Lung Ultrasound as a Promising Diagnostic Tool for Primary Graft Dysfunction after Lung Transplantation.

PURPOSE: The aim of the study was to evaluate whether the quantification of B-lines via lung ultrasound after lung transplantation is feasible and correlates with the diagnosis of primary graft dysfunction. METHODS: Following lung transplantation, patients underwent daily lung ultrasound on postoperative days 1-3. B-lines were quantified by an ultrasound score based on the number of single and confluent B-lines per intercostal space, using a four-region protocol. The ultrasound score was correlated with the diagnosis of primary graft dysfunction. Furthermore, correlation analyses and receiver operating characteristics analyses taking into account ultrasound score, chest radiographs, and PaO2/FiO2 ratio were performed. RESULTS: A total of 32 patients (91 ultrasound measurements) were included, whereby 10 were diagnosed with primary graft dysfunction. The median B-line score was 5 [IQR: 4, 8]. There was a significant correlation between B-line score and the diagnosis of primary graft dysfunction (r = 0.59, p < 0.001). A significant correlation could also be seen between chest X-rays and primary graft dysfunction (r = 0.34, p = 0.008), but the B-line score showed superiority over chest X-rays with respect to diagnosing primary graft dysfunction in the receiver operating characteristics curves with an area under the curve value of 0.921 versus 0.708. There was a significant negative correlation between B-line score and PaO2/FiO2 ratio (r = -0.41, p < 0.001), but not between chest X-rays and PaO2/FiO2 ratio (r = -0.14, p = 0.279). CONCLUSION: The appearance of B-lines correlated well with primary graft dysfunction and outperformed chest radiographs.

Radiomic analysis of liver grafts from brain-dead donors can predict early allograft dysfunction following transplantation: a proof-of-concept study.

BACKGROUND: Selection of liver grafts suitable for transplantation (LT) mainly depends on a surgeon's subjective assessment. This study aimed to investigate the role of radiomic analysis of donor-liver CTs after brain death (DBD) to predict the occurrence of early posttransplant allograft dysfunction (EAD). METHODS: We retrospectively extracted and analyzed the left lobe radiomic features from CT scans of DBD livers in training and validation cohorts. Multivariate analysis was performed to identify predictors of EAD. RESULTS: From 126 LTs included in the study in the training cohort, 27 (21.4%) had an EAD. For each patient, 279 radiomic features were extracted of which 5 were associated with EAD (AUC = 0.81) (95% CI 0.72-0.89). Among donor and recipient clinical characteristics, cardiac arrest, steatosis on donor's CT, cold ischemic time and age of recipient were also identified as independent risk factors for EAD. Combined radiomic signature and clinical risk factors showed a strong predictive performance for EAD with a C-index of 0.90 (95% CI 0.84-0.96). A validation cohort of 23 patients confirmed these results. CONCLUSION: Radiomic signatures extracted from donor CT scan, independently or combined with clinical risk factors is an objective and accurate biomarker for prediction of EAD after LT.

Chronic lung allograft dysfunction subtype analysis by computed tomography volumetry.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation. Of the two subtypes, restrictive allograft syndrome (RAS) is characterized by a larger lung volume decrease and worse prognosis than bronchiolitis obliterans syndrome (BOS). We used computed tomography (CT) volumetry to classify CLAD subtypes and determined their clinical impact. METHODS: Adult primary lung transplants performed 2003-2015 (n = 167) were retrospectively evaluated for CLAD and subclassified with CT volumetry. Lung volume decrease of < 15% from baseline resulted in BOSCT-vol and ≥15% resulted in RASCT-vol diagnosis. Clinical impact of CLAD subtypes was defined, and the prognostic value of different lung function, radiological, and lung volume parameters present at the time of CLAD diagnosis were compared. RESULTS: CLAD affected 43% of patients and was classified with CT volumetry as BOSCT-vol in 89% and RASCT-vol in 11%. Median graft survival estimate in RASCT-vol was significantly decreased compared to BOSCT-vol (1.6 vs. 9.7 years, P = .038). At CLAD onset, RASCT-vol diagnosis (P = .05), increased lung density (P = .007), and more severe FEV1 (P = .004) decline from baseline, increased graft loss risk in multivariate analysis. CONCLUSIONS: CT volumetry serves to identify lung transplant patients with a poor clinical outcome but should be validated in prospective trials.

