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Haemoglobin expression is not restricted to erythroid cells. We investigated the gene expression of the haemoglobin subunits haemoglobin, alpha adult chain 1 (Hba-a1) and haemoglobin, beta (Hbb), 2,3-bisphosphoglycerate mutase (Bpgm) and the oxygen-regulated genes BCL2/adenovirus E1B interacting protein 3 (Bnip3), solute carrier family 2 (facilitated glucose transporter), member 1 (Slc2a1) and N-myc downstream regulated gene 1 (Ndrg1) in the murine preimplantation embryo, comparing invivo to invitro gene expression. Relatively high levels of Hba-a1 and Hbb were expressed invivo from the 2-cell to blastocyst stage; in contrast, little or no expression occurred invitro. We hypothesised that the presence of haemoglobin invivo creates a low oxygen environment to induce oxygen-regulated gene expression, supported by high expression of Slc2a1 and Ndrg1 in invivo relative to invitro embryos. In addition, analysis of an invitro-derived human embryo gene expression public dataset revealed low expression of haemoglobin subunit alpha (HBA) and HBB, and high expression of BPGM. To explore whether there was a developmental stage-specific effect of haemoglobin, we added exogenous haemoglobin either up to the 4-cell stage or throughout development to the blastocyst stage, but observed no difference in blastocyst rate or the inner cell mass to trophectoderm cell ratio. We conclude that haemoglobin in the invivo preimplantation embryo raises an interesting premise of potential mechanisms for oxygen regulation, which may influence oxygen-regulated gene expression.

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Blastocoel expansion during embryo development is known to be reliant on the Na+/K+-ATPase pump, but little is known about the relative contribution of active (Na+/K+-ATPase pump) and facilitated diffusion (aquaporins) water transport during blastocoel re-expansion after vitrification. The aims of this study were to examine potential effects of artificial blastocoel collapse (ABC) on markers of embryo stress and the contribution of active and facilitated diffusion water transport mechanisms to blastocoel re-expansion. Day 5 mouse embryos were vitrified using either a standard protocol, laser pulse ABC, a hyperosmotic sucrose ABC protocol or both laser pulse and sucrose. Using real-time polymerase chain reaction, no differences were found in the gene expression of the endoplasmic reticulum (ER) stress markers activating transcription factor 4 (Atf4) or heat shock protein 90-alpha (Hsp90α) 2h after warming. Similarly, expression of the Na+/K+-ATPase pump gene, ATPase, Na+/K+ transporting, beta 1 polypeptide (Atp1b1) and protein did not differ between groups. Aquaporin 8 (Aqp8) gene expression was significantly lower in the laser+sucrose ABC group than in fresh controls, and aquaporin 3 (Aqp3) expression significantly higher in standard vitrified embryos compared with all other groups. Ouabain, a potent and specific Na+/K+-ATPase pump inhibitor, inhibited blastocoel re-expansion in both standard protocol- and laser ABC-vitrified embryos, reducing both groups to the same rate of re-expansion 3h after warming. These results demonstrate that ABC before vitrification does not alter mRNA or protein expression of Na+/K+-ATPase, or mRNA levels of ER stress genes Atf4 and Hsp90α. Activity of the pump may be increased in ABC embryos, with potential compensation by AQP3 when it is compromised.

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New clinical and technological advances in the field of magnetic resonance imaging (MRI) and targeted image-guided biopsy techniques have significantly improved the detection, localization and staging as well as active surveillance of prostate cancer in recent years. Multiparametric MRI (mpMRI) is currently the main imaging technique for the detection, characterization and diagnostics of metastasizing prostate cancer and is of high diagnostic importance for local staging within the framework of the detection of prostate cancer.

