Echinococcus multilocularis and other zoonotic helminths in red foxes (Vulpes vulpes) from a southern German hotspot for human alveolar echinococcosis.

BACKGROUND: We describe the spatial distribution of Echinococcus multilocularis in its main definitive host, the red fox, and the distribution of human cases of alveolar echinococcosis (AE) within a highly endemic focus in southern Germany (13.7-19.9/100,000 in 1992-2018). Human cases were unequally distributed within the endemicity focus. The purpose of the study was to test whether this is reflected in the small-scale distribution of E. multilocularis in foxes. METHODS: Three areas with contrasting numbers of human cases were selected within the counties of Ravensburg and Alb-Donau, Baden-Württemberg, Germany. From 2018 to 2020, a total of 240 fox carcasses were obtained from traditional hunters in these areas. Carcasses were necropsied and examined for the presence of intestinal helminths. The statistical analysis was performed with SAS version 9.4, and the geo-mapping with QGIS version 3.16.0 Hannover. RESULTS: The prevalence of E. multilocularis in foxes was 44/106 (41.5%) in area I (commune Leutkirch and environs), 30/59 (50.8%) in area II (commune Isny and environs), and 31/75 (41.3%) in area III (commune Ehingen and environs). From 1992 to 2018, a total of nine human cases of alveolar echinococcosis were recorded in area I, five cases were recorded in study area III, and no cases were recorded in area II. No statistically significant differences between the areas were observed (P > 0.05) for intestinal infections with E. multilocularis, and no apparent spatial correlation with the small-scale distribution of human cases was found. Concerning other zoonotic helminths, Toxocara spp. were equally common, with prevalence of 38.7%, 47.4% and 48.0%, respectively, while the frequency of Alaria alata varied among the study areas (0.0-9.4%), probably reflecting the specific habitat requirements for the establishment of its complex life cycle. CONCLUSIONS: Echinococcus multilocularis is highly prevalent in foxes in all the studied areas. The varying number of human AE cases within these areas should therefore be caused by factors other than the intensity of parasite transmission in foxes.

An optimized protocol for isolation of hepatic leukocytes retrieved from murine and NASH liver biopsies.

Immune dysregulation and inflammation by hepatic-resident leukocytes is considered a key step in disease progression of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis toward cirrhosis and hepatocellular carcinoma. Here, we provide a protocol for isolation and characterization of liver-resident immune cells from fine-needle biopsies obtained from a rodent model and humans. We describe steps for isolating leukocytes, cell sorting, and RNA extraction and sequencing. We then detail procedures for low-input mRNA sequencing analyses.

[Diagnostic delaying factors in hepatic alveolar echinococcosis]. / Diagnoseverzögernde Faktoren bei hepatischer alveolärer Echinokokkose.

PURPOSE: The purpose of this study was to analyze the diagnostic workflow of patients with alveolar echinococcosis (AE) and to identify possible diagnosis-delaying factors. METHODS: The number and type of diagnostic procedures of patients diagnosed with alveolar echinococcosis were investigated. The disease history was recorded on the basis of questionnaires, the available findings, and data supplements from the hospital information system (SAP). Statistical analyses were performed using SAS version 9.4 and Microsoft Excel version 16.43. The study population of the cross-sectional study included n = 109 patients with confirmed alveolar echinococcosis. RESULTS: The definitive diagnosis of alveolar echinococcosis of the liver was made at 26.5 ± 65.0 (mean ± standard deviation) months (min - max: 0 - 344, median = 3). The majority of patients were diagnosed because of incidental imaging findings of the liver (n = 74/109 (67.9%)). A total of n = 56/74 (75.7%) of all incidental findings were diagnosed in an outpatient setting, while n = 15/74 (20.3%) of cases were diagnosed during inpatient hospitalization. On average, 1.1 ± 1.2 (0-11, median = 1) ionizing imaging modalities were used for each patient. Contrast-enhanced sonography was received by 0.3 ± 0.5 (0-2, median = 0) patients. Almost all patients (n = 104/109 (95.4%) had at least one suspected hepatic or extrahepatic malignancy at some time. Exclusion of suspected malignancy occurred at a mean of 4.1 ± 16.5 months (0 -133.8, median = 1). CONCLUSIONS: The diagnostic clarification process of AE patients is lengthy and stressful. The psychological burden of a questionable malignant diagnosis is considerable. Early use of contrast-enhanced sonography and, if necessary, puncture of unclear hepatic masses helps to shorten the difficult diagnostic process.

