First assessment of flow phenomena of acute and chronic thrombosis in the jugular veins using new ultrasound vector-flow imaging.

AIM: First assessment of flow changes in the jugular veins using high resolution ultrasound vector flow. MATERIAL UND METHODS: 15 patients (8 males, 7 females) with an age range of 35 to 82 years (mean age 58.53±12.26 years) were examined by an experienced examiner using high power ultrasound equipment (Resona R9, Mindray) with probe technology (Mindray L9-3U Linear Array transducer, 2.5 to 9.0 MHz). This group was compared with five healthy subjects (mean age 35.4±13.79 years) as a reference. To assess flow changes, the color-coded duplex sonography and the novel vector flow technique were used. The evaluation was performed of vector morphology changes, turbulence, and wall resistance measurements. RESULTS: There were changes after acute and chronic thrombosis in 9 cases, and venous compression in 7 cases. Turbulence was measurable from 0.01 % to 64.44 %, the average turbulence was 19.73±22.06 %. Wall resistance measurement showed values from 0.01 Pa to 3.14 Pa, depending on the age of the thrombosis or compression. The reference veins showed turbulence of 0.94±1.5 % and a mean wall resistance of 0.05±0.05 Pa. There are statistically significant differences between normal and thrombotic or compressed veins in terms of maximum wall stress (p = 0.006) and mean degree of turbulence (p = 0.012), while the difference in mean wall stress is not statistically significant (p = 0.058). CONCLUSION: Despite still existing technical limitations, the combination of V-flow and wall stress measurements in jugular vein changes suggests a high diagnostic potential.

The value of sonographic microvascular imaging in the diagnosis of lipedema.

BACKGROUND: Lipedema is a chronic disease marked by symmetric enlargement of painful nodular and fibrotic adipose tissue, predominantly affecting the limbs. Since there is no specific test or biomarker for this condition, years often pass before the diagnosis of lipedema is established for the first time, thereby causing psychosocial distress, including depression, eating disorders, and social isolation. Over the last few years several advanced Doppler-based technologies have been developed to visualize slow flow blood vessels and superficial microvascular architecture undetectable by traditional color Doppler flow imaging (CDFI). OBJECTIVE: The aim of this study was to evaluate the superficial microvascular anatomy in lipedema patients compared to healthy controls and investigate the clinical significance of the Ultra Micro Angiography (UMA) technology in the diagnosis of lipedema. This new technique may contribute to reduce the diagnostic delay and, eventually, establish and guide treatment strategies toward a better therapeutic outcome in lipedema patients. METHODS: 25 patients with lipedema and ten healthy controls with no history of lipedema were included in this study. All ultrasound examinations were performed on a novel high-performance ultrasound system (Resona R9/Mindray) using CDFI and the UMA technique. RESULTS: In all of the patients, Ultra Micro Angiography achieved the excellent visualization of microvascular structures, revealing that most lipedema patients showed grade 3 (n = 13) or grade 2 (n = 8) flow. UMA was superior to CDFI for depicting the microvascular structures. CONCLUSIONS: Here we show that UMA imaging characterizes the subcutaneous microvasculature with an unprecedented accuracy. The method has the advantage of being sensitive to small, slow-flowing vessels. This allows for the assessment of the course of vessels and vascular pathologies in great detail. Thus, UMA as a non-invasive diagnostic method can improve diagnostic accuracy in lipedema.

Initial phase establishment of an in vitro method for developmental neurotoxicity test using Ki-67 in human neural progenitor cells.

Building a precise alternative neurotoxicological test is of great importance to respond to societal and ethical requirements. In this study, a new developmental neurotoxicity test (DNT) was established with the human neural progenitor cell line. ReNcell CX cells were exposed to neurotoxic chemicals (aphidicolin, hydroxyurea, cytosine arabinoside, 5-fluorouracil, and ochratoxin A) or non-neurotoxic chemicals (sodium gluconate, sodium bicarbonate, penicillin G, and saccharin). Propidium iodide (PI) was used to evaluate cell viability. BrdU and Ki-76 were employed to determine cell proliferation. Based on the cell viability and proliferation, mathematical models were built by linear discriminant analysis. Furthermore, the neurotoxic-considered chemicals inhibited cell cycle progression at the protein level, supporting the biomolecular rationale for the predictive model. Overall, these results show that the new test method can be used to determine the potential developmental neurotoxicants or new drug candidates.

Advanced multimodal imaging of solid thyroid lesions with artificial intelligence-optimized B-mode, elastography, and contrast-enhanced ultrasonography parametric and with perfusion imaging: Initial results.

