in more than half of the patients, actual postsurgical lung function exceeded predicted values, particularly following VATS and with higher volume of lung resection. It also identifies lower resected lung volume, higher preoperative FEV1%, and tuberculosis as factors associated with a postsurgical decline in lung function. The study underscores the need for precise preoperative lung function assessment and tailored postoperative management, with particular attention to patients with relevant clinical factors. Future research should focus on validation of clinical factors and exploring tailored approaches to lung cancer surgery and recovery.

Image quality of lung perfusion with photon-counting-detector CT: comparison with dual-source, dual-energy CT.

To evaluate the quality of lung perfusion imaging obtained with photon-counting-detector CT (PCD-CT) in comparison with dual-source, dual-energy CT (DECT). Seventy-one consecutive patients scanned with PCD-CT were compared to a paired population scanned with dual-energy on a 3rd-generation DS-CT scanner using (a) for DS-CT (Group 1): collimation: 64 × 0.6 × 2 mm; pitch: 0.55; (b) for PCD-CT (Group 2): collimation: 144 × 0.4 mm; pitch: 1.5; single-source acquisition. The injection protocol was similar in both groups with the reconstruction of perfusion images by subtraction of high- and low-energy virtual monoenergetic images. Compared to Group 1, Group 2 examinations showed: (a) a shorter duration of data acquisition (0.93 ± 0.1 s vs 3.98 ± 0.35 s; p < 0.0001); (b) a significantly lower dose-length-product (172.6 ± 55.14 vs 339.4 ± 75.64 mGy·cm; p < 0.0001); and (c) a higher level of objective noise (p < 0.0001) on mediastinal images. On perfusion images: (a) the mean level of attenuation did not differ (p = 0.05) with less subjective image noise in Group 2 (p = 0.049); (b) the distribution of scores of fissure visualization differed between the 2 groups (p < 0.0001) with a higher proportion of fissures sharply delineated in Group 2 (n = 60; 84.5% vs n = 26; 26.6%); (c) the rating of cardiac motion artifacts differed between the 2 groups (p < 0.0001) with a predominance of examinations rated with mild artifacts in Group 2 (n = 69; 97.2%) while the most Group 1 examinations showed moderate artifacts (n = 52; 73.2%). PCD-CT acquisitions provided similar morphologic image quality and superior perfusion imaging at lower radiation doses. The improvement in the overall quality of perfusion images at lower radiation doses opens the door for wider applications of lung perfusion imaging in clinical practice. The speed of data acquisition with PCD-CT accounts for mild motion artifacts. Sharply delineated fissures are depicted on PCD-CT perfusion images. High-quality perfusion imaging was obtained with a 52% dose reduction.

Development of a low priming volume hydrodynamic test bench for isolated ex vivo perfusion of small animal lungs

Development of a low priming volume hydrodynamic test bench for isolated ex vivo perfusion of small animal lungs

Normothermic Perfusion is Superior to Cold Perfusion in Porcine Ex Situ Lung Perfusion

BackgroundCold ex situ lung perfusion (ESLP) has demonstrated improved preservation in small animal ESLP compared to normothermic ESLP and cold static preservation. We hypothesized that cold negative pressure ventilation (NPV)-ESLP would improve graft function in a porcine transplantation model. MethodsFour perfusate temperatures were examined with 12 hours NPV-ESLP in a large animal transplantation model. Pig lungs were allotted to four groups: (1) Normothermia (38°C, n = 6); (2) profound hypothermia (10°C, n = 6); (3) moderate hypothermia (20°C, n = 3); (4) subnormothermia (32°C, n = 3). A fifth group subnormothermic low-flow (SNLF) perfusion was examined to assess the effect of reduced cardiac output with cold perfusion (32°C, 10% cardiac output, n = 6). ResultsOnly Normothermic and SNLF groups demonstrated acceptable oxygenation after 12 hours NPV-ESLP and were transplanted. All other groups failed prematurely. After 12 hours of ESLP, Normothermic lungs demonstrated significantly greater dynamic compliance compared to SNLF lungs (P = .03). Edema formation post-ESLP was significantly worse in the SNLF group (P = .01). There was no significant difference in pulmonary artery pressures after ESLP (P = .10); however, pulmonary vascular resistance was significantly greater in the SNLF (P = .04). Isolated left lung oxygenation 4-hours post-transplant and left lung edema formation was not significantly different between Normothermic and SNLF post-transplant (P = .09). Proinflammatory cytokines were significantly greater during SNLF-ESLP (tumor necrosis factor alpha, P < .05). ConclusionsProlonged normothermic (38°C) NPV-ESLP is superior to 10, 20, and 32°C perfusion. Normothermic ESLP of porcine lungs results in superior graft function and reduced inflammation versus SNLF-ESLP.