Contrast-enhanced ultrasound (CEUS) in patients with metastasis-like hepatic alveolar echinococcosis: a cohort study.

PURPOSE: Hepatic alveolar echinococcosis (HAE) of the metastasis-like pattern, according to the Echinococcus Ulm classification, is usually discovered as an incidental finding, and the diagnostic differentiation from "true metastases" is difficult. The aim of this study was to investigate whether lesions of the "metastasis-like pattern" in HAE show a typical contrast behavior that can be used for differentiation from metastasis in malignancies. METHODS: This prospective clinical study included 11 patients with histologically confirmed HAE of the metastasis-like pattern (7 female and 4 male; mean age, 57.1 years; mean disease duration, 59.5 months), who had been examined by B-scan sonography and CEUS, from the National Echinococcosis Registry Germany. RESULTS: On contrast-enhanced sonography, 11/11 reference lesions showed annular rim enhancement in the arterial and portal venous phases. Throughout the entire 4-min study period, none of the reference lesions showed central contrast enhancement-i.e., all exhibited a complete "black hole sign". A small central scar was seen in 81.8% of cases. CONCLUSION: In clinically unremarkable patients with incidentally detected metastasis-like lesions of the liver, contrast-enhanced sonographic detection of rim enhancement without central contrast uptake (black hole sign) should be considered evidence supporting a diagnosis of hepatic alveolar echinococcosis with a rare metastasis-like pattern. This can help to differentiate HAE from metastases, especially in high-endemic areas.

Differentiation of hepatic alveolar echinococcosis with a hemangioma-like pattern compared to typical liver hemangioma using contrast-enhanced ultrasound: a pilot study.

PURPOSE: Echinococcus multilocularis infects humans as a false intermediate host, primarily with intrahepatic manifestation. Incorrect diagnostic interpretation of these liver tumors, especially the hemangioma-like pattern, can lead to progressive disease. The aim of the study was to investigate the differentiation of typical hemangioma and a hemangioma-like pattern of E. multilocularis using contrast-enhanced ultrasound (CEUS). METHODS: This prospective clinical pilot study comprised patients with hemangioma (n = 14) and patients with alveolar echinococcosis (AE) and hemangioma-like pattern (n = 7). Inclusion criteria were the detection of a liver lesion according to a hemangioma-like pattern on E. multilocularis Ulm classification-ultrasound (EMUC-US) and "confirmed" or "probable" AE according to WHO case definition. The comparison group had hepatic hemangioma with typical B-scan sonographic morphology. All participants underwent conventional and contrast-enhanced ultrasonography. RESULTS: The patient group comprised five men (71.4%) and two women (28.6%) with a mean average age of 64.1 ± 11.2 years. The patient group with hemangioma comprised nine female subjects (64.3%) and five male subjects (35.7%) with a mean average age of 56.1 ± 12.0 years. Early arterial bulbous ring enhancement (p < 0.0001) and iris diaphragm phenomenon could only be visualized in the patients with hemangioma (p < 0.0001). Furthermore, the patients with hemangioma exhibited hyperenhancement in the late phase (p = 0.0003). In contrast, the patients exhibited typical early arterial rim enhancement (p < 0.0001) and, in the portal venous and late phase, complete or incomplete non-enhancement (black hole sign; p = 0.0004). CONSLUSION: The behavior of hemangioma-like AE lesions and typical liver hemangiomas is significantly different on CEUS. AE should be considered as a possible differential diagnosis, especially in high-endemic areas.

[Spread and Development of Alveolar Echinococcosis in Germany, 1992-2018]. / Untersuchung zur Ausbreitung und Entwicklung der alveolären Echinokokkose in Deutschland, 1992­2018.