 Goal of the study was the assessment of AI-assisted diagnosis of solid thyroid foci with multimodal modern ultrasound imaging. 50 patients (26-81 years, 54.7±13.1 years) were included in the study. Multimodal ultrasound imaging by means of B-mode with linear probe (4-12 MHz) with option of automated documentation of findings by means of AI, with supplementary Ultra MicroAngiography (UMA) was used. Macrovascularisation was assessed by dynamic contrast ultrasonography (CEUS) with parametric evaluation and perfusion analysis, and microvascularization was assessed by combined strain and shear wave elastography on a novel high-performance ultrasound system (Resona R9/Mindray) by an experienced examiner with independent reading. The evaluation was performed according to TI-RADS III-V.The volume of the thyroid lobes on both sides averaged 39 ml±5 ml (27 to 69 ml). The 13 cases of histologically confirmed thyroid carcinomas (8 papillary, 2 medullary, 2 microfollicular, 1 anaplastic CA) with a mean size of 15 mm±6 mm (9-21 mm) were correctly evaluated by TI-RADS V on the basis of irregular shape, induration > 2.5 m/s or > 30kPA and striking wash-out kinetics. Tumor lymph nodes could only be correctly detected preoperatively in one case of medullary carcinoma according to the surgical findings, based on irregular vascularization with UMA in roundish shape with cortex > 4 mm, transverse diameter up to 11 mm. In 25 cases of inhomogeneous nodular goiter an evaluation with TI-RADS III was performed in 31 cases, in 4 cases with incomplete marginal contour, partial marginal vascularization with UMA and partial wash out with indurations up to 2.5 m/s 30 kPA an evaluation with TI-RADS IV and surgical excision for nodular goiter. In 12 cases regressive nodular changes without relevant malignancy criteria resulted in nodular goiter, with focal changes up to 1.5 cm in diameter, classified as requiring control with TI-RADS III. There were no relevant changes in findings in the controls after 6 months. From the AI tool, the 20/25 goiter nodes were assessed as TI-RADS III, 7/12 adenomas, 5 goiter nodes, and 5 adenomas as TI-RADS IV, 5/13 carcinomas as TI-RADS IV, and 8/13 carcinomas as TI-RADS V.Multimodal ultrasound diagnostics supported by AI has a high diagnostic potential for the evaluation of solid thyroid lesions and standardizes the reporting with digital representative image documentation. CEUS perfusion and modern elastography techniques allow targeted follow-up of TI-RADS III findings.

Current aspects of multimodal ultrasound liver diagnostics using contrast-enhanced ultrasonography (CEUS), fat evaluation, fibrosis assessment, and perfusion analysis - An update.

Current ultrasound multifrequency probes allow both improved detail resolution and depth of penetration when examining the liver. Also, new developments in vascular diagnostics, elastography with fibrosis assessment, evaluation of possible steatosis, and parametric and time intensity curve (TIC) analysis of dynamic microvascularization of the liver with contrast-enhanced ultrasound sonography (CEUS) complement ultrasound-guided diagnostics. State-of-the-art high-resolution technology includes a high frame rate (HiFR) mode for CEUS, fast shear wave measurements with the sound touch quantify (STQ) mode, artifact-free flow detection using HR flow and glazing flow in combination with a special flow-adapted imaging (Ultra Micro Angiography, UMA) and additionally different assessments of possible fatty liver (UltraSound ATtenuation Imaging Technology, USAT). In 50 cases with focal liver lesions, a multimodal liver diagnosis was performed with a still new high-performance ultrasound system as part of the clarification of questions from the university liver consultation and tumor outpatient clinic.

Post-mortem distribution of Iodinated Contrast Media (ICM) (iodixanol versus iopromide) in the porcine kidney after multiple bolus injections in vivo into the supra-renal aorta1.

 Iodinated contrast media (ICM) are widely used for diagnostic and interventional procedures in radiology and cardiology. Ideally, they should not interact with blood cells or vascular wall cells to avoid deteriorations of the blood circulation. However, it is well known that ICM can affect erythrocytes as well as endothelial cells which consequently might perturb especially the microcirculation. In former studies the influence of two ICM (iodixanol versus iopromide) on the vascular system, the development of blood stasis, on changes in renal resistive index (RRI) and vascular diameters, and on the post-mortem distribution of iodine as marker for ICM in the explanted kidneys was examined. The modus of ICM application into the supra-renal aorta followed the regime in interventional cardiology, so that 10 bolus injections were administered at steady intervals (iopromide 4,32 ml / iodixanol 5 ml) accompanied by infusion of 500 ml isotonic NaCl-solution.In the present study, the post-mortem X-ray analysis revealed that there were no differences in iodine content in the regions of the mid-cortex and the medullo-pelvic transition zone of the kidneys after application of both ICM. Remarkable differences, however, were found in the region of the capsule-near cortex, where the application of iopromide led to a significantly lower iodine content in the microcirculation. This is in good agreement with former studies, in which a maldistribution in this area, presumably due to a decrease in arteriolar inflow as a result of stasis/occlusion was shown.