Quantitative Image Analysis at Chronic Lung Allograft Dysfunction Onset Predicts Mortality.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) phenotype determines prognosis and may have therapeutic implications. Despite the clarity achieved by recent consensus statement definitions, their reliance on radiologic interpretation introduces subjectivity. The Center for Computer Vision and Imaging Biomarkers at the University of California, Los Angeles (UCLA) has established protocols for chest high-resolution computed tomography (HRCT)-based computer-aided quantification of both interstitial disease and air-trapping. We applied quantitative image analysis (QIA) at CLAD onset to demonstrate radiographic phenotypes with clinical implications. METHODS: We studied 47 first bilateral lung transplant recipients at UCLA with chest HRCT performed within 90 d of CLAD onset and 47 no-CLAD control HRCTs. QIA determined the proportion of lung volume affected by interstitial disease and air-trapping in total lung capacity and residual volume images, respectively. We compared QIA scores between no-CLAD and CLAD, and between phenotypes. We also assigned radiographic phenotypes based solely on QIA, and compared their survival outcomes. RESULTS: CLAD onset HRCTs had more lung affected by the interstitial disease (P = 0.003) than no-CLAD controls. Bronchiolitis obliterans syndrome (BOS) cases had lower scores for interstitial disease as compared with probable restrictive allograft syndrome (RAS) (P < 0.0001) and mixed CLAD (P = 0.02) phenotypes. BOS cases had more air-trapping than probable RAS (P < 0.0001). Among phenotypes assigned by QIA, the relative risk of death was greatest for mixed (relative risk [RR] 11.81), followed by RAS (RR 6.27) and BOS (RR 3.15). CONCLUSIONS: Chest HRCT QIA at CLAD onset appears promising as a method for precise determination of CLAD phenotypes with survival implications.

Interobserver variability in the evaluation of primary graft dysfunction after lung transplantation: impact of radiological training and analysis of discordant cases.

PURPOSE: Radiologic criteria for the diagnosis of primary graft dysfunction (PGD) after lung transplantation are nonspecific and can lead to misinterpretation. The primary aim of our study was to assess the interobserver agreement in the evaluation of chest X-rays (CXRs) for PGD diagnosis and to establish whether a specific training could have an impact on concordance rates. Secondary aim was to analyze causes of interobserver discordances. MATERIAL AND METHODS: We retrospectively enrolled 164 patients who received bilateral lung transplantation at our institution, between February 2013 and December 2019. Three radiologists independently reviewed postoperative CXRs and classified them as suggestive or not for PGD. Two of the Raters performed a specific training before the beginning of the study. A senior thoracic radiologist subsequently analyzed all discordant cases among the Raters with the best agreement. Statistical analysis to calculate interobserver variability was percent agreement, Cohen's kappa and intraclass correlation coefficient. RESULTS: A total of 473 CXRs were evaluated. A very high concordance among the two trained Raters, 1 and 2, was found (K = 0.90, ICC = 0.90), while a poorer agreement was found in the other two pairings (Raters 1 and 3: K = 0.34, ICC = 0.40; Raters 2 and 3: K = 0.35, ICC = 0.40). The main cause of disagreement (52.4% of discordant cases) between Raters 1 and 2 was the overestimation of peribronchial thickening in the absence of unequivocal bilateral lung opacities or the incorrect assessment of unilateral alterations. CONCLUSION: To properly identify PGD, it is recommended for radiologists to receive an adequate specific training.

Color Doppler Ultrasound and Hemodynamics for Evaluating Graft Dysfunction in Recurrent Immunoglobulin A Nephropathy.

BACKGROUND The aim of this study was to investigate the diagnostic and prognostic utility of color Doppler ultrasound for graft dysfunction in recurrent immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS We selected a series of 78 biopsies diagnostic of recurrent IgAN following living-donor transplantation from July 2004 to January 2019. Based on Lee's classification, Doppler parameters in different degrees of histopathological injury were retrospectively analyzed. RESULTS The 4-year cumulative graft survival rate after biopsy was 66.3%, and the difference among the Kaplan-Meier curves of Lee's classification (P<0.01) was significant. Doppler parameters showed that echo enhancement, decreasing blood flow distribution, decreasing end-diastolic velocity (EDV) of the main renal artery (MRA), segmental renal atery (SRA) and interlobar renal artery (IRA), and an elevated resistance index (RI) of the arcuate renal artery (ARA) were significantly different among grades I-V of Lee's classification (P<0.05). Logistic multivariate analysis indicated that echo enhancement (HR 13.6, 95% CI 2.7-68.4) and decreasing EDV of the SRA (HR 1.1 for a 1-cm/s, 95% CI 1.0-1.2) were independent predictors of severe injury (IV-V). The ROC curve fitted by echo enhancement and decreasing EDV of the SRA had an area under the curve of 0.87. The cutoff was 17.5 cm/s (decreasing EDV of the SRA) without echo enhancement. The sensitivity and specificity were 72.2% and 91.7%, respectively. CONCLUSIONS Color Doppler ultrasound successfully evaluated the graft dysfunction in recurrent IgAN; a decreasing EDV of the SRA indicated severe histopathological injury and poor prognosis.

