Fully automated analysis combining [18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression.

PURPOSE: To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. MATERIAL AND METHODS: At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier's performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. RESULTS: In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77-0.93 (sensitivity 0.91, 95% CI 0.81-0.97; specificity 0.71, 95% CI 0.44-0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72-0.9), 0.81 for [18F]-FET-PET (95% CI 0.7-0.89), and 0.81 for expert consensus (95% CI 0.7-0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. CONCLUSION: Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.

Contrast-enhanced ultrasound (CEUS) prediction of focal liver lesions in patients after liver transplantation in comparison to histopathology results.

PURPOSE: To investigate the value of contrast-enhanced ultrasound (CEUS) in histologic prediction of focal liver lesions after liver transplantation. MATERIALS AND METHODS: 10 focal liver lesions in 10 patients after liver transplantation were scanned using CEUS and the CEUS results were compared with the histopathological results. RESULTS: Among 10 focal liver lesions, 7 proofed to be histopathological benign and 3 lesions proofed to be histopathological malignant. All lesions (100%) were correctly report as benign or malignant in the report of the CEUS examination. CONCLUSION: CEUS can be helpful in the differentiation of benign and malignant focal liver lesions in patients after liver transplantation and can be used in clinical management of focal liver lesions.

Diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in monitoring vascular complications in patients after liver transplantation - diagnostic performance compared with histopathological results.

PURPOSE: To analyse the diagnostic performance of contrast-enhanced ultrasound (CEUS) in patients with vascular complications and transplant rejection compared to histopathological results. MATERIALS AND METHODS: Our study consisted of 45 retrospectively analysed patients that underwent liver transplantations between January 1993 and December 2015 and developed post-transplant vascular complications with transplant rejection. CEUS examinations took place between September 2006 and December 2015. CEUS findings were correlated with histopathological results. RESULTS: CEUS showed a sensitivity of 61.5%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0% and a negative predictive value (NPV) of 86,5% in the detection of vascular complications with post-transplant rejection. 5 examinations were reported as normal whereas the histopathological result showed a transplant rejection (false-negative). CONCLUSION: CEUS might be a useful additional non-invasive technique for the assessment of vascular complications with post-transplant rejection in patients after liver transplantation.

Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients.

PURPOSE: To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). METHODS: We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. RESULTS: The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. CONCLUSIONS: Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors.

Robust evidence for long-term survival with 90Y radioembolization in chemorefractory liver-predominant metastatic colorectal cancer.

OBJECTIVES: Our aim was to provide further evidence for the efficacy/safety of radioembolization using yttrium-90-resin microspheres for unresectable chemorefractory liver metastases from colorectal cancer (mCRC). METHODS: We followed 104 consecutively treated patients until death. Overall survival (OS) was calculated from the day of the first radioembolization procedure. Response was defined by changes in tumour volume as defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 and/or a ≥30 % reduction in serum carcinoembryonic antigen (CEA) at 3 months. RESULTS: Survival varied between 23 months in patients who had a complete response to prior chemotherapy and 13 months in patients with a partial response or stable disease. Median OS also significantly improved (from 5.8 months to 17.1 months) if response durability to radioembolization extended beyond 6 months. Patients with a positive trend in CEA serum levels (≥30 % reduction) at 3 months post-radioembolization also had a survival advantage compared with those who did not: 15.0 vs 6.7 months. Radioembolization was well tolerated. Grade 3 increases in bilirubin were reported in 5.0 % of patients at 3 months postprocedure. CONCLUSIONS: After multiple chemotherapies, many patients still have a good performance status and are eligible for radioembolization. This single procedure can achieve meaningful survivals and is generally well tolerated. KEY POINTS: • After multiple chemotherapies, many patients are still eligible for radioembolization (RE). • RE can achieve meaningful survival in patients with chemorefractory liver-predominant metastatic colorectal cancer (mCRC). • Tumour responsiveness to prior systemic treatments is a significant determinant of overall survival (OS) after RE. • Radioembolization in patients with a good performance status is generally well tolerated.

Malignancies after liver transplantation: Value of contrast-enhanced ultrasound (CEUS).

PURPOSE: To evaluate the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and computed tomography (CT) in the diagnosis of malignancies after liver transplantation. MATERIALS AND METHODS: A total of 23 patients with suspicious liver masses after liver transplantation with initial imaging series between September 2006 and September 2015 were statistically analysed. CEUS and CT were compared in their diagnosis of malignancy with CT being the gold standard. Out of 23 patients 9 patients showed malignant masses in CT, which could also be detected in 7 out 9 of cases using CEUS. RESULTS: CEUS showed a sensitivity of 77.8%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0% and a negative predictive value (NPV) of 87,5% in comparison with CT being the gold standard. In 2 cases CT showed a malignancy, contrary to the CEUS examination that was reported as normal. CONCLUSION: CEUS seems to be an alternative option for the evaluation of malignant masses in liver transplant patients. CEUS shows a high specificity and PPV in the detection of malignant liver masses.

Vascular complications in liver transplantation: Beneficial role of contrast-enhanced ultrasound (CEUS) in the postoperative phase.