Multimodal ultrasound imaging with conventional B-mode, elastography, and parametric analysis of contrast-enhanced ultrasound (CEUS): A novel approach to assess small bowel manifestation in severe COVID-19 disease.

The aim was to describe the small bowel morphology with conventional B-mode and elastography and additionally to evaluate dynamic effects of COVID-19 associated small bowel microvascularization using CEUS with color coded perfusion parameters.Thirteen patients with severe COVID-19 acute respiratory distress syndrome (ARDS) were investigated. 13 patients required intensive care treatment with mechanical ventilation. Five patients required extracorporeal membrane oxygenation (ECMO). Contrast-enhanced ultrasound (CEUS) was performed by an experienced investigator as a bolus injection of up to 2.4 ml sulfur hexafluoride microbubbles via a central venous catheter. In the parametric analysis of CEUS, the flare of microbubbles over time is visualized with colors. This is the first work using parametric analysis of CEUS to detect perfusion differences in the small bowel.Parametric analysis of CEUS in the intestinal phase was carried out, using DICOM loops for 20 seconds. In 5 patients, parametric analysis revealed intraindividual differences in contrast agent behavior in the small bowel region. Analogous to the computed tomography (CT) images parametric analysis showed regions of simultaneous hyper- and hypoperfusion of the small intestine in a subgroup of patients. In 5 patients, the parametric image of transmural global contrast enhancement was visualized.Our results using CEUS to investigate small bowel affection in COVID-19 suggest that in severe COVID-19 ARDS systemic inflammation and concomitant micro embolisms may lead to disruption of the epithelial barrier of the small intestine.This is the first study using parametric analysis of CEUS to evaluate the extent of small bowel involvement in severe COVID-19 disease and to detect microemboli. In summary, we show that in COVID-19 the small bowel may also be an important interaction site. This is in line with the fact that enterocytes have been shown to a plenitude of angiotensin converting enzyme (ACE)-2 receptors as entry sites of the virus.

Contrast enhanced ultrasonography (CEUS) a novel tool to detect intestinal epithelial barrier dysfunction in severe COVID-19 disease.

Ten patients with confirmed COVID-19 disease were studied. Nine patients required intensive care treatment, among them four needed extracorporeal membrane oxygenation (ECMO). Contrast enhanced ultrasonography (CEUS) was performed by one experienced investigator as a bolus injection of up to 2.4 ml of sulphur hexafluoride microbubbles via a central venous catheter. B-Mode evaluation and strain elastography showed mural edema of the small bowel with a thickness of up to 10 mm in all patients. We applied color coded Doppler sonography (CCDS) and power mode with flow-adapted parameters and early, dynamic capillary arterial contrast enhancement of bowel wall structures <10 s to assess perfusion of the small bowel. In all patients, reactive hyperemia was seen in the entire small bowel. In a subgroup of seven patients microbubbles translocated into the intestinal lumen. Thus, high-grade intestinal barrier disruption secondary to SARSCoV-2 infection can be postulated in these patients.This is the first description of perfusion changes and a disruption of the small bowel epithelial barrier in COVID-19 Patients using contrast ultrasonography and elastography.

Dynamic endoluminal contrast enhanced ultrasound (CEUS) for display of drainages in inflammatory abdominal fluid collections1.

AIM: To evaluate the additive clinical value of endoluminal contrast enhanced ultrasound (CEUS) after interventional placement of drainages in abdominal fluid collections. MATERIAL/METHOD: Examination of 30 patients using a 1-6 MHz convex probe (Resona 7, Mindray) to locate the fluid collection in B-Mode. Additionally, dynamic endoluminal CEUS with 1 ml sulphur-hexafluoride microbubbles was performed to measure the extent of the percutaneously drained abscesses. Independent assessment of dynamically stored images in PACS in DICOM format. Correlation to reference imaging using computed tomography (CT). RESULTS: A total of 30 patients were examined (17 m, 19-78 years, mean 56.1 years). Drainages were positioned in the liver in 15 cases, in the pelvis after kidney transplantation in 4 cases, close to the spleen in 1 case, and in the abdomen in 10 cases. In all cases abscesses showed marginal hyperaemia with reactive septations in CEUS. The drainage position was assessed by means of B-mode in all cases first and then by CEUS. In 4 cases CEUS showed a fistula to the pleura, in 5 cases to the peritoneum, in 2 cases to the intestine, in 5 cases to the biliary tract, corresponding to the CT. In 2 cases there was a hint of an anastomotic leakage after intestinal anastomosis, which was reliably detected by CT. The drainage was removed in 11 cases within a period of 2 to 5 days after CEUS control, in 9 cases within a period of 5 to 10 days. Another operation was necessary in 3 cases. A new drainage was placed in 2 cases. The required amount of ultrasound contrast medium is 1 ml endoluminally diluted to 9 ml sodium chloride. CONCLUSION: CEUS facilitates the exact localization and characterization of inflammatory abdominal fluid collections. Furthermore, possible fistulas can be detected that cannot be seen with conventional ultrasound.

