Comparison of embolic effect between water-in-oil emulsion and microspheres in transarterial embolization for rat hepatocellular carcinoma model.

AIM: To compare two different embolic materials, water-in-oil (W/O) emulsion followed by gelatin particles and microspheres in transarterial embolization (TAE), using a rat hepatocellular carcinoma model. METHODS: Twenty rats bearing N1S1 cells were divided into the W/O emulsion group and Microsphere group. Water-in-oil emulsion was created by a glass membrane emulsification device. The tumor vascularity was measured by contrast-enhanced ultrasonography 24 h before and 10 min and 48 h after TAE. Tumor necrosis, hepatic infarction ratio surrounding the tumor, and locations of the embolic materials 48 h after TAE were assessed. The changes of serum liver enzymes were also evaluated. Statistical significance was determined by using either the Mann-Whitney U-test or Fisher's exact test. RESULTS: The tumor vascularity 48 h after TAE was significantly higher in the Microsphere group (20.1 vs. 3.76%, P = 0.016). The overflow of Lipiodol into the portal veins surrounding the tumor was seen, whereas microspheres were seen only in the artery. The percentage of necrotic area and complete response ratio in the W/O emulsion group was significantly higher (99.9 vs. 87.6%, P = 0.029 and 87.5 vs. 28.6%, P = 0.041, respectively). Serum aspartate aminotransferase and serum alanine aminotransferase levels 48 h after TAE were significantly higher in the W/O emulsion group (P < 0.01). CONCLUSIONS: The embolization using W/O emulsion followed by gelatin particles showed stronger antitumor effects with the occlusion of both the tumor feeding artery and the portal vein compared with microspheres, which occluded only the arteries.

[Preoperative Detection of Pleural Adhesions Using Transthoracic Ultrasonography].

Recently, there has been an increase in the experience of lung surgery in cases with a history of thoracotomy or pneumonia. In these cases, pleural adhesion is often seen and makes the surgery to be difficult. Especially in thoracoscopic surgery, lung damage must be care at the 1st port insertion. In this report, the usefulness of the extent of pleural adhesion to the chest wall before surgery by using a transthoracic ultrasonography was assessed. Between April 2017 and September 2018, 32 patients underwent preoperative ultrasound examination, and 128 ports were evaluated whether had adhesions or not using lung sliding sign. All patients of 128, 24 adhesions were found at surgery, resulting in 14 true positive, 10 false negative, 0 false positive, and 104 true negative findings [sensitivity:58.3% (14/24), specificity: 100.0% (104/104), accuracy:92.2% (118/128)]. Especially, about the 1st port, accuracy was 93.8 % (30/32). In Conclusion, preoperative transthoracic ultrasonography could provide useful information on the pleural adhesion leading safe initial thoracoscopic access without lung injury.

Efficacy of sonazoid (perflubutane) for contrast-enhanced ultrasound in the differentiation of focal breast lesions: phase 3 multicenter clinical trial.

OBJECTIVE: The objective of our study was to compare the efficacy of contrast-enhanced ultrasound (CEUS) using the ultrasound contrast agent Sonazoid (perflubutane) with unenhanced ultrasound and supplementary contrast-enhanced MRI in the differential diagnosis (benign vs malignant) of focal breast lesions. The safety of Sonazoid was also assessed in this study. SUBJECTS AND METHODS: A total of 127 patients with focal breast lesions were enrolled in this study at five centers in Japan. Three reviewers who were blinded to the patient characteristics independently assessed the ultrasound images and MR images in a randomized sequence. The accuracy, sensitivity, and specificity of CEUS, unenhanced ultrasound, and supplementary contrast-enhanced MRI for the differential diagnosis were compared using generalized estimating equation analyses. Diagnostic confidence was also assessed. RESULTS: The accuracy of CEUS was significantly higher than that of unenhanced ultrasound (87.2% vs 65.5%, respectively; p < 0.001). In addition, CEUS showed significantly higher specificity, although the improvement in sensitivity was not statistically significant. The accuracy and specificity were significantly higher with CEUS than with contrast-enhanced MRI, but the improvement in sensitivity was not statistically significant. The area under the curve in a receiver operating characteristic analysis was significantly greater with CEUS than with unenhanced ultrasound. The incidence of adverse events was 11.4% and the incidence of adverse drug reactions was 3.3%. All adverse drug reactions were mild. CONCLUSION: CEUS using Sonazoid was confirmed to be superior to unenhanced ultrasound for the differential diagnosis (benign vs malignant) of focal breast lesions in terms of diagnostic accuracy with no serious adverse reactions.