GOAL OF THE STUDY: Alveolar echinococcosis (AE) is a rare parasitosis caused by the pathogen Echinococcus multilocularis. There is an increase in the number of cases in many countries. The aim of the study was to investigate the current prevalence and the change in the geographical distribution pattern. METHODOLOGY: Data were collected retrospectively for the period 1992-2018 using the registered cases in the national disease register for AE in Germany. Statistical analysis was performed using the SAS statistical analysis system version 9.4 (SAS Institute, Cary, N.C., USA). RESULTS: The study population of n=569 patients included n=322 (56,59%) women and n=247 (43,40%) men. The mean average age of patients with alveolar echinococcosis at first presentation was 53,90±17,54 years (median: 56,00 years). The Moran's I test statistic showed a positive spatial autocorrelation for the period 1992-2018 corresponding to a heterogeneous distribution of disease cases in Germany (I=0,4165; Z=10,9591, p=0,001). An increase in age- and sex-specific prevalence could be determined for the entire study period (1992-2018). The overall prevalence in the period 1992-2018 was 0,71 cases per 100,000 population. The determination of the prevalence for the period 1992-2018 resulted in 0,31 cases for men and 0,40 cases for women per 100,000 population. In the period 1992-1996, no AE cases had been registered in 11/16 (68,8%) federal states (Berlin, Brandenburg, Bremen, Hamburg, Mecklenburg-Vorpommern, Rheinland-Pfalz, Saarland, Sachsen, Sachsen-Anhalt, Schleswig-Holstein und Thüringen). The evaluation recently shows an increased occurrence of cases in the federal states of Hessen, Rheinland-Pfalz and Nordrhein-Westfalen. CONCLUSIONS: The analysis shows a rise in prevalence and an increasing number of cases outside the classic endemic areas of Baden-Württemberg and Bavaria.

Dog Ownership and Risk for Alveolar Echinococcosis, Germany.

Human alveolar echinococcosis is caused by the parasite Echinococcus multilocularis, and dog ownership has been identified as a risk factor. We sought to specify the factors of dog ownership underlying this risk by conducting a case-control study among dog owners in Germany. The analysis revealed an increased odds ratio of ≈7-fold for dog owners whose dogs roam unattended in fields, 13-fold for dog owners who feed their dogs organic waste daily, 4-fold for dog owners who take their dog to a veterinarian only in case of illness, and 10-fold for dog owners who have never been informed by a veterinarian about the risk for infection. The results highlight the risk for infection associated with various factors of dog ownership and the value of veterinarians informing owners about prevention.

Comparison of superb microvascular imaging (SMI) quantified with ImageJ to quantified contrast-enhanced ultrasound (qCEUS) in liver metastases-a pilot study.

Background: The aim of the study was to compare methods for the assessment of vascularisation of liver metastases (LM) between superb microvascular imaging (SMI), contrast-enhanced ultrasound, and microvascular density (MVD). Methods: SMI results were quantified as the vascularisation quotient (VQ), based on a grey-scale analysis with ImageJ image software. Those results were compared to contrast-enhanced ultrasonography (CEUS) values, calculated with VueBox®. MVD was measured with an anti-CD34 antibody. Results: This study included 13 patients with LM. The VQ showed a strong correlation with the quantified parameters of contrast-enhanced ultrasound. The parameters of quantified contrast-enhanced ultrasound compared with quantified SMI showed the following statistical correlations: peak enhancement (PE), in arbitrary unit (a.u.) (r=0.72104, P=0.0054), PE in Decibel (dB) (r=0.65918, P=0.00141), Wash-in- Area Under the Curve (WiAUC) in a.u. (r=0.63604, P=0.00194), Wash-in Perfusion-Index (WiPI) in a.u. (r=0.73337, P=0.0043), Wash-in Perfusion-Index (WiPI) in dB (r=0.65642, P=0.0194), Wash-in-Rate (WiR) in a.u. (r=0.7304, P=0.0036) and Wash-in-Rate (WiR) in dB (r=0.82897, P=0.0005). Conclusions: Comparison of the two methods, SMI and contrast-enhanced ultrasound (CEUS), for quantitative assessment of vascularisation of LM showed good correlation. The contrast-independent Doppler technique SMI can qualitatively assess the vascularisation of LM.