Surface imaging of breast implants using modern high-frequency ultrasound technology in comparison to high-end sonography with power analyses for B-scan optimization1.

AIM: This study aims to evaluate optimized breast implant surface-structure analysis by comparing high-end ultrasound technology with a new high frequency technique. This comparative study used new breast implants with different surfaces in an in vitro setting. METHODS: Nine idle silicon or polyurethane (PU) breast implants were examined by two investigators in an experimental in vitro study using two high-end ultrasound devices with multi-frequency transducers (6-15 MHz, 9-16 MHz, 12.5-33 MHz).The ultrasound B-Mode was optimized using tissue harmonic imaging (THI), speckle reduction imaging (SRI, level 0-5), cross beam (high, medium, low) and photopic.Using a standardized ultrasound protocol, the implants were examined in the middle (point of highest projection) and lateral, by two independent examiners.Image evaluation was performed on anonymized digital images in the PACS. The aim was to achieve an artifact-free recording of the surface structure, the surface coating, the total image structures and, as far as possible, an artifact-free internal representation of the implants.For independent surface evaluation a score was used (0 = undetectability of surface structures, rich in artifacts, 5 = best possible, artifact free image quality). RESULTS: The quality of ultrasound imaging of breast implant surfaces after the optimization of B-Scan differed significantly comparing high-end ultrasound technology with modern high-frequency ultrasound technology (p < 0,05).The following setting has been found to be the best setting with the highest image quality:B-Mode, SRI value 3, Crossbeam high level with color coded imaging for B- mode. In the total examined frequency range of 6-33 MHz, the highest image quality was found in the average frequency range of 12.5-33 MHz at both measured points. For both devices, device 1 (high-end) and device 2 (high frequency) ultrasound, the image quality was in the12.5-33 MHz frequency range with an average image quality of 3.236. It was significantly higher, than in the lower frequency ranges and the same frequency range with THI. (p < 0,05). The image quality of the high-end sonography device was superior to the conventional high-frequency ultrasound device in all frequency ranges. CONCLUSION: High-end ultrasound imaging technology was superior in the quality of implant surface evaluation in comparison to high-frequency ultrasound sonography. The gained knowledge can serve as a basis for further multicenter clinical application and studies with the aim to develop an objective, precise tool to evaluate the implant and the surrounding tissue with ultrasound.

High-performance sonographical multimodal imaging of non cystic thyroid lesions: Chances of the preoperative diagnostics in relation to histopathology.