Ultrasonographic findings in nevus lipomatosus cutaneous superficialis: What differentiates this tumor from other soft tissue tumors?

Nevus lipomatosus cutaneous superficialis is a rare, benign hamartoma characterized by mature adipocyte proliferation in the dermis. It is frequently difficult to distinguish clinically from soft tissue tumors, including lipoma, neurofibroma, venous malformation, and angiolipoma. Notably, the classical form, which shows multiple and sometimes enlarged nodules, is difficult to differentiate from liposarcoma based on clinical examination, computed tomography, and magnetic resonance imaging findings. Therefore, to ascertain the utility of ultrasonography in diagnosing nevus lipomatosus cutaneous superficialis, sonographic examinations were performed on eight patients with nevus lipomatosus cutaneous superficialis. All patients had ill-defined hyperechoic masses in the dermis or from the dermis to the subcutis, and the posterior echoes were attenuated in seven patients. Color Doppler sonography revealed no blood flow to the lesions. Ultrasound images were created using the reflections of ultrasound waves at interfaces with different acoustic impedances. Therefore, it is assumed that, in nevus lipomatosus cutaneous superficialis, the ultrasound beam is scattered by ectopic mature adipocytes intermingled with collagen bundles, which are shown as hyperechoic masses. Furthermore, the scattering of the ultrasound beam is thought to reduce tissue penetration, which may attenuate the posterior echo.

Transcranial contrast-enhanced ultrasonography with Sonazoid in semiquantitative evaluation of brain perfusion.

PURPOSE: To semiquantitatively evaluate brain perfusion by transcranial contrast-enhanced ultrasonography (TCEUS) using Sonazoid. METHODS: We performed TCEUS in 11 healthy volunteers and seven patients with occlusive cerebrovascular disease involving the anterior circulation. After recording first-pass perfusion images on one side of the head and flush-replenishment (FR) images on both sides, we measured the time from arrival to peak (TAP) and peak intensity (PI) at first pass. Using the FR method, plateau value (A) and rise rate (ß) of intensity (I) were obtained from the curve I(t) = A(1 - e (-ß*t) ). RESULTS: In the patients, TAP was longer and PI was smaller in middle cerebral artery (MCA) areas than in posterior cerebral artery (PCA) areas on the ipsilesional side of the head (p < 0.05). A and ß were smaller in MCA areas than in PCA areas on the ipsilesional side of the head (p < 0.05), while these parameters showed no apparent differences between MCA and PCA areas in the volunteers. CONCLUSION: TCEUS with Sonazoid allows effective semiquantitative evaluation of brain perfusion.

Phase II clinical study of DD-723 (perflubutane): dose-response study in patients with breast tumors.

PURPOSE: We compared the contrast effect of three doses of DD-723 in subjects with breast tumors to determine the recommended dose. We then evaluated differential diagnosis results using plain ultrasonography, contrast-enhanced ultrasonography (plain + enhanced), and contrast-enhanced magnetic resonance imaging (MRI) compared to the pathological diagnosis. METHODS: To evaluate the contrast effect, contrast-enhanced ultrasonic images were independently evaluated in a randomized sequence by three blinded reviewers trained in the evaluation method beforehand. Multiple evaluation results from the three reviewers were used to assess the overall contrast effect. The differential diagnosis was evaluated independently by three blinded reviewers using contrast-enhanced ultrasonic images and contrast-enhanced magnetic resonance images in a randomized sequence; reviewers were also blinded to subject characteristics. Multiple evaluation results from the three reviewers were used to assess the overall differential diagnosis. RESULTS: The recommended dose of DD-723 is an intermediate dose of 0.12 µL MB/kg. Accuracy, sensitivity, and specificity were improved more in the differential diagnosis by contrast-enhanced ultrasonography than in plain ultrasonography. Accuracy and specificity were better and sensitivity similar compared to contrast-enhanced MRI. CONCLUSIONS: An intermediate dose showed the highest efficacy in terms of overall contrast effect. Contrast-enhanced ultrasonography is safe and useful when used in differential diagnosis.