Echinococcosis: a Challenge for Liver Sonography.

The sonographic findings in alveolar echinococcosis (AE) and cystic echinococcosis (CE) are complex and can pose significant differential diagnostic problems. They may present like complicated cysts or malignant tumors in the liver. We will discuss the diagnostic difficulties and pitfalls of these two diseases based on case histories.

Stage-Oriented CT Classification and Intermodal Evolution Model in Hepatic Alveolar Echinococcosis. / Stadienorientierte CT-Klassifikation und intermodales Evolutionsmodell bei hepatischer alveolärer Echinokokkose.

BACKGROUND: Alveolar echinococcosis (AE) is one of the most dangerous human parasitoses. The main site of disease manifestation is the liver (about 98 %). The Echinococcus Multilocularis Ulm Classification for Computed Tomography (EMUC-CT), presented in 2016, was the first compilation of CT morphological criteria of hepatic AE. Studies based on EMUC-CT made it possible to draw conclusions about the development of the lesions in the course of disease beyond purely diagnostic typing. Among the most important findings of these precursor studies was that EMUC-CT type IV presented as an initial lesion, whereas EMUC-CT type III lesions were mostly associated with an advanced disease constellation. An intermodal view of image morphological criteria provides further multi-layered indications for lesion evolution. METHOD: With the "Alveolar Echinococcosis Ulm Classification" (AEUC), a revision of the previous EMUC-CT was carried out with stage-oriented reorganization of the primary morphologies. Furthermore, an intermodal classification scheme for the evolution of hepatic AE lesions based on AEUC, MRI Kodama classification, and aspects of ultrasound could be outlined. RESULTS: The first stage-oriented CT classification of hepatic AE "AEUC" is based with respect to its lesion characterization on the separate consideration of two classification pillars, the five "primary morphologies", AEUC I-V (AEUC II-IV with subcriteria) and the five "patterns of calcification". In addition, an intermodal classification scheme presents five stages of lesion evolution: "initial stage", "progressive stage", "advanced stage", "transitional stage" and "regressive stage". CONCLUSION: The imaging modalities differ with respect to their visualization of lesion criteria. This underlines the need for unimodal classification systems. Staging of an AE lesion can be done more accurately by evaluating different modalities. KEY POINTS: · The AEUC provides a stage-oriented CT classification for hepatic AE.. · Aspects of different modalities allow a more multi-layered view of lesion evolution.. · More accurate staging can be achieved by combining different modalities.. CITATION FORMAT: · Graeter T, Schmidberger J. Stage-Oriented CT Classification and Intermodal Evolution Model in Hepatic Alveolar Echinococcosis. Fortschr Röntgenstr 2022; 194: 532 - 544.

Long-term follow-up of liver alveolar echinococcosis using echinococcosis multilocularis ultrasound classification.

