Contrast-enhanced ultrasound (CEUS) and gallbladder diseases - A retrospective mono-center analysis of imaging findings with histopathological correlation.

BACKGROUND: Radiologic imaging, especially ultrasound has an important role in the assessment of gallbladder alteration. Contrast-enhanced ultrasound (CEUS) is an easy and fast imaging technique that overcomes the limitations of greyscale ultrasonography. It is a safe tool that can be used as an additional imaging modality in order to elucidate and differentiate gallbladder pathological findings. OBJECTIVE: The aim of this retrospective study analysis is to assess the diagnostic performance of CEUS in gallbladder alterations and compare the results to the histopathological findings. METHODS: A total of 17 patients between 2009 and 2017 with uncertain gallbladder appearance were retrospectively analysed. A single experienced physician with more than fifteen years' experience performed CEUS examinations by applying a second-generation blood pool agent (SonoVue®, Bracco, Milan, Italy). Archived images were interpreted by the same physician and compared to the histopathological findings. RESULTS: CEUS results, when correlated to the respectively pathologic findings, presented a sensitivity of 100%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%. All patients were successfully examined without any adverse reaction. CONCLUSION: In conclusion, the excellent results in this study acknowledged that CEUS is a feasible alternative tool to differentiate gallbladder pathologic alterations.

Diagnostic performance of contrast-enhanced ultrasound (CEUS) for the evaluation of gallbladder diseases1.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique to conventional ultrasound in order to clarify gallbladder findings, CEUS is easy and fast to perform, overcomes the limitations of gray-scale ultrasonography and is a safe tool. OBJECTIVE: The aim of this retrospective mono-center analysis study is to evaluate the diagnostic performance of CEUS in the assessment of gallbladder disease by comparing its results with additional CT findings. METHODS: A total of 24 patients between 2009 and 2017 with unclear gallbladder appearance were retrospectively analysed. The contrast agent administered was a second-generation blood pool agent (SonoVue®, Bracco, Milan, Italy). Examinations were performed and interpreted by a single experienced radiologist with more than fifteen years' experience. RESULTS: 24 patients were successfully examined without any adverse reaction. CEUS presented a sensitivity of 75%, a specificity of 100.0%, a positive predictive value of 100.0% and a negative predictive value of 95%. CONCLUSIONS: In conclusion, the excellent results in this study acknowledged that CEUS is a feasible alternative tool to differentiate gallbladder pathologic alterations.

Preoperative Embolization to Improve the Surgical Management and Outcome of Juvenile Nasopharyngeal Angiofibroma (JNA) in a Single Center: 10-Year Experience.

PURPOSE: Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign neoplasm that occurs almost exclusively in the nasopharynx of adolescent male individuals. METHODS: We performed a retrospective study to determine the efficacy and safety of preoperative embolization and the surgical outcome in patients with JNA in a single-center institution. Fifteen cases undergoing embolization and surgical treatment between April 2003 and February 2013 were evaluated retrospectively. The demographic data, clinical presentation, and treatment were reviewed including the kind of preoperative embolization and different surgical approaches performed. The parameters investigated were the amount of blood loss, the tumor stage, and the rates of recurrence. Subsequently, a comparison was made between patients who had undergone Onyx® embolization versus those who had been embolized with the standard approach. RESULTS: In these 15 patients (mean age, 15 years), a total of 27 surgical procedures were performed. One patient was at stage Ia, two were at stage Ib, two were at stage IIa, six were at stage IIb, one was at stage IIc, and three were at stage IIIa based on the Radkowsky classification. All patients underwent preoperative embolization and subsequent surgery. The surgical approach and the embolization technique varied and evolved during time. The embolization procedure decreased the intraoperative blood loss to a minimum of 250 ml, and with the advent of intratumoral embolization, the rate of recurrence diminished. CONCLUSION: Preoperative Onyx® embolization facilitates the shift in the treatment to endoscopic excision in selected patients, which reduces recurrence rates and overall morbidity.

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

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

Evaluation of multimodality imaging using image fusion with ultrasound tissue elasticity imaging in an experimental animal model.