Artificial intelligence (AI) models for the ultrasonographic diagnosis of liver tumors and comparison of diagnostic accuracies between AI and human experts.

BACKGROUND: Ultrasonography (US) is widely used for the diagnosis of liver tumors. However, the accuracy of the diagnosis largely depends on the visual perception of humans. Hence, we aimed to construct artificial intelligence (AI) models for the diagnosis of liver tumors in US. METHODS: We constructed three AI models based on still B-mode images: model-1 using 24,675 images, model-2 using 57,145 images, and model-3 using 70,950 images. A convolutional neural network was used to train the US images. The four-class liver tumor discrimination by AI, namely, cysts, hemangiomas, hepatocellular carcinoma, and metastatic tumors, was examined. The accuracy of the AI diagnosis was evaluated using tenfold cross-validation. The diagnostic performances of the AI models and human experts were also compared using an independent test cohort of video images. RESULTS: The diagnostic accuracies of model-1, model-2, and model-3 in the four tumor types are 86.8%, 91.0%, and 91.1%, whereas those for malignant tumor are 91.3%, 94.3%, and 94.3%, respectively. In the independent comparison of the AIs and physicians, the percentages of correct diagnoses (accuracies) by the AIs are 80.0%, 81.8%, and 89.1% in model-1, model-2, and model-3, respectively. Meanwhile, the median percentages of correct diagnoses are 67.3% (range 63.6%-69.1%) and 47.3% (45.5%-47.3%) by human experts and non-experts, respectively. CONCLUSION: The performance of the AI models surpassed that of human experts in the four-class discrimination and benign and malignant discrimination of liver tumors. Thus, the AI models can help prevent human errors in US diagnosis.

A case of perforated multiple gastric duplication cysts with five-layered appearance on ultrasonography.

A case of perforated multiple gastric duplication cysts is presented. One of the gastric duplication cysts without perforation was seen on ultrasonography (US) with the following specific findings of gastric duplication cysts: a five-layered appearance, fold-like structures in the wall, and blood supply from the gastroepiploic artery. Other cysts with perforation presented with irregular and thin walls with a lack of the "double-wall sign" on US. These characteristic findings may be specific to perforated multiple gastric duplication cysts.

Secondary aortoduodenal fistula identified by ultrasonography.

A 73-year-old man underwent coronary artery bypass grafting, abdominal aortic aneurysm resection, and prosthetic implantation as a single procedure in 2002. His progress was favorable until April 2008, when he was admitted to our hospital with melena. B-mode ultrasonography revealed a 5-mm defect in the abdominal aorta at the graft anastomosis, and an umbilicated lesion was seen projecting between the posterior wall of the third part of the duodenum and the abdominal aorta. A color signal was noticed at this site on color Doppler ultrasonography, leading to the diagnosis of a secondary aortoduodenal fistula (ADF). We resected the inflammatory mass comprising the graft and the third part of the duodenum, and performed prosthetic re-implantation, omentopexy, and duodenojejunostomy. We could not find any previous reports of successful identification of secondary ADF using ultrasonography. When a patient with gastrointestinal hemorrhage following reconstructive aortic surgery is encountered in the emergency department, ultrasonography may be considered to be a useful modality in the diagnosis of secondary ADF.

Useful Parameters in Dynamic Contrast-enhanced Ultrasonography for Identifying Early Response to Chemotherapy in a Rat Liver Tumor Model.

OBJECTIVES: The objective of the study is to determine a parameter on the time-intensity curve (TIC) of dynamic contrast-enhanced ultrasonography (DCE-US) that best correlates with tumor growth and to evaluate whether the parameter could correlate with the early response to irinotecan in a rat liver tumor model. MATERIAL AND METHODS: Twenty rats with tumors were evaluated (control: Saline, n = 6; treatment: Irinotecan, n = 14) regarding four parameters from TIC: Peak intensity (PI), k value, slope (PI × k), and time to peak (TTP). Relative changes in maximum tumor diameter between day 0 and 10, and parameters in the first 3 days were evaluated. The Mann-Whitney U-test was used to compare differences in tumor size and other parameters. Pearson's correlation coefficients (r) between tumor size and parameters in the control group were calculated. In the treatment group, relative changes of parameters in the first 3 days were compared between responder and non-responder (<20% and ≥20% increase in size on day 10, respectively). RESULTS: PI, k value, PI × k, and TTP significantly correlated with tumor growth (r = 0.513, 0.911, 0.665, and 0.741, respectively). The mean RC in k value among responders (n = 6) was significantly lower than non-responders (n = 8) (mean k value, 4.96 vs. 72.5; P = 0.003). CONCLUSION: Parameters of DCE-US could be a useful parameter for identifying early response to irinotecan.