AIM: To improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance ultrasound techniques: optimized B-mode morphology, elastography, Color-Coded Doppler-Sonography (CCDS) and contrast enhanced ultrasound (CEUS)MATERIALS AND METHODS:In 33 cases solid, non-cystic thyroid lesions were rated as TIRADS 3 and up from conventional B-mode examinations. Additional high resolution Power Doppler including HR- and Glazing-Flow as optimized macrovascularization techniques, shear wave elastography and CEUS were performed on these patients by one experienced examiner. For CEUS a bolus of 1-2.4 ml Sulfurhexafluorid microbubbles (SonoVue®, Bracco, Milan, Italy) was injected into a cubital vein and then the distribution kinetics of the contrast agent were documented from the early arterial phase (10 to 15 seconds after injection) to the late venous phase (5 minutes after injection). Postoperative histopathology was the diagnostic gold standard as it provides the most reliable proof. RESULTS: 33 patients (13 males, 20 females; age 29 -77 years; mean 55 years; SD 13 years) were included in this study. 28 of them had benign regressive thyroid nodules, 3 had adenomas and 4 were diagnosed with carcinomas (3 were histologically identified as papillary thyroid carcinomas, one as a medullary thyroid carcinoma). The volume of the thyroid gland ranged from 6.6 to 401.3 cm2 (mean 72.6±92.0 cm2).The adenoma diameters ranged from 9 to 40 mm (mean 22±16 mm) and the carcinoma diameters ranged from 19 to 33 mm (mean 26±6 mm). The 3 adenomas had different echogenicities: One was completely echofree, one was hypoechoic and one isoechoic. The 4 carcinomas however were equally characterized as hypoechoic and echofree. Two of three adenomas and all of the carcinomas showed an incomplete or diffuse margin. Micro-calcifications were found in one adenoma and in every carcinoma. However, no micro-calcifications were observed in cases of benign regressive nodules.Performing shear-wave elastography the adenomas showed lower values than the carcinomas: The tissue velocity of the adenomas ranged from 2.86 m/s to 3.85 m/s (mean 3.32±0.5 m/s) and in carcinomas from 3.89 m/s to 5.66 m/s (mean 4.18±0.3 m/s).Marginal hypervascularization was detected in two adenomas after applying CCDS. One adenoma was hypovascularized. The four carcinomas showed an irregular extreme hypervascularization along their margins as well as an irregular central normo- or hypervascularization in CCDS. The additional HR-Flow helped reducing artefacts.In CEUS the dynamic capillary microvascularization of all carcinomas was very irregular with early enhancement and followed by partial or complete wash-out. In CEUS two adenomas had no wash-out and the other one showed a partial wash-out. CONCLUSION: Using modern multimodal imaging offers new possibilities for the differentiation between benign and malignant thyroid lesions. It is a very important diagnostic tool in addition to the B-Mode TIRADS classification and eases the decision between TIRADS 3, 4 and 5. However, additional multicenter studies are required for more detailed evaluations.

High resolution flow (HR Flow) and Glazing Flow in cases of hepatic flow changes: Comparison to color-coded Doppler sonography (CCDS).

AIM: To evaluate the possibilities of flow detection using high resolution flow (HR Flow) and Glazing Flow technique in patients with liver parenchymal changes and flow changes in comparison to color-coded Doppler sonography (CCDS). MATERIAL AND METHODS: All examinations were performed using a multi frequency matrix convex probe with high resolution technique (SC6-1U/Resona7, Mindray, Shenzhen, China) by one experienced examiner to evaluate the venous, portal venous and arterial liver flow with digital documentation of the dynamic flow parameters like peak systolic flow, end-diastolic flow and resistance index. For liver parenchymal stiffness changes shear wave elastography was performed with at least 10 measurements. By two independent readers an elevation was performed to evaluate the image quality and the degree of flow artefacts, from 0 = not available to 5 points with excellent image quality without flow artefacts. RESULTS: All 40 patients (24 men, 16 women, age 27-83 years, mean 56±5 years) showed morphology changes from B-Mode of the liver parenchyma to inhomogeneous tissue with higher stiffness evaluated by the shear wave elastography (1.45 m/s up to 2.79 m/s±1.79 m/s, considering F1 up to F4 fibrosis) and in 15 cases histopathologically proven liver cirrhosis. In 9 cases after non-acute thrombosis flow reduction of the portal vein was the reason for the diameter less than 5 mm. Flow parameters for the venous flow were between 8 cm/s up to 29 cm/s, mean 14±4 cm/s, for the hepatic portal vein 5 cm/s up to 57 cm/s, mean 17±5 cm/s, for the hepatic artery systolic flow between 50 cm/s up to 127±33 cm/s, end-diastolic flow from 22 cm/s up to 47±8 cm/s. Resistance index for the hepatic artery was between 0.41 up to 0.73, mean 0.67±0.25. The image quality for CCDS over all cases was evaluated for CCDS between 1 up to 4. The mean quality was 2.5±0.5, for HR Flow in combination with Glazing Flow 3±0.5, with significant differences for the 2 readers (P < 0.01). CONCLUSION: Combination of HR Flow with Glazing Flow could be helpful to evaluate morphological und hemodynamic changes of liver arterial flow, portal venous and venous flow. Reduction of flow artefacts in combination with a higher image quality could be helpful for optimizing the digital measurements also for follow up examinations.

Wireless point-of-care ultrasound: First experiences with a new generation handheld device.