PURPOSE: To evaluate the ultrasound tissue elasticity imaging by comparison to multimodality imaging using image fusion with Magnetic Resonance Imaging (MRI) and conventional grey scale imaging with additional elasticity-ultrasound in an experimental small-animal-squamous-cell carcinoma-model for the assessment of tissue morphology. METHOD AND MATERIALS: Human hypopharynx carcinoma cells were subcutaneously injected into the left flank of 12 female athymic nude rats. After 10 days (SD ± 2) of subcutaneous tumor growth, sonographic grey scale including elasticity imaging and MRI measurements were performed using a high-end ultrasound system and a 3T MR. For image fusion the contrast-enhanced MRI DICOM data set was uploaded in the ultrasonic device which has a magnetic field generator, a linear array transducer (6-15 MHz) and a dedicated software package (GE Logic E9), that can detect transducers by means of a positioning system. Conventional grey scale and elasticity imaging were integrated in the image fusion examination. After successful registration and image fusion the registered MR-images were simultaneously shown with the respective ultrasound sectional plane. Data evaluation was performed using the digitally stored video sequence data sets by two experienced radiologist using a modified Tsukuba Elasticity score. The colors "red and green" are assigned for an area of soft tissue, "blue" indicates hard tissue. RESULTS: In all cases a successful image fusion and plan registration with MRI and ultrasound imaging including grey scale and elasticity imaging was possible. The mean tumor volume based on caliper measurements in 3 dimensions was ~323 mm3. 4/12 rats were evaluated with Score I, 5/12 rates were evaluated with Score II, 3/12 rates were evaluated with Score III. There was a close correlation in the fused MRI with existing small necrosis in the tumor. None of the scored II or III lesions was visible by conventional grey scale. CONCLUSION: The comparison of ultrasound tissue elasticity imaging enables a secure differentiation between different tumor tissue areas in comparison to image fusion with MRI in our small study group. Therefore ultrasound tissue elasticity imaging might be used for fast detection of tumor response in the future whereas conventional grey scale imaging alone could not provide the additional information. By using standard, contrast-enhanced MRI images for reliable and reproducible slice positioning, the strongly user-dependent limitation of ultrasound tissue elasticity imaging may be overcome, especially for a comparison between baseline and follow-up measurements.

[HPV-associated oropharyngeal carcinoma. Status quo and relationship with cancer of unknown primary]. / HPV-assoziierte oropharyngeale Karzinome. Aktueller Stand und Verhältnis zum Karzinom unbekannter Herkunft.

Carcinomas of the oropharynx with association to high-risk types of human papillomavirus (HPV) have been identified as a new tumour entity with favourable prognosis, distinct from classical nicotine- and alcohol-associated carcinoma. They develop through oncogenic transformation of the basal cells of reticulated cryptal epithelium of the palatinal tonsils and the base of the tongue. Positivity for HPV strongly correlates with an atypical, non-keratinizing histological differentiation and cystic transformation of lymph node metastases. Strong immunohistological positivity for p16 reliably detects transcriptionally active infection with high-risk HPV. Hence, p16 staining has been regarded as an effectual diagnostic tool in the appropriate setting. Frequent nodal metastasation as well as considerable size of (cystic) metastases, and frequent small size as well as submucosal location of primary tumours all contribute to frequent initial manifestation of cervical cancer of unknown primary (CUP). In a situation of CUP diagnostic testing for HPV (in negative cases in addition to EBV) is recommended in lymph node metastases, due to the high predictive value for the localization of occult primary carcinomas. Intense clinicopathological cooperation is mandatory for improved detection of small, occult primary carcinomas. The relevance of this new carcinoma entity will increase, as the incidence continues to increase worldwide.

Sonography: the leading diagnostic tool for diseases of the salivary glands.

Ultrasound examination is the imaging procedure with the best predictive diagnostic capability for the salivary glands. Due to the salivary glands' relatively superficial anatomical location, clear boundary from surrounding tissue and comparatively typical echogenicity, therefore sonography is ideal for diagnosis. In addition, the technical advances in recent years, including higher resolution, color Doppler sonography, contrast-enhanced ultrasound, elastography, and tissue harmonic have lead to an improvement in diagnostic accuracy of sonography further resulting in an expansion of the range of indications. Sonography allows detection of obstructive salivary gland diseases such as stenosis or sialolithiasis, as well as sialadenosis such as Sjögren syndrome. Ultrasound examination alone is sufficient to diagnose benign tumors. However, in the case of malignant tumors, computer tomography or MRI may be also required, especially to determine the question of infiltration of the skull base.

Comparison of consecutive bolus tracking and flash replenishment measurements for the assessment of tissue hemodynamics using contrast-enhanced ultrasound (CEUS) in an experimental human squamous cell carcinoma model.