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Primary prostatic sarcomas are rare, reportedly comprising less than 1% of all prostate malignancies. Most patients present with lower urinary tract symptoms due to bladder outlet obstruction. Prostate-specific antigen (PSA) is typically normal. Histological confirmation and staging by a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis and abdomen are essential for diagnosis and treatment planning. The differential diagnosis includes sarcomatoid prostate cancer or benign spindle cell tumors. Primary prostatic sarcomas are often aggressive and require multimodal treatment with surgery and (neo)adjuvant radiation and/or chemotherapy. The risk of local recurrence is high and the long-term prognosis is poor.

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Lymphangiomas are a rare condition, which are characterized by multiple cystic lesions of a single or multiple organs that are thought to originate from intrauterine atypically distended and connected lymphatic tissue. We describe a case of a 56 years old woman with the final diagnosis of a perinephric lymphangioma. With the use of contrast-enhanced ultrasound (CEUS) it was possible to add valuable diagnostic information regarding the extent of the lymphangioma to surrounding tissue without the necessity to use additional ionizing radiation or nephrotoxic contrast agents.

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OBJECTIVES: To evaluate the usage of different guidelines and to estimate the impact of changed recommendation in routine management, therapy and follow-up of patients with renal cell cancer (RCC). METHODS: An anonymous questionnaire was sent to 600 urologists in Germany. Twenty-seven percent of them were included in the analysis. The questions were about the practice setting, surgical and medical treatment of RCC, follow-up modalities, knowledge and usage of RCC guidelines. Results were correlated with the recommendations of the EAU-guideline. RESULTS: Sixty-eight percent of the urologists were office based. Sixty percent were located in bigger cities. Ninety-eight percent of the colleagues reported to be knowledgeable about the EAU-guidelines, 62% reported to know the American Urological Association, 59% DGU/AWMF, 19% National Comprehensive Cancer Network, 19% European Society for Medical Oncology, 13% Onkopedia, and 3% British Association of Urological Surgeons-guidelines. Eighty-seven percent reported that partial nephrectomy (Nx) was performed in tumours with diameter <4 cm. Forty-one percent performed a radical Nx for tumours that were 4-7 cm. Follow-up of RCC was done in 99%. Fifty-nine percent underwent an abdominal CT scan after 6 months. Thirty-nine percent got a chest X-ray done. Among those with metastatic RCC, only 84% were offered systemic therapy. First-line therapy was predominantly advocated using sunitinib. CONCLUSION: Almost all urologists know and use the EAU-guidelines. Other guidelines are rarely used. Follow-up is performed in discordance with the EAU-recommendations. Interestingly, only 84% with metastatic disease are introduced to systemic therapy.

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INTRODUCTION: Shear wave elastography (SWE) and its derivative Supersonic Shear Imaging (SSI) are newer techniques for the determination of tissue elasticity by measuring the velocity of generated shear waves (SWV), which correlates positively with tissue stiffness.The techniques are integrated into many modern ultrasound systems and have been examined in the evaluation of viscoelastic properties of different organ systems. Two-dimensional shear wave elastography (2D SWE) of the testes has been found to be a useful tool in recent studies which included the determination of standard values in healthy volunteers. Three-dimensional shear wave elastography (3D SWE) is the latest development in elastography and is made possible by generation of a multiplanar three-dimensional map via volumetric acquisition with a special ultrasound transducer. This technique allows the assessment of tissue elasticity in a three-dimensional, fully accessible organ map.The aim of this preliminary study was to both evaluate the feasibility of 3D SWE and to compare 2D and 3D SWE standard values in the testes of healthy subjects. MATERIAL AND METHODS: We examined the testes of healthy male volunteers (n = 32) with a mean age of 51.06±17.75 years (range 25-77 years) by B-mode ultrasound, 2D and 3D SWE techniques in September of 2016. Volunteers with a history of testicular pathologies were excluded. For all imaging procedures the SL15-4 linear transducer (bandwidth 4-15 MHz) as well as the SLV16-4 volumetric probe (bandwidth 4-16 MHz) of the Aixplorer® ultrasound device (SuperSonic Imagine, Aix-en-Provence, France) were used. Seven regions of interest (ROI, Q-Box®) within the testes were evaluated for SWV using both procedures. SWV values were described in m/s. Results were statistically evaluated using univariateanalysis. RESULTS: Mean SWV values were 1.05 m/s for the 2D SWE and 1.12 m/s for the 3D SWE.Comparisons of local areas delivered no statistically significant differences (p = 0.11 to p = 0.66), except for the region in the central portion in the superior part of the coronal plane (p = 0.03). Testicular volume was significanty higher by a mean of 1.72 ml when measured with 3D SWE (p = 0.001). CONCLUSION: 3D SWE proved to be a feasible diagnostic tool in the assessment of testicular tissue, providing the examiner with a fully accessible three-dimensional map in a multiplanar or multislice view. With this technique a more precise testicular imaging - especially if combined with the display of tissue stiffness in SWE - is available and therefore could improve the diagnostic work-up of scrotal masses or the routine investigation of infertile men. Further studies for a better understanding in the context of various testicular pathologies will be required.