Restoring discarded porcine lungs by ex vivo removal of neutrophil extracellular traps

BackgroundBy causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx). MethodTo determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n=6) or EVLP only (non-treated) (n=6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs as well as cytokine levels. ResultsAfter EVLP and NET removal in porcine lungs, PaO2/FiO2 ratios increased significantly compared to those undergoing EVLP alone (p=0.0411). Treated lungs had lower cell-free DNA (p=0.0260) and lower levels of extracellular histones in EVLP perfusate than non-treated lungs (p=0.0260). According to histopathology, treated lungs showed less immune cell infiltration and less oedema compared with non-treated lungs which was reflected in decreased levels of pro-inflammatory cytokines in EVLP perfusate and BALF. ConclusionTo conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.

Determination of Cardiac Output in a Porcine Model for Ex Vivo Pulmonary Perfusion.

Due to their physiological similarities to humans, pigs are used as experimental models for ex vivo lung perfusion (EVLP). EVLP is a technique that perfuses lungs that are not suitable for transplantation via an extracorporeal circulation pump to improve their function and increase their viability. Existing EVLP protocols are differentiated by the type of perfusion solution and perfusion flow, which varies from 40%-100% of the estimated cardiac output (CO) according to the body surface area (BSA). Devices for measuring CO use simple physical principles and other mathematical models. Thermodilution in animal models continues to be the reference standard for estimating CO because of its simplicity and ease of reproduction. Therefore, the objective of this study was to reproduce the measurement of CO by thermodilution in pigs and compare its precision and accuracy with those obtained by the BSA, weight, and Fick's method, to establish perfusion flow during EVLP. In 23 pigs, a thermodilution catheter was placed in the right jugular vein, and the carotid artery on the same side was cannulated. Blood samples were obtained for gasometry, and CO was estimated by thermodilution, adjusted body surface area, Fick's principle, and per body weight. The CO obtained by the BSA was greater (p = 0.0001, ANOVA, Tukey) than that obtained by the other methods. We conclude that although the methods used in this study to estimate CO are reliable, there are significant differences between them; therefore, each method must be evaluated by the investigator to determine which meets the needs of the protocol.

Porcine lungs perfused with three different flows using the 8-h open-atrium cellular ex vivo lung perfusion technique.

The number of lung transplantations is limited due to the shortage of donor lungs fulfilling the standard criteria. The ex vivo lung perfusion (EVLP) technique provides the ability of re-evaluating and potentially improving and treating marginal donor lungs. Accordingly, the technique has emerged as an essential tool to increase the much-needed donor lung pool. One of the major EVLP protocols, the Lund protocol, characterized by high pulmonary artery flow (100% of cardiac output [CO]), an open atrium, and a cellular perfusate, has demonstrated encouraging short-EVLP duration results. However, the potential of the longer EVLP duration of the protocol is yet to be investigated, a duration which is considered necessary to rescue more marginal donor lungs in future. This study aimed to achieve stable 8-h EVLP using an open-atrium cellular model with three different pulmonary artery flows in addition to determining the most optimal flow in terms of best lung performance, including lung electrolytes and least lung edema formation, perfusate and tissue inflammation, and histopathological changes, using the porcine model. EVLP was performed using a flow of either 40% (n = 6), 80% (n = 6), or 100% (n = 6) of CO. No flow rate demonstrated stable 8-h EVLP. Stable 2-h EVLP was observed in all three groups. Insignificant deterioration was observed in dynamic compliance, peak airway pressure, and oxygenation between the groups. Pulmonary vascular resistance increased significantly in the 40% group (p < .05). Electrolytes demonstrated an insignificant worsening trend with longer EVLP. Interleukin-8 (IL-8) in perfusate and tissue, wet-to-dry weight ratio, and histopathological changes after EVLP were insignificantly time dependent between the groups. This study demonstrated that stable 8-h EVLP was not feasible in an open-atrium cellular model regardless of the flow of 40%, 80%, or 100% of CO. No flow was superior in terms of lung performance, lung electrolytes changes, least lung edema formation, minimal IL-8 expression in perfusate and tissue, and histopathological changes.