Ultrasonic Heating Detects Lipiodol Deposition within Liver Tumors after Transarterial Embolization: An In Vivo Approach.

Computed tomography (CT) is the standard method to evaluate Lipiodol deposition after transarterial embolization (TAE) for a long period. However, iodine but not Lipiodol can be observed on CT. A minimally invasive other method to detect Lipiodol has been needed to evaluate accurate evaluation after procedure. The purpose of this study was to evaluate the efficacy of using the rate of change in sound velocity caused by ultrasonic heating to reflect Lipiodol accumulation after TAE in a rat liver tumor model. We analyzed the association of this developed technique with CT images and histological findings. Eight rats bearing N1S1 cells were prepared. After confirmation of tumor development in a rat liver, Lipiodol was injected via the hepatic artery. Seven days after TAE, CT scan and sound velocity changes caused by ultrasonic heating were measured, and then the rats were sacrificed. An ultrasonic pulse-echo method was used to measure the sound velocity. The temperature coefficient of the sound velocity in each treated tumor was evaluated and compared with the mean CT value and the histological Lipiodol accumulation ratio. Pearson's correlation coefficients were calculated to assess the correlation between the measured values. The correlation coefficient (r) of the mean CT value and histological Lipiodol accumulation ratio was 0.835 (p = 0.010), which was considered statistically significant. Also, those of the temperature coefficient of the sound velocity and the histological Lipiodol accumulation ratio were statistically significant (r = 0.804; p = 0.016). To our knowledge, this is the first study that reported the efficacy of ultrasonic heating to detect Lipiodol accumulation in rat liver tumors after TAE. Our results suggest that the rate of change in sound velocity caused by ultrasonic heating can be used to evaluate Lipiodol accumulation in liver tumors after TAE, and thus could represent an alternative to CT in this application. This new innovative technique is easy to treat and less invasive in terms of avoiding radiation compared with CT.

Comparing the extent of breast cancer tumors through contrast-enhanced ultrasound vs B-mode, opposed with pathology: evergreen study.

BACKGROUND: To prove the efficacy of contrast-enhanced ultrasound (CEUS) in determining the extent of resection, more evidence about B-mode and CEUS as opposed to pathology is required. We compared maximum tumor width measured on B-mode/CEUS images with that determined pathologically. METHODS: In this retrospective multicenter study, 152 operable breast cancer patients who had undergone both B-mode and CEUS were analyzed. Maximum tumor width on B-mode and CEUS, and on the postoperative pathological examination (P), was measured by the participating investigators. In addition, maximum width was assessed in B-mode and CEUS image sets by independent reviewers blinded to all patient information. We analyzed differences in maximum width between CEUS, B-mode and P. RESULTS: The mean widths as measured by the participating investigators were 15 ± 7 mm (B-mode), 19 ± 8 mm (CEUS), and 17 ± 9 mm (P). The difference subtracted P from B-mode was - 3 ± 7 mm (p < 0.0001), and that from CEUS was 1 ± 6 mm (p = 0.0163). The mean widths as measured by the independent reviewers were 16 ± 7 mm (B-mode) and 18 ± 7 mm (CEUS). The difference subtracted P from B-mode was - 2 ± 8 mm (p = 0.0114), while that from CEUS was 1 ± 7 mm (p = 0.1921). CONCLUSIONS: Maximum lesion width measurement showed a tendency to increase in the order of B-mode, to P and CEUS. The difference in measurement between P and B-mode was significant, but there was no significant between CEUS and P. These results provide additional information of tendency patterns in measuring the maximum lesion width through enhancement on CEUS.

Evaluation of background parenchymal enhancement in breast contrast-enhanced ultrasound with Sonazoid®.