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PURPOSE: Real-time shear-wave elastography (SWE) is a newly developed technique for the sonographic quantification of tissue elasticity, which already is used in the assessment of breast and thyroid lesions. Due to limited overlying tissue, the testes are ideally suited for assessment using shear wave elastography. To our knowledge, no published data exist on real-time SWE of the testes. MATERIALS AND METHODS: Sixty six male volunteers (mean age 51.86±18.82, range 20-86) with no known testicular pathology underwent normal B-mode sonography and multi-frame shear-wave elastography of both testes using the Aixplorer ® ultrasound system (SuperSonic Imagine, Aix en Provence, France). Three measurements were performed for each testis; one in the upper pole, in the middle portion and in the lower pole respectively. The results were statistically evaluated using multivariate analysis. RESULTS: Mean shear-wave velocity values were similar in the inferior and superior part of the testicle (1.15 m/s) and were significantly lower in the centre (0.90 m/s). These values were age-independent. Testicular stiffness was significantly lower in the upper pole than in the rest of the testis with increasing volume (p = 0.007). CONCLUSION: Real-time shear-wave elastography proved to be feasible in the assessment of testicular stiffness. It is important to consider the measurement region as standard values differ between the centre and the testicular periphery. Further studies with more subjects may be required to define the normal range of values for each age group. Useful clinical applications could include the diagnostic work-up of patients with scrotal masses or male infertility.

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PURPOSE: The aim of this study was to evaluate the clinical and functional outcomes in patients who underwent selective interventional embolization of renal pseudoaneurysms or arteriovenous fistulas at our center. MATERIALS AND METHODS: Our retrospective analysis included all consecutive patients who received selective transcatheter embolization of renal pseudoaneurysms or arteriovenous fistulas after partial nephrectomy in our department from January, 2003 to September, 2013. The technical and clinical success rate and functional outcome of every procedure was collected and analyzed. Furthermore, the change in renal parenchymal volume before and after embolization was determined in a subgroup. RESULTS: A total of 1425 patients underwent partial nephrectomy at our hospital. Of these, 39 (2.7 %) were identified with a pseudoaneurysm or an arteriovenous fistula after partial nephrectomy. The diagnosis of the vascular lesions was made by means of biphasic CT or CEUS. Technical success by means of selective microcoil embolization was achieved in all 39 patients (100 %). Clinical success, defined as no need for further operation or nephrectomy during follow-up, was achieved in 35 of 39 patients (85.7 %). Renal function, as measured by eGFR before and after the intervention, did not change significantly. However, a mean loss of parenchymal volume of 25.2 % was observed in a subgroup. No major or minor complications were attributable to the embolization procedure. CONCLUSION: Transcatheter embolization is a promising method for treating vascular complications which may occur after partial nephrectomy. We confirm the high success rate of this technique while discussing renal functional outcomes and potential safety aspects. KEY POINTS: Arterial pseudoaneurysms and arteriovenous fistulas are rare but severe complications after partial nephrectomy. Selective microcoil embolization is a safe and effective kidney-preserving procedure for treating these complications. Embolization leads to a significant loss of renal parenchymal volume but not to a loss of renal function.