Ex vivo MFG-E8 treatment improves the function of lungs procured from cardiac death donors in preclinical porcine model

Ex vivo lung perfusion (EVLP) is a promising technology that allows the re-evaluation of donor lungs and has the potential to improve marginal lung reconditioning. The present study focused on the effects of milk fat globule epidermal growth factor 8 (MFG‐E8) on the function of donation after circulatory death (DCD) lungs during EVLP and transplant reperfusion. Domestic swine were assigned to 4 groups. In the control group, the donor lungs lacking warm ischemia were preserved in Perfadex for 4 h. The swine in the other three groups underwent hypoxic arrest, followed by 1 h of warm ischemia. The DCD lungs were procured and randomly divided into three groups: cold static preservation (DCD-CSP) group, DCD-EVLP group, and DCD-MFG-E8 group. The left lung of all groups was transplanted and reperfused. During EVLP and reperfusion, lung functions and pathological evaluations were performed. Treatment with MFG-E8 resulted in significantly improved blood oxygenation. The mean pulmonary artery pressure, peak airway pressure, and expression of IL-1β, IL-6, and IL-12 were significantly lower but IL-10 was higher in the DCD -MFG-E8 group. Furthermore, the lung injury severity score, pulmonary edema, and wet-to-dry weight ratio were also reduced in MFG-E8-treated lungs. However, the pulmonary vascular resistance and expression of TNF-α did not differ from the DCD -EVLP group but were significantly lower than in the DCD -CSP group. Adding MFG-E8 into the perfusate during EVLP obtains optimal graft function of lungs from DCD. This finding, if confirmed clinically, can be applied to recondition grafts and expanded use of DCD lungs.

Cost effectiveness of commercial portable exvivo lung perfusion at a low-volume US lung transplant center.

Portable exvivo lung perfusion during lung transplantation is a resource-intensive technology. In light of its increasing use, we evaluated the cost-effectiveness of exvivo lung perfusion at a low-volume lung transplant center in the USA. Patients listed for lung transplantation (2015-2021) in the United Network for Organ Sharing database were included. Quality-of-life was approximated by Karnofsky Performance Status scores 1-year post-transplant. Total transplantation encounter and 1-year follow-up costs accrued by our academic center for patients listed from 2018 to 2021 were obtained. Cost-effectiveness was calculated by evaluating the number of patients attaining various Karnofsky scores relative to cost. Of the 13 930 adult patients who underwent lung transplant in the United Network for Organ Sharing database, 13 477 (96.7%) used static cold storage and 453 (3.3%) used exvivo lung perfusion, compared to 30/58 (51.7%) and 28/58 (48.3%), respectively, at our center. Compared to static cold storage, median total costs at 1 year were higher for exvivo lung perfusion ($918 000 vs. $516 000; p = 0.007) along with the cost of living 1 year with a Karnofsky functional status of 100 after transplant ($1 290 000 vs. $841 000). In simulated scenarios, each Karnofsky-adjusted life year gained by exvivo lung perfusion was 1.00-1.72 times more expensive. Portable exvivo lung perfusion is not currently cost-effective at a low-volume transplant centers in the USA, being 1.53 times more expensive per Karnofsky-adjusted life year. Improving donor lung and/or recipient biology during exvivo lung perfusion may improve its utility for routine transplantation.

Multimodal Assessment and Intramodal Comparison of Imaging Techniques for Pediatric Pulmonary Vein Stenosis with Pulmonary Hypertension.