AIM: To evaluate the diagnostic reliability of a new generation wireless point-of care ultrasound device for abdominal and thoracic findings. MATERIAL AND METHODS: 40 patients (16 females, 24 males 19 -80 years, on average 56.1 years) were scanned by an experienced examiner using the new wireless Vscan Air device for abdominal and thoracic findings. The probe frequencies were 2-5 MHz (convex probe) and 3-12 MHz for the linear probe. As a reference standard, all patients were also examined using high-end ultrasound (LOGIQ E9/LOGIQ E10). Results were interpreted independently by two examiners in consensus, also with regard to the image quality (0-4, from not assessable = 0, to excellent 4). RESULTS: In all 40 patients (100%) examination with conventional high-end ultrasound and the Vscan Air ultrasound device was feasible. Sensitivity, specificity, positive and negative predictive value for the diagnosis of abdominal and thoracic findings were 63.3%, 100%, 100%, and 40%, respectively. Most main diagnostic findings were detected using the mobile device compared to the high-end ultrasound. Limitations were found regarding characterization and classification of hepatic and renal tumorous lesions.Image quality revealed mostly minor diagnostic limitations for the mobile device, mean 2.9 (SD ± 0.300) and was excellent or with only minor diagnostic limitations for conventional high-end ultrasound, mean 3.25 (SD ± 0.438). CONCLUSION: Due to its easy application and its high diagnostic reliability, point-of-care ultrasound systems of the latest generation represent a valuable imaging method for the primary assessment of abdominal and thoracic findings, especially in patients on intensive care units or in emergency situations.

Real-life assessment of standardized contrast-enhanced ultrasound (CEUS) and CEUS algorithms (CEUS LI-RADS®/ESCULAP) in hepatic nodules in cirrhotic patients-a prospective multicenter study.

OBJECTIVES: Hepatocellular carcinoma (HCC) can be diagnosed non-invasively with contrast-enhanced ultrasound (CEUS) in cirrhosis if the characteristic pattern of arterial phase hyperenhancement followed by hypoenhancement is present. Recent studies suggest that diagnosis based on this "hyper-hypo" pattern needs further refinement. This study compares the diagnostic accuracies of standardized CEUS for HCC according to the current guideline definition and following the newly developed CEUS algorithms (CEUS LI-RADS®, ESCULAP) in a prospective multicenter real-life setting. METHODS: Cirrhotic patients with liver lesions on B-mode ultrasound were recruited prospectively from 04/2018 to 04/2019, and clinical and imaging data were collected. The CEUS standard included an additional examination point after 4-6 min in case of no washout after 3 min. The diagnostic accuracies of CEUS following the guidelines ("hyper-hypo" pattern), based on the examiner's subjective interpretation ("CEUS subjective"), and based on the CEUS algorithms ESCULAP and CEUS LI-RADS® were compared. RESULTS: In total, 470 cirrhotic patients were recruited in 43 centers. The final diagnosis was HCC in 378 cases (80.4%) according to the reference standard (histology 77.4%, MRI 16.4%, CT 6.2%). The "hyper-hypo" pattern yielded 74.3% sensitivity and 63% specificity. "CEUS subjective" showed a higher diagnostic accuracy (sensitivity, 91.5%; specificity, 67.4%; positive predictive value, 92%; negative predictive value, 66%). Sensitivity was higher for ESCULAP (95%) and "CEUS subjective" (91.5%) versus CEUS LI-RADS® (65.2%; p < 0.001). Specificity was highest for CEUS LI-RADS® (78.6%; p < 0.001). CONCLUSIONS: CEUS has an excellent diagnostic accuracy for the non-invasive diagnosis of HCC in cirrhosis. CEUS algorithms may be a helpful refinement of the "hyper-hypo" pattern defined by current HCC guidelines. KEY POINTS: • Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy for the non-invasive diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. • The CEUS algorithm ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) showed the highest sensitivity, whereas the CEUS LI-RADS® (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System) algorithm yielded the highest specificity. • A standardized CEUS examination procedure with an additional examination point in the late phase, after 4-6 min in lesions with no washout after 3 min, is vital.

Interstitial lung opacities in patients with severe COVID-19 pneumonia by bedside high-resolution ultrasound in association to CO2 retention.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can cause acute respiratory distress syndrome (ARDS). OBJECTIVE: This single centre cross-section study aimed to grade the severity of pneumonia by bed-side lung ultrasound (LUS). METHODS: A scoring system discriminates 5 levels of lung opacities: A-lines (0 points),≥3 B-line (1 point), coalescent B-lines (2 points), marked pleural disruptions (3 points), consolidations (4 points). LUS (convex 1-5 MHz probe) was performed at 6 defined regions for each hemithorax either in supine or prone position. A lung aeration score (LAS, maximum 4 points) was allocated for each patient by calculating the arithmetic mean of the examined lung areas. Score levels were correlated with ventilation parameters and laboratory markers. RESULTS: LAS of 20 patients with ARDS reached from 2.58 to 3.83 and was highest in the lateral right lobe (Mean 3.67). Ferritin levels (Mean 1885µg/l; r = 0.467; p = 0.051) showed moderate correlation in spearman roh calculation. PaCO2 level (Mean 46.75 mmHg; r = 0.632; p = 0.005) correlated significantly with LAS, while duration of ventilation, Horovitz index, CRP, LDH and IL-6 did not. CONCUSIONS: The proposed LAS describes severity of lung opacities in COVID-19 patients and correlates with CO2 retention in patients with ARDS.