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Cross-sectional imaging modalities including multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) are the diagnostic standard in detection, characterization, and staging of renal masses due to their high sensitivity and specificity. Currently, most renal masses are incidentally diagnosed by imaging for other medical reasons. Recent developments have improved image acquisition with high resolution, while simultaneously reducing radiation dose. CT imaging is the most accessible cross-sectional imaging method and is, therefore, the standard technique. MRI is indicated in patients who are allergic to intravenous CT contrast medium, in patients with renal insufficiency, or in younger patients. Further characterization of renal masses is possible with functional imaging including dual energy CT, perfusion CT, or diffusion-weighted MRI. Contrast-enhanced ultrasound allows detection of even subtle enhancement in hypovascular lesions with high sensitivity and can add valuable information to CT and MRI studies.

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PURPOSE: To compare the value of high-resolution contrast-enhanced ultrasound in the detection and characterisation of endoleaks after EVAR. MATERIAL AND METHODS: In this retrospective study, a cohort of 80 patients underwent both standard examination using a curved array 5 MHz transducer and a second examination using a curved array 9 MHz transducer. The examination included B-mode, color Doppler and contrast-enhanced ultrasound using the Philips EPIQ 7 scanner. RESULTS: 80 patients were included in the study. CEUS was used as the preferred examination in determining the presence of an endoleak. The sensitivity and specificity for the detection of endoleak using the 5 MHz transducer was: CEUS (96.8%, 100%), Color Doppler (47.6%, 94.1%), B-mode (15.8%, 94.1%), while for the 9 MHz transducer: CEUS (100%, 100%), Color Doppler (39.7%, 94.1%), B-mode (23.8%, 24.1%). CONCLUSION: High resolution ultrasound (9 MHz) in detection and characterization of endoleaks after EVAR has some minor advantages in comparison to lower resolution ultrasound (5 MHz).

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PURPOSE: Virtual touch tissue imaging quantification (VTIQ) is a newly developed technique for the sonographic quantification of tissue elasticity. It has been used in the assessment of breast lesions. The purpose of this study was to determine the diagnostic performance of VTIQ in indeterminate testicular lesions. METHODS: Twenty patients with known testicular pathology underwent conventional B-mode sonography with additional VTIQ of the testicular lesions using a Siemens Acuson S2000™ and S3000™ (Siemens Medical Solutions, Mountain View, CA, USA) system. Tissue mechanical properties were analysed in the VTIQ examination. The pathologic diagnosis was established after surgery or in the follow-up examination for suspected benign lesions. RESULTS: Over 36 months, 22 focal testicular lesions (median lesion size, 18 mm; range, 4-36 mm in 20 patients (median age, 43 years; range, 22-81 years) were examined. Lesions were hyperechoic (n = 1), hypoechoic (n = 14), isoechoic (n = 1), of mixed echogenicity (n = 3) or anechoic (n = 3). Histological examination showed one benign lesion (6.25%) with a mean size of 7 mm and 15 malignant lesions (93.75%) with a mean size of 20 mm. Mean shear wave velocity for normal testicular tissue was 1.17 m/s. No shear wave velocity could be measured in cystic lesions. The rest of the benign lesions showed a mean shear wave velocity of 2.37 m/s. The value of the shear wave velocity in germ cell tumours showed a mean shear wave velocity of 1.94 m/s and for seminoma it showed a mean shear wave velocity of 2.42 m/s. CONCLUSIONS: VTIQ is a reliable new method for measuring qualitative and quantitative stiffness of testicular lesions and tissue. The qualitative shear-wave elastography features were highly reproducible and showed good diagnostic performance in unclear testicular lesions. The VTIQ technique is also useful in assessing small testicular nodules and pseudolesions.