PURPOSE: To evaluate "bolus-tracking" (BT) and "flash-replenishment" (FR) for the assessment of tissue hemodynamics by contrast-enhanced ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model. Since the underlying tissue is the same, strong correlations between parameter outcomes of both techniques are expected. METHODS AND MATERIALS: Human hypopharynx-carcinoma-cells were subcutaneously injected into the left flank of 18 female athymic-nude-rats. After 10 days of subcutaneous tumour growth, bolus tracking and flash-replenishment measurements were performed consecutively in the same imaging plane in each rat after bolus-injection of SonoVue via the lateral tail vein using a high-end ultrasound system with a 15 MHz probe. Video-sequences were analysed with dedicated software (VueBox®, Bracco-Suisse®). From BT measurements, the parameters peak enhancement (PEBT), wash-in area-under-the-curve (Wi-AUCBT), mean transit time (MTTBT), wash-in-rate (WiRBT) and perfusion-index (Wi-PIBT) were derived; FR yielded estimates of relative-blood-volume (rBVFR), mean transit time MTTFR, relative blood flow rBFFR and wash-in rate Wi-RFR. RESULTS: In all rats, BT and FR measurements could be completed successfully. Highly significant correlations were observed between rBVFR and PEBT, rBVFR and Wi-AUCBT, rBVFR and MTTBT, rBVFR and WiPIBT, MTTFR and MTTBT, rBFFR and PEBT, rBFFR and Wi-AUCBT, rBFFR and WiRBT, rBFFR and WiPIBT, WiRFR and PEBT, WiRFR and Wi-AUCBT, WiRFR and WiRBT and WiRFR and WiPIBT. CONCLUSION: Whereas bolus tracking can be used in a wide range of modalities including CEUS, CT and MR, FR as a technique for the assessment of tissue hemodynamics is unique to CEUS. Although BT and FR yield different parameters, the underlying tissue hemodynamics are equal. In this work, we were able to demonstrate strong correlations between different parameters of both modalities in a small-animal-tumor-model, indicating that flash-replenishment is a valid alternative to the more established bolus-tracking technique. Although the lack of absolute, quantitative parameters hinders a direct comparison of both modalities, FR and BT should both be suitable for a relative comparison, e.g. between baseline and follow-up examinations.

Elastography: a new diagnostic tool for evaluation of obstructive diseases of the salivary glands; primary results.

PURPOSE: Obstructive diseases of the salivary glands, a common problem in the ENT field, are often based on sialolithiasis but can also result from rare circumstances. Due to recent technical innovations, there has been significant development in the treatment of obstructive diseases of the salivary glands such that minimally invasive glandula-sustaining therapy has now become standard. However, there is still no effective technique to assess and monitor the recovery of the parenchyma of the gland. As a result, recurrent infections often lead to modification of the gland in which fibrosis increases and the gland becomes coarse. After treatment, the parenchyma of the gland is able to recover. Thus, to more effectively monitor and promote the success of treatment, we have developed a new method to measure and quantify the stiffness of the glandula tissue using elastography (Virtual Touch TM Application) to assess the degree of recovery. MATERIALS AND METHODS: First, we collected elastography data from 30 healthy volunteers as part of a conventional ultrasound (Siemens, ACUSON, S 2000, Germany) with a multi-frequency linear 9 MHz transducer in order to determine if normal findings are sufficiently quantifiable. We subsequently measured patients with sialolithiasis of the submandibular gland. RESULTS: For healthy volunteers, the average value was 1.96 ± 0.48 m/s for the glandula submandibularis and 2.66+/- 0.89 for the parotid gland, a statistically significant difference. For patients with sialolithiasis of the submandibular gland, the average value was 2.98 ± 0.4 m/s, a highly significant difference in comparison to the healthy side of the patient. CONCLUSION: Elastography is an easy to use diagnostic method that shows promise to become a valuable tool for the assessment of disease severity as it provides the possibility to quantify the level of treatment benefit for the patient.

[Ultrasound-guided image fusion with computed tomography and magnetic resonance imaging. Clinical utility for imaging and interventional diagnostics of hepatic lesions]. / Ultraschallgestützte Bildfusion mittels CT und MRT. Klinische Bedeutung für die bildgebende und interventionelle Diagnostik von Leberläsionen.

Abdominal ultrasound is often the first-line imaging modality for assessing focal liver lesions. Due to various new ultrasound techniques, such as image fusion, global positioning system (GPS) tracking and needle tracking guided biopsy, abdominal ultrasound now has great potential regarding detection, characterization and treatment of focal liver lesions. Furthermore, these new techniques will help to improve the clinical management of patients before and during interventional procedures. This article presents the principle and clinical impact of recently developed techniques in the field of ultrasound, e.g. image fusion, GPS tracking and needle tracking guided biopsy and discusses the results based on a feasibility study on 20 patients with focal hepatic lesions.

[Contrast-enhanced ultrasound in animal models]. / Kontrastverstärkter Ultraschall der Skelettmuskulatur.