BACKGROUND: When Echinococcus multilocularis infects humans as a false intermediate host, alveolar echinococcosis (AE) usually manifests primarily intrahepatically and is initially asymptomatic. If the disease remains undiagnosed and untreated, progressive growth occurs, reminiscent of malignant tumours. The only curative therapy is complete resection, which is limited to localised stages, and palliative drug therapy is used otherwise. Consequently, early diagnosis and reliable detection of AE lesions are important. For this reason, abdominal ultrasonography, as the most common primary imaging for AE, relies on classification systems. AIM: To investigate how hepatic AE lesion sonomorphology changes over time in the Echinococcosis Multilocularis Ulm Classification (EMUC)-ultrasound (US) classification. METHODS: Based on data from Germany's national echinococcosis database, we evaluated clinical and US imaging data for 59 patients according to the AE case definition in our preliminary retrospective longitudinal study. There had to be at least two liver sonographies ≥ 6 mo apart, ≥ 1 hepatic AE lesion, and complete documentation in all US examinations. The minimum interval between two separately evaluated US examinations was 4 wk. The AE reference lesion was the largest hepatic AE lesion at the time of the first US examination. To classify the sonomorphologic pattern, we used EMUC-US. In addition to classifying the findings of the original US examiner, all reference lesions at each examination time point were assigned EMUC-US patterns in a blinded fashion by two investigators experienced in US diagnosis. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, United Stated). P values < 0.05 were considered statistically significant. RESULTS: The preliminary study included 59 patients, 38 (64.5%) women and 21 (35.6%) men. The mean age at initial diagnosis was 59.9 ± 16.9 years. At the time of initial ultrasonography, a hailstorm pattern was present in 42.4% (25/59) of cases, a hemangioma-like pattern in 16.9% (10/59), a pseudocystic pattern in 15.3% (9/59), and a metastasis-like pattern in 25.4% (15/59). For the hailstorm pattern, the average lesion size was 67.4 ± 26.3 mm. The average lesion size was 113.7 ± 40.8 mm with the pseudocystic pattern and 83.5 ± 27.3 mm with the hemangioma-like pattern. An average lesion size of 21.7 ± 11.0 mm was determined for the metastasis-like pattern. Although the sonomorphologic pattern remained unchanged in 84.7% (50/59) of AE reference lesions, 15.3% (9/59) showed a change over time. A change in pattern was seen exclusively for AE lesions initially classified as hemangioma-like or pseudocystic. A total of 70% (7/10) of AE lesions initially classified as hemangioma-like showed a relevant change in pattern over time, and 85.7% (6/7) of these were secondarily classified as having a hailstorm pattern, with the remainder (1/7; 14.3%) classified as having a pseudocystic pattern. A total of 22.2% (2/9) of AE lesions initially classified as pseudocystic showed a relevant change in pattern over time and were classified as having a hailstorm pattern. For AE lesions initially classified as having a hailstorm or metastatic pattern, no pattern change was evident. All patients with pattern change were on continuous drug therapy with albendazole. CONCLUSION: The sonomorphology of hepatic AE lesions may change over time. The hemangioma-like and pseudocystic patterns are affected.

Analysis of vascularization in thyroid gland nodes with superb microvascular imaging (SMI) and CD34 expression histology: a pilot study.

BACKGROUND: The Doppler sonography technique known as "superb microvascular imaging" (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation. METHODS: We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations. RESULTS: Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260). CONCLUSION: We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes.

Elasticity standard values of the thoracolumbar fascia assessed with acoustic radiation force impulse elastography on healthy volunteers: A cross section study.

INTRODUCTION: Determining the normal values for acoustic radiation force impulse (ARFI) shear wave elastography of the thoracolumbar fascia (TLF) and define possible factors of influence. METHODS: We measured the shear wave velocity (SWV) in m/s and the diameter (anterior-posterior) in mm of the TLF bilateral in 267 healthy participants with the Acuson S3000™ (Siemens) using the virtual touch image quantification mode (VTIQ). The parameters were tested for correlations with the anthropometric data of the participants, between different age groups and the genders, as well as information obtained from the history, such as smoking and sporting activities. RESULTS: We determined a mean SWV of 3.28 ±â€¯0.55 m/s for the left thoracolumbar fascia and 3.44 ±â€¯0.55 m/s for the right. The diameter on the right was 2.7 ±â€¯0.8 mm. On the left, it was 2.7 ±â€¯0.9 mm. Neither body mass index (BMI) nor gender had a significant effect on either of the measured parameters (p > 0.05). The same goes for regular medication, sporting activity or the consumption of alcohol (p > 0.05). The results concerning the effect of smoking and age were inconclusive as they only had a significant influence to either the right or the left side of the TLF but not on the other side. CONCLUSIONS: We collected the normal value for ARFI shear wave elastography of the TLF in 267 healthy participants. Furthermore, neither gender, BMI, sports activity nor the consumption of alcohol affected the elasticity or the diameter of the thoracolumbar fascia.

