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The 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has the potential of a noninvasive method for lung allograft rejection (AR) detection, but the accuracy is unsatisfied. Radiomics has been shown to improve the accuracy of diagnosis and treatment response assessment in other fields. Using a rat model of lung transplantation (LTx), we aim to assess the correlation between 18F-FDG PET-based radiomics and lung AR, and compare the predictive power to standardized uptake values (SUVs). Twenty-eight rats were included in three groups at week 3 (Syngeneic, Immunosuppression and AR) and four groups (Syngeneic, Immunosuppression, Hybrid and AR) at week 6. The PyRadiomics package was used to extract the radiomic features from the PET images. The least absolute shrinkage and selection operator (LASSO) algorithm was used to establish the AR-related radiomics signature. A radiomics signature-based nomogram was created to visualize the outcome prediction. We compared the predictive performance of the radiomics signature and SUVs using the area under the receiver operator characteristic curve (AUC). Histopathology results served as a reference. From the PET images, a total of 110 radiomic features were extracted, and most of the radiomic features had an acceptable correlation with the histopathological results (P < 0.05). The radiomics signature score, based on five AR-related radiomic features, showed a tremendous positive correlation with A grade rejection, B grade rejection, and percentage of lung parenchyma with coefficients of 0.813, 0.827, and 0.746, respectively (P < 0.001). There was an apparent decline between week 3 and week 6 in the Hybrid group, although these changes did not achieve statistical significance (P = 0.052). The radiomics nomogram illustrated an acceptable agreement for AR detection. The radiomics signature had better discrimination and better predictive power than SUV max and SUV mean (AUC=0.944 versus 0.839 and 0.861, respectively). The 18F-FDG PET-based radiomics is a potential noninvasive and accurate method to predict lung AR in a rat model of an orthotopic LTx. The radiomics signature showed a better predictive power than SUVs. [ABSTRACT FROM AUTHOR]

Purpose Ex vivo lung perfusion (EVLP) enables novel therapeutic approaches to repair damaged lungs for transplantation. We investigated the concept and feasibility of elective cell therapy for donor lungs. Dosing, efficacy and transgene expression kinetics of engineered mesenchymal stromal cell therapy were examined in pig EVLP and transplantation. Methods Human umbilical cord perivascular mesenchymal stromal/stem cells were transduced with an adenoviral vector encoding human IL-10 (MSC-hIL-10 cells), cryopreserved and recovered 1h before use. Pig lungs with 4 to 24-hour cold ischemia (n=5) were connected to EVLP for 6 (n=3) or 12 hours (n=2) and MSC-hIL-10 cells (40-150 × 106) were administered through the pulmonary artery after 1h of EVLP. Left single lung transplantation was performed after EVLP and the grafts were monitored up to 4h (n=4) and 3d (n=1) after reperfusion. Human IL-10 levels were determined by ELISA and fluorescence in situ hybridization with human-specific ALU probes was used to track MSC-hIL-10 cells. Results Supra-therapeutic levels of hIL-10 were present in EVLP perfusate within minutes after MSC-hIL10 cell administration and the levels consistently increased during EVLP (Figure 1A). Recipient plasma hIL-10 levels were elevated 1h after lung transplantation, remained high for 4h and gradually decreased to low levels by 3d after transplantation (Figure 1C). Elevated tissue and bronchoalveolar lavage hIL-10 levels were observed in the transplanted lung and remained low in the recipient native lung. MSC-hIL-10 cells were detected in the donor lung during EVLP and after transplantation (Figure 1B). Conclusion Engineered mesenchymal stromal cell therapy during EVLP is a novel and practical "off-the-shelf" strategy to achieve rapid transient therapeutic levels of soluble cytokines such as IL-10 for pre-transplant lung repair and protection. Ongoing studies will determine the therapeutic effect and longer-term fate of MSC-hIL-10 cells delivered during EVLP. [ABSTRACT FROM AUTHOR]

Ex-vivo lung perfusion (EVLP) maintains marginal donor lungs at body temperature with ventilation and circulating perfusate, allowing for functional assessment prior to transplantation. Prolonged EVLP would allow for advanced time-dependent therapies for donor lung repair and reconditioning. We hypothesized that the addition of a dialysis machine to the EVLP circuit would maintain homeostasis of the donor lung and prolong EVLP duration. Porcine donor lungs (n=3) were extracted and placed on the EVLP platform for 36 hours or until termination criteria (dynamic compliance < 15ml/cmH 2 O) was reached. Lungs were perfused with an acellular solution and closed atrium, according to the Toronto protocol. A dialysis machine was incorporated into the EVLP circuit with a custom-designed dialysate to continuously dialyze perfusate using continuous venovenous hemodialysis (Fig1A). Physiological function, electrolytes and inflammatory mediators in EVLP perfusate were measured hourly. In this pilot study, dialysis cases were compared to historical controls with similar protocol (n=6). Dialysis successfully prevented an increase in electrolyte levels (Fig 1C) and maintained glucose and lactate levels at baseline (1C). EVLP was prolonged in the dialysis group with a mean duration of EVLP reaching 32±6.93 h in the E+D group compared to 18.67±3.27 h in the historical control group (Fig 1D). Percent lung survival at 24h of perfusion was 100% in the E+D group, while only 20% was seen in historical controls (Fig 1B). Both lungs which survived to 36h of EVLP presented excellent lung function based on assessment by EVLP. Dialysis may preserve lung function and length of EVLP by maintaining homeostasis of the lung. Following the results of this encouraging pilot study, a formal blinded experiment is being performed and is underway. [ABSTRACT FROM AUTHOR]

Ex-vivo lung perfusion (EVLP) maintains marginal donor lungs at body temperature with ventilation and circulating perfusate, allowing for functional assessment prior to transplantation. Prolonged EVLP would allow for advanced time-dependent therapies for donor lung repair and reconditioning. We hypothesized that the addition of a dialysis machine to the EVLP circuit (dEVLP) would maintain homeostasis of the donor lung and prolong EVLP duration. Porcine donor lungs (n=6) were extracted and placed on the EVLP platform for 36 hours or until termination criteria (dynamic compliance < 15ml/cmH 2 O) was reached. Lungs were perfused with an acellular solution and closed atrium, according to the Toronto protocol. A dialysis machine was incorporated into the EVLP circuit with a custom-designed dialysate to continuously dialyze perfusate using continuous venovenous hemodialysis (Fig1A). Physiological function, electrolytes and inflammatory mediators in EVLP perfusate were measured hourly. In this proof of concept study, dialysis cases were compared to historical controls with similar protocol (n=5). EVLP was prolonged in the dialysis group with a mean duration of EVLP reaching 30.83±0.57 h in the dEVLP group compared to 19.6±2.61 h in the historical control group (Fig 1D). Percent lung survival at 24h of perfusion was 100% in the dEVLP group, while only 20% was seen in historical controls (Fig 1B). Dialysis successfully prevented an increase in electrolyte levels (Fig 1C), maintained glucose and lactate levels at baseline (1C), and maintained physiological parameters (Fig 1D). Both lungs which survived to 36h of EVLP presented excellent lung function based on assessment by EVLP. Dialysis may preserve lung function and length of EVLP by maintaining homeostasis of the lung. Following the results of this encouraging proof of concept study, a formal blinded experiment is underway. [ABSTRACT FROM AUTHOR]