Potassium-dependent sodium/calcium exchanger 3 (Nckx3) depletion leads to abnormal motor function and social behavior in mice.

Transcellular calcium transport is an essential activity in mineralized tissue formation, including that in nervous systems. Dysregulation of Ca2+ homeostasis can induce excitotoxicity and neurodegeneration in the central nervous system. Nckx3, a potassium-dependent Na+/Ca2+ exchanger, is most abundant in the brain and has a critical role in the transport of intracellular calcium across the cell membrane. However, the roles of Nckx3 in neuron development and function remain unreported. Herein, we examined the behaviors of Nckx3-knock-out mice at the age of six weeks. Detailed behavioral analyses showed Nckx3-/- mice exhibited an increase in moving distances in the open field test. Additionally, the rotarod test revealed motor learning defects in Nckx3-/- mice. Both Nckx3+/- and Nckx-/- mice also exhibited deficits in sociability and social novelty preference. Furthermore, Nckx-/- mice displayed increased depression-related behavior. However, there was no significant change in cognition function detected in Nckx-/- mice. This study demonstrates that NCKX3 is involved in behavior and neuronal function.

Contrast enhanced ultrasound (CEUS) with parametric imaging and time intensity curve analysis (TIC) for evaluation of the success of prostate arterial embolization (PAE) in cases of prostate hyperplasia.

AIM: To evaluate the use of dynamic contrast enhanced ultrasound (CEUS) with parametric color-coded imaging and time intensity curve analysis (TIC) for planning and follow-up after prostate arterial embolization (PAE). MATERIAL/METHOD: Before and after selective iliacal embolization by PAE with a follow up of 6 months 18 male patients (43-78 years, mean 63±3.5 years) with histopathological proven benign prostate hyperplasia were examined by one experienced examiner. A multifrequency high resolution probe (1-6 MHz) was used for transabdominal ultrasound and CEUS with bolus injections of 2.4 ml sulphur-hexafluoride microbubbles. Independent evaluation of color-coded parametric imaging before and after PAE by in PACS stored DICOM loops from arterial phase (10-15 s) up to 1min were performed. Criteria for successful treatment were reduction of early arterial enhancement by changes of time to peak (TTP) and area under the curve (AUC) by measurements in 8 regions of interest (ROI) of 5 mm in diameter at the margin and in the center and changes from hyperenhancement in parametric imaging (perfusion evaluation of arterial enhancement over 15 s) from red and yellow to blue and green by partial infarctions. Reference imaging method was the contrast high resolution 3 tesla magnetic resonance tomography (MRI) using 3D vibe sequences before and after PAE and for the follow up after 3 and 6 months. RESULTS: PAE was technically and clinically successful in all 18 patients with less clinical symptoms and reduction of the gland volume. In all cases color-coded CEUS parametric imaging was able to evaluate partial infarction after embolization with changes from red and yellow to green and blue colors in the embolization areas. Relevant changes could be evaluated for TIC-analysis of CEUS with reduced arterial enhancement in the arterial phase and prolonged enhancement of up to 1 min with significant changes (p = 0.0024). The area under the curve (AUC) decreased from 676±255.04 rU (160 rU-1049 rU) before PAE to 370.43±255.19 rU (45 rU-858 rU) after PAE. Time to peak (TTP) did not change significantly (p = 0.6877); TTP before PAE was 25.82±9.04 s (12.3 s-42.5 s) and after PAE 24.43±9.10 s (12-39 s). Prostate volume decreased significantly (p = 0.0045) from 86.93±34.98 ml (30-139 ml) before PAE to 50.57±26.26 ml (19-117 ml) after PAE. There were no major complications and, in most cases (14/18) a volume reduction of the benign prostate hyperplasia occurred. CONCLUSION: Performed by an experienced examiner CEUS with parametric imaging and TIC-analysis is highly useful to further establish prostatic artery embolization (PAE) as a successful minimal invasive treatment of benign prostatic hyperplasia.

Functional ultrasound imaging of the venous valve of the great saphenous vein in the area around the crosse using the novel vector flow technique.