In the past the detection of tumor perfusion was achieved solely via invasive procedures, such as intravital microscopy or with the help of costly modalities, such as multidetector computed tomography (MDCT), magnetic resonance tomography (MRT) or the combined use of positron emission tomography and computed tomography (PET/CT). Ultrasound offers the non-invasive display of organs without usage of ionizing radiation and it is widely available. However, colour-coded ultrasound and power Doppler do not allow the detection of tumor microcirculation. The introduction of contrast-enhanced ultrasound (CEUS) as well as new high-frequency ultrasound probes made it possible to detect and quantify tumor microcirculation with high resolution. CEUS has been used clinically on human beings for more than 10 years. During the last years different tumor models in experimental animals were used for the establishment of this new technique, e.g. in rats, hamsters and mice. CEUS allows the detection of functional parameters, such as the angiogenetic metabolic status of tissue pretreatment and posttreatment. Further research is required to solve the problems of absolute quantification of these perfusion parameters to allow the comparison of CEUS with other modalities (e.g. MRT and CT).

[Management of salivary gland diseases with contrast-enhanced ultrasound]. / Management von Speichel-drüsenerkrankungen mittels Kontrastmittelapplikation.

Obstructive diseases of the salivary glands are a common problem in otorhinolaryngology. They are mostly due to sialolithiasis followed by duct stenosis and other rarer causes. Several diagnostic modalities exist which allow classification of the disease; however, in 5-10% of all cases ultrasound and conventional radiological imaging do not provide a clear diagnosis. Ultrasound examination with contrast material injected into the duct (IA-CEUS, intraductal administered contrast-enhanced ultrasound) enables improved evaluation of obstructive diseases of the salivary glands and at the same time an evaluation of the parenchyma of the glands is possible. As a complementary method to conventional investigation techniques IA-CEUS is an economic and rapid method with low side-effects which improves the diagnostic assessment of ultrasound and results in a better treatment for patients.

[Sonographic analyses of obstructive diseases of the salivary gland using intraductal applications of contrast agent]. / Sonografische Analyse von obstruktiven Speicheldrüsenerkrankungen mittels intraduktaler Kontrastmittelapplikation.

Obstructive diseases of the salivary glands are a common problem of the salivary glands; often based on Sialolithiasis, duct stenosis, or other rarer reasons. There exist several diagnostic features to classify the disease; however, ultrasound or conventional radiological imaging does not provide a diagnosis in 5-10% of all cases. The intraductal applied contrast-enhanced ultrasound (IA-CEUS) improves the visualization of obstructive diseases of the salivary glands; simultaneously an evaluation of the parenchyma of the glands is possible. We think IA-CEUS is a promising tool, which improved the diagnostic assessment capabilities of ultrasound and results in a better treatment for patients with obstructive salivary gland diseases.

Imaging of carotid arterial diseases with contrast-enhanced ultrasound (CEUS).

Carotid duplex ultrasound is the standard of care for the initial diagnosis of carotid artery bifurcation diseases. But in difficult examinations, carotid abnormalities are commonly encountered and may represent a diagnostic challenge in patients with clinical symptoms as well as in the follow up after carotid endarterectomy or carotid artery stenting. Contrast enhanced ultrasound (CEUS) with low mechanical index (low MI) is a promising new method in the diagnosis and follow up of pathological carotid diseases. Unlike most contrast agents used for magnetic resonance imaging or computed tomography, the microbubbles used in CEUS with SonoVue(®) remain within the vascular space and hence can be used to study vascular disease. In addition to improving current carotid structural scans, CEUS has potential to improve or add extra information on carotid arterial diseases. This review describes the current carotid duplex ultrasound examination and compares the pathological findings with CEUS.

Non-invasive contrast enhanced ultrasound for quantitative assessment of tumor microcirculation. Contrast mixed mode examination vs. only contrast enhanced ultrasound examination.