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OBJECTIVES: Multicentre evaluation of the precision of semi-automatic 2D/3D measurements in comparison to manual, linear measurements of lymph nodes regarding their inter-observer variability in multi-slice CT (MSCT) of patients with lymphoma. METHODS: MSCT data of 63 patients were interpreted before and after chemotherapy by one/two radiologists in five university hospitals. In 307 lymph nodes, short (SAD)/long (LAD) axis diameter and WHO area were determined manually and semi-automatically. Volume was solely calculated semi-automatically. To determine the precision of the individual parameters, a mean was calculated for every lymph node/parameter. Deviation of the measured parameters from this mean was evaluated separately. Statistical analysis entailed intraclass correlation coefficients (ICC) and Kruskal-Wallis tests. RESULTS: Median relative deviations of semi-automatic parameters were smaller than deviations of manually assessed parameters, e.g. semi-automatic SAD 5.3 vs. manual 6.5 %. Median variations among different study sites were smaller if the measurement was conducted semi-automatically, e. g. manual LAD 5.7/4.2 % vs. semi-automatic 3.4/3.4 %. Semi-automatic volumetry was superior to the other parameters (2.8 %). CONCLUSIONS: Semi-automatic determination of different lymph node parameters is (compared to manually assessed parameters) associated with a slightly greater precision and a marginally lower inter-observer variability. These results are with regard to the increasing mobility of patients among different medical centres and in relation to the quality management of multicentre trials of importance. KEY POINTS: • In a multicentre setting, semi-automatic measurements are more accurate than manual assessments. • Lymph node volumetry outperforms all other semi-automatically and manually performed measurements. • Use of semi-automatic lymph node analyses can reduce the inter-observer variability.

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CLINICAL/METHODICAL ISSUE: Robust and reliable imaging methods are required to estimate the skeletal tumor load in multiple myeloma, as well as for the diagnosis of extraskeletal manifestations. Imaging also plays an essential role in the assessment of fracture risk and of vertebral fractures. STANDARD RADIOLOGICAL METHODS: The conventional skeletal survey has been the gold standard in the imaging of multiple myeloma for many years. METHODICAL INNOVATIONS: Other modalities which have been investigated and are in use are whole-body computed tomography (WBCT), 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET-CT) and whole-body magnetic resonance imaging (WBMRI). These techniques are able to depict both mineralized bone and the bone marrow with a high sensitivity for myeloma lesions. PERFORMANCE: Several studies have shown that cross-sectional imaging is superior to the skeletal survey in the detection of myeloma lesions and WBMRI has been shown to be significantly more sensitive than WBCT for the detection of focal myeloma lesions as well as for diffuse infiltration. The FDG PET-CT technique has a sensitivity comparable to WBMRI. ACHIEVEMENTS: Due to the higher sensitivity in the detection of myeloma lesions WBCT and WBMRI should replace the skeletal survey. PRACTICAL RECOMMENDATIONS: A WBCT should be performed if there is suspicion of multiple myeloma. If no focal lesions are found WBMRI or at least MRI of the spine and pelvis should be additionally performed if available. If WBMRI has been initially performed and focal lesions are present, an additional WBCT may be performed to assess the extent of bone destruction and fracture risk. In cases of monoclonal gammopathy of undetermined significance (MGUS), solitary and smoldering myeloma, a WBMRI, if available, should be performed in addition to WBCT.

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PURPOSE: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. MATERIALS AND METHODS: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. RESULTS: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. CONCLUSION: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. KEY POINTS: ► Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients ► Manual lymph node evaluation with uni-dimensional parameters is inferior to semi-automatic analysis in a multicenter setting ► Semi-automatic quantitative software tools should be introduced in clinical study evaluation.