Valoración del índice de reserva de perfusión miocárdica por resonancia magnética en pacientes con trasplante cardíaco / Cardiac magnetic resonance imaging myocardial perfusion reserve index in heart transplant patients

OBJETIVO: Comparar el índice de reserva de perfusión miocárdica (IRPM) medido por resonancia magnética cardíaca de estrés (RMC-estrés) con regadenosón en sujetos trasplantados frente a no trasplantados. MATERIAL Y MÉTODOS: Se compararon, de forma retrospectiva, 20 trasplantados cardíacos consecutivos, asintomáticos y sin sospecha clínica de enfermedad microvascular, a quienes se realizó RMC-estrés con regadenosón y coronariografía por TC (CTC) para descartar enfermedad vascular del injerto (EVI) respecto a 16 sujetos no trasplantados, con RMC-estrés realizada por indicación clínica, negativa para isquemia y sin signos de cardiopatía estructural. El IRPM se estimó de forma semicuantitativa tras calcular el valor de la pendiente durante la perfusión de primer paso y dividir el valor obtenido en estrés respecto al reposo. Se comparó IRPM en ambos grupos. Los pacientes con RMC-estrés positiva para isquemia o CTC con estenosis coronaria significativa fueron derivados a coronariografía convencional. RESULTADOS: Más de la mitad de los sujetos permanecieron asintomáticos durante la prueba de estrés. La RMC-estrés resultó positiva para isquemia en dos trasplantados, que se confirmó mediante CTC y coronariografía convencional. Los pacientes trasplantados presentaron menor volumen telediastólico indexado (59,3 ±15,2 ml/m2 frente a 71,4±15,9 ml/m2, p = 0,03), menor IRPM (1,35±0,19 vs. 1,6±0,28, p = 0,003 y menor respuesta hemodinámica al regadenosón que los no trasplantados (incremento medio de la frecuencia cardíaca de 13,1±5,4 lpm frente a 28,5±8,9 lpm, p < 0,001). CONCLUSIÓN: La RMC-estrés con regadenosón es una técnica segura. En ausencia de enfermedad coronaria epicárdica significativa, los trasplantados presentan menor IRPM que los no trasplantados, lo que sugiere enfermedad microvascular. En pacientes trasplantados, la respuesta hemodinámica esperable al regadenosón es menor que en no trasplantados

OBJECTIVE: To compare the myocardial perfusion reserve index (MPRI) measured during stress cardiac magnetic resonance imaging (MRI) with regadenoson in patients with heart transplants versus in patients without heart transplants. MATERIAL AND METHODS: We retrospectively compared 20 consecutive asymptomatic heart transplant patients without suspicion of microvascular disease who underwent stress cardiac MRI with regadenoson and coronary computed tomography angiography (CTA) to rule out cardiac allograft vasculopathy versus 16 patients without transplants who underwent clinically indicated stress cardiac MRI who were negative for ischemia and had no signs of structural heart disease. We estimated MPRI semiquantitatively after calculating the up-slope of the first-pass enhancement curve and dividing the value obtained during stress by the value obtained at rest. We compared MPRI in the two groups. Patients with positive findings for ischemia on stress cardiac MRI or significant coronary stenosis on coronary CTA were referred for conventional coronary angiography. RESULTS: More than half the patients remained asymptomatic during the stress test. Stress cardiac MRI was positive for ischemia in two heart transplant patients; these findings were confirmed at coronary CTA and at conventional coronary angiography. Patients with transplants had lower end-diastolic volume index (59.3±15.2 ml/m2 vs. 71.4±15.9 ml/m2 in those without transplants, p = 0.03), lower MPRI (1.35±0.19 vs. 1.6±0.28 in those without transplants, p = 0.003), and a less pronounced hemodynamic response to regadenoson (mean increase in heart rate 13.1±5.4 bpm vs. 28.5±8.9 bpm in those without transplants, p <0.001). CONCLUSION: Stress cardiac MRI with regadenoson is safe. In the absence of epicardial coronary artery disease, patients with heart transplants have lower MPRI than patients without transplants, suggesting microvascular disease. The hemodynamic response to regadenoson is less pronounced in patients with heart transplants than in patients without heart transplants