PURPOSE: To evaluate the different ultrasound techniques for quantification of contrast enhanced ultrasound (CEUS) in an experimental rat prostate carcinoma model. METHOD AND MATERIALS: Prostate carcinoma (MLLB-2) cells were subcutaneously injected into the right flank of male rat (Charles River, Sulzfeld, Germany, 180 to 220 g body weight). Following 18 days of subcutaneous tumor growth 9 rats underwent CEUS examination. Real time CEUS was performed after a bolus injection of SonoVue (0.2 ml, Bracco, Italy) via the lateral tail vein using a high end ultrasound system (Siemens Sequoia 512®/Acuson, Mountain View) with an 15 Mhz probe. Two different CEUS techniques, pure contrast (pc) and contrast with background (cbg) examination, were analyzed (CPS-software). Exported signal intensity (SI)-time curves and the normalized area under the curve (AUC) for the active tumor tissue, whole tumor and necrosis were compared. RESULTS: The mean normalized AUC for the active tumor tissue and the whole tumor was 0.84 and 0.5 in the pure contrast examination group and 0.49 and 0.3 for the contrast examination with background signal. Therefore the signal intensity of the pc group was in every examination significant higher than of the cbg group (p < 0.02). The advantage of using the additional background information is to detect the anatomic landmarks in the solid tumor model in comparison to the pure contrast enhanced ultrasound examination. CONCLUSION: The complete extension of the tumor is much easier to detect with the cbg technique due to orientation of the anatomic landmarks. As the signal intensity of the pc group is always significant higher we recommend this technique for quantification of contrast enhanced ultrasound, especially for the follow up of tumor microcirculation.

Intraductally applied contrast-enhanced ultrasound (IA-CEUS) for improved visualization of obstructive diseases of the salivary glands, primary results.

PURPOSE: Obstructive diseases of the salivary glands are often based on Sialolithiasis; however, conventional radiological imaging or ultrasound does not provide a diagnosis in 5-10% of all cases. It was the aim of our study to examine the effectiveness and viability of an intraductal applied contrast-enhanced ultrasound (IA-CEUS) to improve the visualization of obstructive diseases of the salivary glands in comparison to conventional ultrasound and clinical symptoms. MATERIALS AND METHODS: The study included fifteen patients with swelling of indeterminate cause and/or pain of one or more salivary glands. A high-end ultrasound machine (Siemens, ACUSON, S 2000, Germany) with a multi-frequency linear 9 MHz transducer was used to carry out contrast-enhanced ultrasound with SonoVue. RESULTS: All patients were examined using all diagnostic ultrasound tools of the study. The results show that the procedure is easy and convenient to perform, as well as efficient, but more significantly, that the intraductal contrast agent improved the diagnostic assessment capabilities of ultrasound for patients with obstructive salivary gland diseases, thereby helping to identify the best treatment. CONCLUSION: In comparison to conventional ultrasound, the use of an intraductal applied contract-enhanced ultrasound not only improved the visualization of the glandular duct system as a whole, but was less time-consuming as well as more reproducible. Thus, IA-CEUS with an intraductal applied contrast agent (IA-CEUS) is a promising tool that provides additional helpful information and an improvement for cases involving patients with unclear symptoms.

[Secondary high-malignant transformation of a low-malignant epithelial-myoepithelial carcinoma]. / Sekundäre hochmaligne Transformation eines niedrigmalignen epithelial-myoepithelialen Karzinoms.

The rare entity of epithelial-myoepithelial carcinoma (EMC) belongs to a group of tumors with a biphasic ductular growth pattern, mostly with a dominating myoepithelial component and low-grade malignancy. We report on the rare constellation of a primary low-malignant EMC with high malignant transformation (so-called dedifferentiation) into a highly malignant myoepithelial carcinoma. In the eight published cases so far, the high-malignant component was reported to be either adenocarcinoma or undifferentiated carcinoma or was otherwise not specified. To the best of our knowledge, this is the first case report of a high-grade myoepithelial carcinoma transforming from a low-grade EMC. We discuss interesting parallels to the pathogenesis of secondary transformation of carcinoma ex pleomorphic adenoma.

[Pleomorphic adenoma: pitfalls and clinicopathological forms of progression]. / Das pleomorphe Adenom: Pitfalls in der Diagnostik und klinisch-pathologische Progressionsformen.

In the majority of cases the diagnosis of pleomorphic adenoma (PA) is straightforward. In "monomorphic" types of PA problems may result: Epithelial-rich PA need to be distinguished from basal cell adenoma or canalicular adenoma. PA dominated by mesenchymal, spindle-shaped differentiation need to be distinguished from myoepithelioma or soft tissue tumours like schwannoma. Focal biphasic-tubular differentiation with CK7/18-positive ductal cells is good evidence for a tumour within the wide spectrum of PA. Focal peripheral pseudoinfiltration can represent physiological growth pattern of PA; this may render a difficult distinction from low-malignant carcinomas like adenoid-cystic or epithelial-myoepithelial carcinoma, harbouring also tubular structures. The different progression steps of carcinoma ex pleomorphic adenoma (CEPA), starting with intraductal carcinoma, are highly relevant with respect to prognosis and therapy. Early stages including CEPA with minor extracapsular invasion show favourable prognosis, while cases with extensive extracapsular invasion carry a dismal prognosis.