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Oncologic imaging and reporting are an important part of clinical trials and have to be performed according to standardized criteria that clearly define how certain changes in the size and number of tumorous lesions have to be rated. Knowledge of these criteria is not only crucial when interpreting cases for a clinical trial but may also be used as guidelines for everyday clinical reporting as they aid decision making and can increase the validity of radiologic reporting.This article summarizes the most important and frequently used criteria: the response evaluation criteria in solid tumors (RECIST) criteria which are only used in solid malignancies, the Choi criteria that have been designed for the assessment of gastrointestinal stroma tumors (GIST), and the Cheson criteria that are applied to malignant lymphomas. The compilation of these criteria is designed to be used as a repetitorium for experts and can also serve as training guidelines for junior radiologists who want to become involved in clinical trial reporting.

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PURPOSE: To evaluate the feasibility of the classification of endoleaks following endovascular aortic aneurysm repair using the time-to-peak of the contrast agent in CEUS examinations. MATERIAL AND METHODS: In this retrospective study, a cohort of 171 patients with a total of 489 CEUS follow-up examinations after EVAR were included. In 254 of the 489 examinations, an endoleak was seen and the time-to-peak was measured in seconds. Existence of an endoleak was confirmed by CT as the gold standard. RESULTS: We evaluated 254 CEUS video sequences showing an endoleak out of a total of 489 examinations. Kruskal-Wallis test revealed with p = 0.001 differences between the single endoleak types based on the time to peak. Correction after Bonferroni showed significant differences between type Ia compared to Ib and to IIa over inferior mesenteric artery (IMA) and IIa over lumbar artery (LA). There are also disparities between type Ib and type IIa IMA and type III, furthermore between type IIa IMA compared to IIa LA and type III as well as type IIa LA matched to type III. CONCLUSION: CEUS is an important method for the follow-up after EVAR. The time-to-peak does not seem to be a useful additional feature in classifying endoleaks, although there are differences between the time-to-peak of the single endoleak types and it is possible to make an order of the different endoleak types referring to the mean values.

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Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy with a prevalence of 1 out of 2,500 in adults. Due to mild clinical symptoms in the early phase of the disease, the true prevalence is probably even much higher. Patients present with variable clinical symptoms ranging from mild systolic impairment of left ventricular function to congestive heart failure. Even sudden cardiac death may be the first clinical symptom of DCM. The severity of the disease is defined by the degree of impairment of global left ventricular function. Arrhythmias, such as ventricular or supraventricular tachycardia, atrioventricular (AV) block, ventricular extrasystole and atrial fibrillation are common cardiac manifestations of DCM. Magnetic resonance imaging (MRI) plays an important role in the exact quantification of functional impairment of both ventricles and in the evaluation of regional wall motion abnormalities. With its excellent ability for the assessment of myocardial structure, it is becoming increasingly more important for risk stratification and therapy guidance.

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Ultrasound is often the first imaging modality used in the diagnosis of abdominal vascular as well as parenchymal organ pathologies. Contrast-enhanced ultrasound (CEUS) enables the dynamic assessment and quantification of microvascularisation up to capillary perfusion. Current clinical applications of CEUS are mainly in detection and characterization of lesions, particularly benign and malignant hepatic and renal lesions, based on differences between lesion and organ perfusion. Multifrequency high-resolution transducers are being increasingly used, including intra-operatively. Dynamic 3D techniques and ultrasound image fusion with CT or MRI may assist the diagnosis and therapy control after interventional procedures. Our own studies have demonstrated the excellent diagnostic performance of CEUS with perfusion-analysis in the characterization of hepatic and renal lesions as well as the assessment of tissue transplant macro- and microvascularisation. CEUS opens up new possibilities in the characterization of the microvasculature with perfusion analysis, even during the course of interventions, thereby providing new possibilities for modified therapeutic strategies. In this review, the different new ultrasound techniques with their potential applications are described and illustrated.

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