18F-FDG PET/CT y el síndrome de intolerancia inmunológica en el injerto renal no funcionante / 18F-FDG PET/CT and non-functioning renal graft intolerance syndrome

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Can texture analysis in ultrashort echo-time MRI distinguish primary graft dysfunction from acute rejection in lung transplants? A multidimensional assessment in a mouse model.

BACKGROUND: Differentiation of early postoperative complications affects treatment options after lung transplantation. PURPOSE: To assess if texture analysis in ultrashort echo-time (UTE) MRI allows distinction of primary graft dysfunction (PGD) from acute transplant rejection (ATR) in a mouse lung transplant model. STUDY TYPE: Longitudinal. ANIMAL MODEL: Single left lung transplantation was performed in two cohorts of six mice (strain C57BL/6) receiving six syngeneic (strain C57BL/6) and six allogeneic lung transplants (strain BALB/c (H-2Kd )). FIELD STRENGTH/SEQUENCE: 4.7T small-animal MRI/eight different UTE sequences (echo times: 50-5000 µs) at three different postoperative timepoints (1, 3, and 7 days after transplantation). ASSESSMENT: Nineteen different first- and higher-order texture features were computed on multiple axial slices for each combination of UTE and timepoint (24 setups) in each mouse. Texture features were compared for transplanted (graft) and contralateral native lungs between and within syngeneic and allogeneic cohorts. Histopathology served as a reference. STATISTICAL TESTS: Nonparametric tests and correlation matrix analysis were used. RESULTS: Pathology revealed PGD in the syngeneic and ATR in the allogeneic cohort. Skewness and low-gray-level run-length features were significantly different between PGD and ATR for all investigated setups (P < 0.03). These features were significantly different between graft and native lung in ATR for most setups (minimum of 20/24 setups; all P < 0.05). The number of significantly different features between PGD and ATR increased with elapsing postoperative time. Differences in significant features were highest for an echo-time of 1500 µs. DATA CONCLUSION: Our findings suggest that texture analysis in UTE-MRI might be a tool for the differentiation of PGD and ATR in the early postoperative phase after lung transplantation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:108-116.

Case report - coronary vasospasm in transplanted heart: a puzzling phenomenon.

BACKGROUND: Coronary artery spasm (CAS) is an underdiagnosed disease especially in heart transplant patients, and in those patients the etiology and pathophysiology remain largely unknown, although it has been associated with cardiac allograft vasculopathy or graft rejection. CASE PRESENTATION: We report the case of a heart-transplant patient whose cardiac graft experienced two coronary vasospasms: the first before transplantation, and the other at one-month of a postoperative course complicated by primary graft failure. CONCLUSION: Our case illustrates that a transplanted heart predisposed with coronary vasospasm may suffer from early relapse in the recipient despite of complete post-surgical autonomic denervation. Exacerbated endothelial dysfunction of the donor heart after transplant, with the addition of systemic factors in the recipient may be involved in the genesis of this puzzling phenomenon.

Interobserver variability impairs radiologic grading of primary graft dysfunction after lung transplantation.

OBJECTIVES: The current score for primary graft dysfunction after lung transplantation relies heavily on chest radiographs, and radiologic judgment can make the difference between the lowest (primary graft dysfunction 0) and the highest (primary graft dysfunction 3) grade. This study aimed to evaluate interobserver variability of the scoring of postoperative chest radiographs and its impact on primary graft dysfunction grades in a large single-center cohort. METHODS: We retrospectively analyzed 497 lung transplantations performed between January 2010 and July 2016 at the Medical University of Vienna. Five trained thoracic radiologists were asked to independently examine postoperative chest radiographs performed at 0 to 6 hours, 24 hours, 48 hours, and 72 hours after arrival at the intensive care unit. Interobserver variability was calculated using Fleiss' kappa (κ) statistics. RESULTS: A total of 1988 chest radiographs were evaluated. Consensus among all 5 radiologists was found in only 826 cases (43.0%). At 0 to 6 hours and 24 hours, only a moderate agreement was found among the 5 radiologists (κ = 0.456 and 0.456, respectively), and agreement was even worse at 48 and 72 hours (κ = 0.405 and κ = 0.409). On the basis of this high interobserver variability, best and worst case scenarios were calculated leading to primary graft dysfunction 3 rates of 8.4% versus 28.4% at 0 to 6 hours, 1.8% versus 4.8% at 24 hours, 2.0% versus 5.3% at 48 hours, and 0.2% versus 3.1% at 72 hours. A high recipient body mass index and size-reduced transplants were found to be factors associated with higher rates of interobserver variability. CONCLUSIONS: The substantial interobserver variability found in this retrospective analysis underlines the difficulty to adequately grade post-transplant organ function. Future revisions of the primary graft dysfunction grading should take this problem into consideration.