Pulmonary vein stenosis (PVS) is a rare, serious, and progressive disease in the pediatric population. Evaluation is complex and involves multimodality imaging. Diagnosis is important as early treatment to prevent progressive pulmonary hypertension and right ventricular dysfunction is essential. Adult studies have shown good correlation between various imaging modalities; however, there are limited data in children. This is a single-center retrospective pilot study to determine the reliability of measurement of pulmonary vein stenosis and pulmonary hypertension across different imaging modalities-computed tomography angiography (CTA), echocardiography (echo), lung perfusion scan (LPS), and cardiac catheterization (cath). PVS was defined as > 2mmHg by echo and cath and/or 50% reduction in diameter by CTA. Patients had to have an echo, CTA and cath performed within a 1-month timeframe of one another to be included in the study, with LPS data included if testing was completed at initial evaluation. Fifteen total patients were enrolled; 87% were categorized as primary PVS; a condition not directly related to direct injury or prior surgical intervention. Twenty-seven total stenotic pulmonary veins were identified (mean 1.8, range 1-4). CTA had a slightly better agreement with cath than echo in identifying PVS in different vein locations except in the LLPV. Additionally, echo and CTA had excellent sensitivity (91%) and specificity (100%) compared to cath for diagnosis of PH. We conclude that non-invasive imaging of echo and CTA has an acceptable correlation to cardiac catheterization for screening and initial evaluation of PVS and PH, as directly related to PVS, in pediatrics.

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis.

Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration. To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF. Thirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8-45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP). MP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = -0.75 and r = -0.83; p < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p < 0.01). MP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials.

Free-Breathing Functional Pulmonary Proton MRI: A Novel Approach Using Voxel-Wise Lung Ventilation (VOLVE) Assessment in Healthy Volunteers and Patients With Chronic Obstructive Pulmonary Disease.

In respiratory medicine, there is a need for sensitive measures of regional lung function that can be performed using standard imaging technology, without the need for inhaled or intravenous contrast agents. To describe VOxel-wise Lung VEntilation (VOLVE), a new method for quantifying regional lung ventilation (V) and perfusion (Q) using free-breathing proton MRI, and to evaluate VOLVE in healthy never-smokers, healthy people with smoking history, and people with chronic obstructive pulmonary disease (COPD). Prospective pilot. Twelve healthy never-smoker participants (age 30.3 ± 12.5 years, five male), four healthy participants with smoking history (>10 pack-years) (age 42.5 ± 18.3 years, one male), and 12 participants with COPD (age 62.8 ± 11.1 years, seven male). Single-slice free-breathing two-dimensional fast field echo sequence at 3 T. A novel postprocessing was developed to evaluate the MR signal changes in the lung parenchyma using a linear regression-based approach, which makes use of all the data in the time series for maximum sensitivity. V/Q-weighted maps were produced by computing the cross-correlation, lag and gradient between the respiratory/cardiac phase time course and lung parenchyma signal time courses. A comparison of histogram median and skewness values and spirometry was performed. Kruskal-Wallis tests with Dunn's multiple comparison tests to compare VOLVE metrics between groups; Spearman correlation to assess the correlation between MRI and spirometry-derived parameters; and Bland-Altman analysis and coefficient of variation to evaluate repeatability were used. A P-value <0.05 was considered significant. Significant differences between the groups were found for ventilation between healthy never-smoker and COPD groups (median XCCV, LagV, and GradV) and perfusion (median XCCQ, LagQ, and GradQ). Minimal bias and no significant differences between intravisit scans were found (P range = 0.12-0.97). This preliminary study showed that VOLVE has potential to provide metrics of function quantification. 2 TECHNICAL EFFICACY: Stage 1.

Association between pre-treatment computed tomography findings and post-treatment persistent decrease in lung perfusion blood volume

The purpose of this study was to evaluate pre-treatment CT findings in patients with acute pulmonary embolism (PE) and determine the imaging findings associated with residual hypoperfused segments in post-treatment lung perfused blood volume (LPBV). We evaluated 91 patients with acute PE who underwent dual-energy CT before and after treatment. The location of thrombi (proximal or distal) and patency of the pulmonary artery (occlusive or non-occlusive) were recorded using pre-treatment computed tomography pulmonary angiography (CTPA). Residual hypoperfusion was defined as a perfusion-decreased area seen in both the pre- and post-treatment LPBVs. The association of the location of the thrombus and vascular patency of pre-treatment CTPA with residual hypoperfusion on a segmental and patient basis was examined. In the segment-based analysis, the proportion of residual hypoperfusion in the proximal group was significantly higher than that in the peripheral group (33/125 [26.4%] vs. 9/87 [10.3%], P = 0.004). Patient-based analysis also showed that the proportion of residual hypoperfusion in patients with pre-treatment proximal thrombus was significantly higher than those without (16/42 [38.1%] vs. 3/25 (12.0%); P = 0.022). Pre-treatment vascular patency was not significantly associated with residual hypoperfusion (P > 0.05). Therefore, careful follow-up is necessary, especially in patients with proximal thrombi.