PURPOSE: The aim of our pilot study is to consider if the new flow presentation of the vector flow (V-flow) allows an assessment of the valve morphology of the crosses with respect to an insufficiency. MATERIAL AND METHODS: We performed a total of 50 investigations in which we documented a complete valve closure at the so called "crosse" at the valve of the large saphenous vein, a delayed valve closure or an incomplete valve closure with consecutive insufficiency at the crosse. The valve function of the crosse is crucial for the development of varicosis. For our study we recorded age and gender of the patients. One patient in the study was suffering from Covid19. For the examinations we used a 3-9 MHz probe and a high-end ultrasound device. The examination was performed in a lying position and under quiet conditions. Before examination we practiced inhalation and exhalation as well as "pressing" or coughing with the patients, which resulted in a physiological closure of the venous valves. To rule out thrombosis, we carried out compression sonography on the legs. During the examination we documented the B-scan, the Color-Coded Duplex Sonography, the HR-flow and the V-flow for 3 seconds at the estuary of the crosses and incorporated these parameters into our measurements. Via V-flow, vectors can be imaged by representing the flow of erythrocytes and visually indicate a possible insufficiency due to delayed or incomplete valve closure. RESULTS: 31 of 50 patients (age 19-81years) showed a complete valve closure of the crosses, three of them suffered from thrombosis. In eight of the 50 study participants (age 45-79 years) a delayed valve closure could be diagnosed by V-flow within 1-2 seconds. None of them had a thrombosis, but six of them suffered from cancer. In eleven patients we derived an incomplete valve closure with insufficiency (age 51-88 years). With reflux it took >2 seconds to close the valve. The patient with Covid19 also showed an incomplete valve closure with insufficiency. At the same time this patient showed a Covid19-associated deep vein thrombosis. Eight additional patients also had a thrombosis. Six of them suffered from cancer. Overall, the results were best visualized by V-Flow. CONCLUSION: The crosse as a significant venous structure can be well investigated by V-flow with respect to hemodynamic changes and a resulted reflux. Also associated changes close to the valve can be visualized well.

Effects of gut microbial metabolite trimethylamine N-oxide (TMAO) on platelets and endothelial cells.

Thrombotic events result from different pathologies and are the underlying causes of severe diseases like stroke or myocardial infarction. Recent basic research now revealed a link between food uptake, food conversion and gut metabolism. Gut microbial production of trimethylamine N-oxide (TMAO) from dietary nutrients like choline, lecithin and L-carnitine was associated with the development of cardiovascular diseases. Within this review we give a systematic overview about the influence of TMAO on blood components like platelets and endothelial cells which both are involved as key players in thrombotic processes. In summary, a mechanistic correlation between the gut microbiome, TMAO and cardiovascular diseases becomes obvious and emphasizes to the significance of the intestinal microbiome.

Contrast-enhanced ultrasound with perfusion analysis in patients with venous malformations before and after percutaneous treatment with ethanol-gel.

INTRODUCTION: Percutaneous sclerotherapy is a well-established treatment option for venous malformations (VM). A recently established sclerosing agent is ethanol-gel. Aim of this study was to identify, if contrast-enhanced ultrasound (CEUS) with an integrated perfusion analysis allows for differentiation between untreated VM, healthy tissue, and with gelified ethanol treated malformation tissue. MATERIAL AND METHODS: In this institutional review board approved prospective study symptomatic VM patients underwent CEUS at exactly the same position before and after sclerotherapy with ethanol-gel. Two experienced sonographers performed all examinations after the bolus injection of microbubbles using a multi-frequency probe with 6 -9 MHz of a high-end ultrasound machine. An integrated perfusion analysis was applied in the center of the VM and in healthy, surrounding tissue. For both regions peak enhancement (peak), time to peak (TTP), area under the curve (AUC), and mean transit time (MTT) were evaluated. Wilcoxon signed rank test was executed; p-values <0.05 were regarded statistically significant. RESULTS: In 23 patients including children (mean age 25.3 years, 19 females) before treatment all identified parameters were significantly higher in the VM center compared to healthy tissue (peak: p < 0.01; TTP: p < 0.01; AUC: p < 0.01; MTT: p < 0.01). Comparing the VM center before and after treatment, TTP (p < 0.02) and MTT (p < 0.01) reduced significantly after sclerotherapy. In surrounding tissue only peak changed after treatment in comparison to pre-treatment results (p = 0.04). Comparing data in the VM center with surrounding tissue after sclerotherapy, results still differed significantly for peak (p < 0.01), TTP (p < 0.01), and AUC (p < 0.01), but assimilated for MTT (p = 0.07). CONCLUSION: All with CEUS identified parameters seem to be excellent tools for differentiating between VM and healthy tissue. TTP and MTT could distinguish between with ethanol-gel sclerotized VM portions and untreated malformation parts and thereby might assist the monitoring of sclerotherapy with ethanol-gel.