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.

Positional ischaemia of transplant kidney: A rare cause of early graft dysfunction.

Kinking of the kidney transplant vessels late after the operation is a rare complication that can lead to significant morbidity and mortality. We present a case of positional ischemia of the renal allograft resulting from dynamic and positional kinking of the graft vasculature, which was diagnosed by ultrasonography with the patient standing. The graft was repositioned into the sub-rectus pocket and the ischaemic injury resolved.

Inflammation and primary graft dysfunction after lung transplantation: CT-PET findings.

BACKGROUND: The leading cause of early mortality after lung transplantation is Primary graft dysfunction (PGD). We assessed the lung inflammation, inflation status and inhomogeneities after lung transplantation. Our purpose was to investigate the possible differences between patients who did or did not develop PGD. METHODS: We designed a prospective observational study enrolling patients who underwent a CT-PET study within 1 week after lung transplantation. Twenty-four patients (10 after double- and 14 after single-lung) were enrolled. Respiratory and hemodynamic data were collected before, during and after lung transplantation. Each patient underwent computed tomography-positron emission tomography (CT-PET) scan early after surgery. Broncho-alveolar lavage (BAL) fluid collection was performed to analyze inflammatory mediators. RESULTS: The grafts showed a [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake rate of 26[18-33]*10-4 mLblood/mLtissue/min (reference values 11[7-15]*10-4). Three double- and six single-lung recipients developed PGD. The grafts of patients who developed PGD had similar [18F]FDG uptake than grafts of patients who did not (28[18-26]*10-4 versus 26[22-31]*10-4, P=0.79). Not-inflated tissue fraction was significantly higher (28[20-38]% versus 14[7-21]%, P=0.01) while well-inflated fraction was significantly lower (29[25-41]% versus 53[39-65]%, P<0.01). Inhomogeneity extent was higher in patients who developed PGD (23[18-26]% versus 14[10-20]%, P=0.01)The lung weight was 650[591-820]g versus 597[480-650]g (P=0.09)). BAL fluid analysis for inflammatory mediators did not detect a difference between the study groups. CONCLUSIONS: Compared to healthy lungs, all the grafts showed increased [18F]FDG uptake rate, but there were no differences between patients who developed PGD and patients who did not. Of note, the PGD patients showed a worse inflation status of lungs and a higher inhomogeneity extent.

Quantitative chest CT for subtyping chronic lung allograft dysfunction and its association with survival.

Chronic lung allograft dysfunction (CLAD) is a major cause of mortality in lung transplant recipients. CLAD can be sub-divided into at least 2 subtypes with distinct mortality risk characteristics: restrictive allograft syndrome (RAS), which demonstrates increased overall computed tomography (CT) lung density in contrast with bronchiolitis obliterans syndrome (BOS), which demonstrates reduced overall CT lung density. This study aimed to evaluate a reader-independent quantitative density metric (QDM) derived from CT histograms to associate with CLAD survival. A retrospective study evaluated CT scans corresponding to CLAD onset using pulmonary function tests in 74 patients (23 RAS, 51 BOS). Two different QDM values (QDM1 and QDM2) were calculated using CT lung density histograms. Calculation of QDM1 includes the extreme edges of the histogram. Calculation of QDM2 includes the central region of the histogram. Kaplan-Meier analysis and Cox regression analysis were used for CLAD prognosis. Higher QDM values were significantly associated with decreased survival. The hazard ratio for death was 3.2 times higher at the 75th percentile compared to the 25th percentile using QDM1 in a univariate model. QDM may associate with CLAD patient prognosis.

Salvage of Pancreas Transplant After Successful Splenic Artery Thrombectomy.