PURPOSE: To compare the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and computed tomography (CT) in the diagnosis of vascular complications after liver transplantation in the postoperative phase. MATERIALS AND METHODS: A total of 60 patients with elevated liver function tests after liver transplantation with initial imaging studies between July 2005 and November 2015 were retrospectively analysed. CEUS and CT were compared in their diagnosis of vascular complications and CT was considered as the gold standard. Out of 60 patients 28 patients showed vascular complications in CT, which could also be detected in 25 out 28 of cases using CEUS. Diagnostic accuracy was tested by using the CT diagnosis as the gold standard. RESULTS: CEUS showed a sensitivity of 89.3%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0% and a negative predictive value (NPV) of 91,4% compared to CT as the gold standard. In 3 cases CT showed a vascular complication, whereas the CEUS examination was reported as normal. CONCLUSION: CEUS is a fast, non-ionizing imaging modality for the initial exclusion of vascular complications after liver transplantation. CEUS shows a high specificity and PPV in the detection of vascular complications. In unclear cases CT still is considered as the gold standard.

MRI and contrast enhanced ultrasound (CEUS) image fusion of renal lesions.

Ultrasound is a common and established imaging method for the initial characterization of renal lesions. The widespread used Bosniak classification (I-IV) classifies renal lesions in five individual groups using contrast-enhanced computer tomography (CE-CT), magnetic resonance imaging (MRI) and/or contrast-enhanced ultrasound (CEUS) imaging criteria. For complex pathologies, CEUS/MRI image fusion is a novel imaging technique for the differentiation of benign and malignant renal lesions. Compared to CE-CT and MRI alone, ultrasound image fusion offers the additional possibility of being a real-time imaging technique that can be used together with other cross-sectional imaging techniques.This article describes the newest possibilities of image fusion with CEUS and MRI in detection and characterization of unclear renal lesions.

Feasability of contrast-enhanced ultrasound with image fusion of CEUS and MS-CT for endovascular grafting in infrarenal abdominal aortic aneurysm in a single patient.

Currently methods to reduce radiation and contrast media application in endovascular repair of aortic aneurysms (EVAR) are investigated. First positive results for real-time contrast medium-enhanced ultrasonography (CEUS) guided endovascular aortic repair have been reported. A combination with image fusion of CEUS and preoperative multi-slice computed tomography (MS-CT) might offer added safety regarding stent-graft positioning and sealing of the landing zones.EVAR was performed in a patient with an asymptomatic infrarenal aortic aneurysm and a penetrating aortic ulcer in the neck region. The precise placement of the stent-graft was performed with CEUS using image fusion and native intraprocedural angiographic fluoroscopy and confirmed with digital subtraction angiography (DSA) using iondinated contrast media. At follow-up, CEUS was used to exclude endoleaks and stent-graft failure or malposition.The precise CEUS-guided placement of the stent-graft was technically successful. No artifacts due to electrical noise and metallic parts of the operating table and surgical instruments occurred. The amount of iodinated contrast media was reduced as intraoperative follow-up was performed using CEUS.CEUS with image fusion combined with intraprocedural angiographic fluoroscopy enables accurate stent-graft placement without use of any nephrotoxic contrast media. This allows EVAR in patients with renal insufficiency or allergic reactions to contrast media.

Evaluation of multimodality imaging using image fusion with MRI and CEUS in an experimental animal model.

PURPOSE: To evaluate the diagnostic benefits of multimodality imaging using image fusion with magnetic-resonance-imaging (MRI) and contrast-enhanced-ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model for the assessment of tissue hemodynamics and morphology. MATERIAL AND METHODS: Human hypopharynx-carcinoma-cells were injected subcutaneously into the left flank of 15 female athymic nude rats. After 10 daysof subcutaneous tumor growth, CEUS and MRI measurements were performed using a high-end-ultrasound-system and 3-T-MRI. After successful point-to-point or plan registration, the registered MR-images were simultaneously shown with the respective ultrasound sectional plane. Data evaluation was performed using the digitally stored video sequence data sets by two experienced radiologists using a subjective 5-point scale. RESULTS: CEUS and MRI are well-known techniques for the assessment of tissue hemodynamics (score: mean 3.8 ± 0.4 SD and score 3.8 ± 0.4 SD). Real-time image fusion of MRI and CEUS yielded a significant (p <  0.001) improvement in score (score 4.8 ± 0.4 SD). Reliable detection of small necrotic areas was possible in all animals with necrotic tumors. No significant intraobserver and interobserver variability was detected (kappa coefficient = +1). CONCLUSION: Image fusion of MRI and CEUS gives a significant improvement for reliable differentiation between different tumor tissue areas and simplifies investigations by showing the morphology as well as surrounding macro-/microvascularization.

Safety of Radioembolization with (90)Yttrium Resin Microspheres Depending on Coiling or No-Coiling of Aberrant/High-Risk Vessels.

PURPOSE: To evaluate the safety of radioembolization (RE) with (90)Yttrium ((90)Y) resin microspheres depending on coiling or no-coiling of aberrant/high-risk vessels. MATERIALS AND METHODS: Early and late toxicity after 566 RE procedures were analyzed retrospectively in accordance with the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v3.0). For optimal safety, aberrant vessels were either coil embolized (n = 240/566, coiling group) or a more peripheral position of the catheter tip was chosen to treat right or left liver lobes (n = 326/566, no-coiling group). RESULTS: Clinically relevant late toxicities (≥ Grade 3) were observed in 1% of our overall cohort. The no-coiling group had significantly less "any" (P = 0.0001) or "clinically relevant" (P = 0.0003) early toxicity. There was no significant difference (P > 0.05) in delayed toxicity in the coiling versus the no-coiling group. No RE-induced liver disease was noted after all 566 procedures. CONCLUSION: RE with (90)Y resin microspheres is a safe and effective treatment option. Performing RE without coil embolization of aberrant vessels prior to treatment could be an alternative for experienced centers.