[An Update on the Epidemiological Situation of Alveolar Echinococcosis: Recording and Reporting Structures in Austria, Switzerland and Germany]. / Epidemiologisches Update: Aktuelles zur epidemiologischen Situation der alveolären Echinokokkose und deren Erfassungs- und Meldestrukturen in Österreich, der Schweiz und Deutschland.

OBJECTIVE: Alveolar echinococcosis (AE) is a rare disease in Austria, Switzerland and Germany (DACh) caused by an infection with the parasite Echinococcus multilocularis. The aim of the study was to describe differences in the detection and reporting systems of alveolar echinococcosis in Austria, Switzerland and Germany and to describe epidemiological trends. METHODOLOGY: As part of an epidemiological update on 6th September 2019 in Ulm, Germany, experts and representatives discussed differences in the reporting and recording systems as well as the current epidemiological situation. RESULTS: Since 2004, Austria has had an obligation to report suspected cases, diseases and deaths of alveolar echinococcosis by name in accordance with §1 Para. 1 of the Epidemiegesetz 1950 (EpidemieG) and the Ordinance on Notifiable Communicable Diseases. According to §7 Para. 3 of the German Infection Protection Act (IfSG), Germany has also been subject to a reporting obligation since 2001, but not by name. In addition, national registers are available in both countries, which can be used to answer scientific questions. In Switzerland, there is no obligation to report human alveolar echinococcosis since 1997. Efforts are currently being made to implement a national register for alveolar echinococcosis in Switzerland. Despite different reporting and recording systems, a similar epidemiological trend can be observed for DACh. CONCLUSIONS: In Austria, Switzerland and Germany there is a slightly increasing trend of human cases with alveolar echinococcosis. The direct comparability is limited due to different reporting obligations. The structures often do not allow a joint answering of scientific questions concerning diagnostics, treatment and care.

Intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis: a multicenter cohort study.

BACKGROUND: The main endemic areas of alveolar echinococcosis (AE) are in central Europe and western China. The infiltration of intrahepatic vascular and bile ducts as well as extrahepatic disease can lead to complications and may increase morbidity in AE. PURPOSE: To evaluate the vascular/biliary involvement of hepatic alveolar echinococcosis (HAE) and distant extrahepatic disease at each of four locations in Germany, France, and China. MATERIAL AND METHODS: Contrast-enhanced abdominal magnetic resonance imaging (MRI) scans of patients with HAE, 200 in total, were evaluated by five examiners. AE liver lesions were classified according to Kodama's classification. Furthermore, distant extrahepatic manifestations were documented with additionally performed imaging modalities. Vascular/biliary involvement of hepatic manifestations as well as the presence of extrahepatic manifestations were correlated with the respective Kodama type of the liver lesion. RESULTS: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (12/100 vs. 3/100; Fisher's exact test: P=0.0286). A significant relationship exists between presence of distant extrahepatic disease manifestation and size of the AE liver lesion (132.53 ± 48.65 vs. 92.49 ± 50.06; P = 0.0030). Vascular/biliary involvement is significantly more frequent in China than in Europe (86/100 vs. 65/100; χ2 = 11.92; P = 0.0006). Vascular/biliary involvement depends on lesion size (111.10 ± 47.44 vs. 47.36 ± 24.36; P<0.0001). Different types of AE liver lesions are associated with differences in vascular/biliary involvement and extrahepatic manifestations. CONCLUSION: Vascular/biliary involvement and presence of distant extrahepatic manifestations depend on size of the HAE lesions and are more frequently detected in China. Different MRI morphological patterns influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.

Ultrasound 2020 - Diagnostics & Therapy: On the Way to Multimodal Ultrasound: Contrast-Enhanced Ultrasound (CEUS), Microvascular Doppler Techniques, Fusion Imaging, Sonoelastography, Interventional Sonography. / Ultraschall 2020 ­ Diagnostik & Therapie: Auf dem Weg zur multimodalen Sonografie: kontrastverstärkter Ultraschall (CEUS), mikrovaskuläre Dopplerverfahren, Fusionsbildgebung, Sono-Elastografie, interventionelle Sonografie.