Primary nonfunction due to thrombosis after pancreas transplant is still the leading cause of nonimmunologic graft failure. Early identification of pancreatic graft arterial thrombus and prompt surgical intervention are effective for rescue of graft perfusion and its associated complications. Here, we report a case of successful surgical thrombectomy of the splenic artery, with particular emphasis on clinical presentation, diagnosis, and surgical technique.

Multivariate modeling using quantitative CT metrics may improve accuracy of diagnosis of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: To assess how quantitative CT (qCT) metrics compare to pulmonary function testing (PFT) and semi-quantitative image scores (SQS) to diagnose bronchiolitis obliterans syndrome (BOS), manifestation of chronic lung allograft dysfunction after lung transplantation (LTx), according to the type of LTx (unilateral or bilateral). METHODS: Paired inspiratory-expiratory CT scans and PFTs of 176 LTx patients were analyzed retrospectively, and separated into BOS (78) and non-BOS (98) cohorts. SQS were assessed by 2 radiologists and graded (0-3) for features including mosaic attenuation and bronchiectasis. qCT metrics included lung volumes and air trapping volumes. Multivariate logistic regression (MVLR) and support vector machines (SVM) were used for the classification task. RESULTS: MVLR and SVM models using PFT metrics demonstrated highest accuracy for bilateral LTx (max AUC 0.771), whereas models using qCT metrics-only outperformed models using SQS or PFTs in unilateral LTx (max AUC 0.817), to diagnose BOS. Adding PC (principal components) from qCT on top of PFT improved model diagnostic accuracy for all transplant types. CONCLUSIONS: Combinations of qCT metrics augment the diagnostic performance of PFTs, are superior to SQS to predict BOS status, and outperform PFTs in the unilateral LTx group. This suggests that latent information on paired volumetric CT may allow early diagnosis of BOS in LTx patients, particularly in unilateral LTx.

The role of biomechanical anatomical modeling via computed tomography for identification of restrictive allograft syndrome.

Chronic lung allograft dysfunction (CLAD) reduces long-term graft survival. It is important to distinguish CLAD subtypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) as RAS has a worse prognosis and accurate subtyping could facilitate targeted treatments. However, the current diagnosis of CLAD subtypes is based on pulmonary function test (PFT) results that reflect global estimates of lung function; anatomical modeling based on computed tomography (CT) has the potential to provide detailed analysis of global and regional lung function. The purpose of this study is to evaluate the utility of CT-based anatomical modeling for the identification of RAS. This retrospective study included 51 patients (CLAD: 17 BOS and 17 RAS, control: 17 No-CLAD). CT data were assessed using a biomechanical model-based platform (MORFEUS) to characterize changes in lung deformation between baseline and disease onset. Lung deformation demonstrated high sensitivity and specificity (>80%) in differentiating RAS from BOS (P<.0001) and No-CLAD (P<.0001). There were matching radiological reading and inward deformation abnormalities in 79% of lung sections in patients with RAS. Anatomical modeling is complementary to conventional assessment in the diagnosis of RAS and potentially provides quantitative data that can help in the characterization and detailed assessment of heterogeneous lung parenchymal disease.

CT at onset of chronic lung allograft dysfunction in lung transplant patients predicts development of the restrictive phenotype and survival.

PURPOSE: To describe early signs for restrictive subtype of chronic lung allograft dysfunction (CLAD) after lung transplantation in computed tomography (CT) and to evaluate the predictive value for disease progression and survival. MATERIAL AND METHODS: 52 CT examinations in lung transplant patients at CLAD onset were scored for CT features referring to airways disease, parenchymal or pleural abnormality. Patients with and without later development of restrictive CLAD (TLC≤80%) were compared. A radiological score for inflammation including pleural effusion, central and peripheral ground glass opacities and consolidations was calculated and used for survival analysis. RESULTS: CT of patients with later development of restrictive CLAD showed significantly more often abnormalities at CLAD onset, in particular consolidations (57% vs. 4%; p<0.001) and ground glass attenuations (71% vs. 7%; p<0.001) than those of patients without the restrictive phenotype. CT score for inflammation was significantly higher in patients with than without later restrictive CLAD (3.4 vs. 0.6; p<0.001). Survival of patients with a high score (>2) for inflammation in CT at CLAD onset was significantly lower than of those with a low score (443 vs. 2415 days; p=0.019). CONCLUSIONS: CT at CLAD onset differs in patients with/without later development of the restrictive phenotype. It is therefore an indicator for future development of restrictive CLAD and predictor for survival. It should be implemented in the diagnostic work-up at diagnosis of CLAD.