BACKGROUND: Ultrasound as a non-ionizing imaging procedure is one of the most important diagnostic procedures in everyday clinical practice. The technology is widely used. Due to constant technical innovations, sonographic procedures, such as contrast-enhanced ultrasound (CEUS), sonoelastography, new microvascular Doppler modalities and, as an example of interventional procedures, sonographically controlled microwave ablation (MWA), are becoming increasingly important in diagnostic imaging and interventional medicine alongside CT and MRI. However, this also requires greater expertise, specialization and qualification on the part of users. METHOD: This review article provides information about the range of technical innovations in ultrasound in recent years and describes the underlying technology, the clinical applications, and their diagnostic value. These are presented in the context of the current literature, explaining their advantages and disadvantages and their clinical value. RESULTS AND CONCLUSION: Contrast-enhanced ultrasound (CEUS), microvascular Doppler modalities, fusion imaging and elastography complement B-scan ultrasound and conventional Doppler procedures for various problems. Microwave ablation (MWA) has a firm place as an ablative procedure for local tumor therapy in different organ systems and can be performed under ultrasound guidance. Thanks to new developments, the possibilities of ultrasound are now greater than ever. Knowledge of the technology, indications, and possible applications of newer procedures is essential for adequate patient care. KEY POINTS: · Contrast-enhanced ultrasound (CEUS) allows an increase in sensitivity and specificity in the assessment of parenchymal lesions.. · CEUS allows the microperfusion to be visualized and quantified. For larger vessels, CEUS is an important instrument in diagnosing endoleak after stenting.. · Microvascular Doppler techniques with clutter suppression algorithms allow a more accurate representation of the smallest vessels than regular color or power Doppler.. · Elastography of the liver in diffuse hepatopathies is a noninvasive diagnostic tool to exclude higher grade fibrosis/cirrhosis.. · Microwave ablation (MWA) also offers sonographically controlled ablation of tumors.. CITATION FORMAT: · Kloth C, Kratzer W, Schmidberger J et al. Ultrasound 2020 - Diagnostics & Therapy: On the Way to Multimodal Ultrasound: Contrast-Enhanced Ultrasound (CEUS), Microvascular Doppler Techniques, Fusion Imaging, Sonoelastography, Interventional Sonography . Fortschr Röntgenstr 2021; 193: 23 - 32.

Immunohistological detection of small particles of Echinococcus multilocularis and Echinococcus granulosus in lymph nodes is associated with enlarged lymph nodes in alveolar and cystic echinococcosis.

BACKGROUND: Alveolar (AE) and cystic echinococcosis (CE) in humans are caused by the metacestode of the tapeworms Echinococcus multilocularis and Echinococcus granulosus sensu lato (s.l.). Immunohistochemistry with the monoclonal antibodies (mAb) Em2G11, specific for AE, and the mAb EmG3, specific for AE and CE, is an important pillar of the histological diagnosis of these two infections. Our aim was to further evaluate mAb EmG3 in a diagnostic setting and to analyze in detail the localization, distribution, and impact of small particles of Echinococcus multilocularis (spems) and small particles of Echinococcus granulosus s.l. (spegs) on lymph nodes. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the mAb EmG3 in a cohort of formalin-fixed, paraffin embedded (FFPE) specimens of AE (n = 360) and CE (n = 178). These samples originated from 156 AE-patients and 77 CE-patients. mAb EmG3 showed a specific staining of the metacestode stadium of E. multilocularis and E. granulosus s.l. and had a higher sensitivity for spems than mAb Em2G11. Furthermore, we detected spegs in the surrounding host tissue and in almost all tested lymph nodes (39/41) of infected patients. 38/47 lymph nodes of AE showed a positive reaction for spems with mAb EmG3, whereas 29/47 tested positive when stained with mAb Em2G11. Spegs were detected in the germinal centers, co-located with CD23-positive follicular dendritic cells, and were present in the sinuses. Likewise, lymph nodes with spems and spegs in AE and CE were significantly enlarged in size in comparison to the control group. CONCLUSIONS/SIGNIFICANCE: mAb EmG3 is specific for AE and CE and is a valuable tool in the histological diagnosis of echinococcosis. Based on the observed staining patterns, we hypothesize that the interaction between parasite and host is not restricted to the main lesion since spegs are detected in lymph nodes. Moreover, in AE the number of spems-affected lymph nodes is higher than previously assumed. The enlargement of lymph nodes with spems and spegs points to an immunological interaction with the small immunogenic particles (spems and spegs) of Echinococcus spp.

Evaluation of intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis.

BACKGROUND: The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE. AIM: To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim. METHODS: Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations (n = 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States). RESULTS: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (P = 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size (P = 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe (P < 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III (P < 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III. CONCLUSION: Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation.

Distribution of alveolar echinococcosis according to environmental and geographical factors in Germany, 1992-2018.

Alveolar echinococcosis (AE) is a rare zoonotic disease caused by the larval stage of Echinococcus multilocularis. Despite its low world-wide prevalence, this disease shows differences in the regional distribution of cases. In the present cohort study, we analyse the distribution of AE according to environmental and geographical factors in Germany. We identified the place of residence of 591 cases of AE from the national database for AE, and georeferenced these localities in the Universal Transverse Mercator coordinate system. Data on elevation, air temperature, precipitation height and land cover were mapped out and correlated with the distribution of cases of disease during the period 1992-2018. Moran's I statistic was used for spatial autocorrelation. Differences in frequency distribution between elevation, air temperature, precipitation height and landscape feature classes were analysed with the Kruskal-Wallis test. With the multiple linear regression analysis, we determined the influences and interactions of geographical and climatic factors on the number of AE cases. The results showed a heterogeneous distribution of AE cases with a higher concentration in southern Germany than in the rest of Germany (I = 0.225517, Z = 35.8182 and p < 0.001). There was a statistically significant difference in frequency distribution between precipitation height, air temperature, elevation and landscape feature classes and AE cases in Germany (p < 0.0001). In regions with higher elevations (505-672 m), moderate average air temperatures (6.0-7.9°C) and higher precipitation rates (701-1000 mm) most AE cases were recorded. It seems, that regions with higher precipitation rates, higher elevations and moderate average air temperatures have a higher infection burden and infection conditions. It is therefore extremely important to generate greater awareness of the disease in these regions, with the aim of recognising potential cases of AE as early as possible and introducing the appropriate therapeutic measures.

Hepatic alveolar echinococcosis: correlation between computed tomography morphology and inflammatory activity in positron emission tomography.

Positron emission tomography-computed tomography (PET-CT) with 18F-fluorodesoxyglucose (FDG) is the imaging modality of choice for assessing inflammation surrounding hepatic alveolar echinococcosis (AE) lesions. This study is the first to evaluate FDG uptake in hepatic AE (n = 51) based on the standardized uptake value (SUV) and to correlate the SUVs with primary morphology and calcification patterns, based on the Echinococcus multilocularis Ulm Classification for Computed-Tomography (EMUC-CT). Our results show that the SUVs were increased for lesions with EMUC-CT types I-IV primary morphology, compared to the surrounding healthy liver tissue (SUV = 2.5 ± 0.4; p < 0.05). Type IV lesions included, by far, the highest number of PET-negative lesions. A comparison of lesions with different primary morphologies showed clear differences. The highest SUVs were found for types I and III, and the lowest was found for type IV. Type IV lesions (SUV, 3.8 ± 1.5) showed significantly lower uptake compared to type I (SUV, 6.9 ± 3.5; p = 0.030) and type III (SUV, 7.4 ± 3.9; p = 0.031) lesions. For type II lesions, the results showed only a statistical trend (SUV, 6.1 ± 3.1; p = 0.073). Due to the small number of cases, an evaluation of type V (n = 1) lesions was not possible. The different SUVs of lesions with different primary morphologies, particularly the lower FDG uptake observed in type IV lesions, suggested that these SUVs might reflect different stages of the disease.