PURPOSE: The objective of this study was to retrospectively evaluate the association between background parenchymal enhancement (BPE) on contrast-enhanced ultrasound (CEUS) with Sonazoid® and patient characteristics. Additionally, background parenchymal tissues with the high-contrast effect were pathologically observed compared to those showing the low-contrast effect. METHODS: A total of 65 patients who underwent breast CEUS with Sonazoid® between January 2010 and November 2013 were enrolled. Regions of interest (ROIs) were put on the tumor and on the background parenchymal tissue. The dB values during the nonenhanced time and at peak contrast enhancement were measured based on the time intensity curve (TIC) drawn by the ROI. The differences in the dB values of pre- and post-enhanced time were obtained separately for ROIs on the tumor and ROIs on the parenchymal tissue. The patient characteristics studied were age, menstrual status, mammographic density, BPE on magnetic resonance imaging (MRI), and pathological diagnoses of breast tumors. RESULTS: There was a weak negative correlation between BPE on CEUS and age. As for the contrast effect of parenchymal tissue, there was a significant difference between the menstruating and menopausal groups. There was no significant difference among the levels of mammographic density, and among the degrees of contrast effect on MRI. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status. The parenchymal tissue with the low-contrast effect showed pathological atrophy. CONCLUSION: The degree of BPE on CEUS appeared related to age, menstruating or menopausal, and atrophy of breast tissue. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status.

Uterine adenomatoid tumor associated with lymph node lesions: a case report.

We report a case of uterine adenomatoid tumor (AT) with regional lymph node involvement in a 49-year-old woman. Magnetic resonance imaging revealed an aggregated cystic mass in the posterior uterine wall with partial protrusion of the tumor outside the uterus, and cystic masses of same characteristics in the bilateral obturator and right common iliac lymph nodes. FDG PET/CT revealed no significant FDG uptake in the uterine and lymph node lesions. Taking possible lymph node metastasis into consideration, hysterectomy and lymph node biopsy were performed and it revealed AT of the uterus and the lymph nodes histopathologically.

Initial experience of transcranial contrast-enhanced ultrasonography with Sonazoid in the evaluation of microvascular brain anatomy.

PURPOSE: The aim of this study is to visualize the microvascular anatomy of the brain parenchyma using transcranial contrast-enhanced ultrasonography (TCEUS) with Sonazoid. METHODS: TCEUS was performed in 14 subjects using the transtemporal and transnuchal approach (two patients with cerebral infarction and 12 healthy volunteers). An ultrasound system equipped with a 2- to 4-MHz sector probe set to coded phase inversion mode with a mechanical index of 0.4 was used. An intravenous bolus of Sonazoid (0.01 ml/kg) was injected. First-pass perfusion images were recorded from injection to 50 s after injection, and flush-replenishment (FR) images were recorded three times on both sides of the head from 1 to 5 min after injection. RESULTS: Real-time perfusion images of the brain parenchyma could be observed in all cases. At first pass, the main cerebral arteries began to be visualized at 10-20 s after injection, followed by the microvasculature at 15-30 s. The microvasculature reconstructed by the FR method could be observed on both sides of the head. CONCLUSION: TCEUS with Sonazoid allows effective, noninvasive evaluation of brain parenchyma microvasculature.

Updates on Ultrasonography Imaging in Abdominal Aortic Aneurysm.

Abdominal aortic aneurysms (AAAs) are life-threatening and are associated with >80% mortality when they rupture. Therefore, detecting these aneurysms before they rupture is critical. Ultrasonography is a non-invasive tool that is used for screening AAAs by measuring abdominal aorta diameter. A recent meta-analysis demonstrated the positive effects of ultrasonography. To date, aneurysm diameter is the most reliable predictor for aneurysm rupture and is used as a criterion for surgical intervention. However, some AAAs rupture at small diameters. Therefore, a better predictor for AAA rupture that is independent of aneurysm diameter is needed. Recently, an aortic wall strain examined using ultrasonography has been reported to have a potential in predicting AAA rupture. Since the introduction of endovascular aneurysm repair (EVAR), a paradigm shift has occurred in the management of AAAs. EVAR is broadly spread with the advantage of early favorable results but with concerning endoleak complications. At present, computed tomography angiography (CTA) is considered to be a gold standard for surveillance following EVAR, but it encounters some problems, such as contrast usage or radiation exposure. Ultrasonography offers an examination free from these problems and can this be an alternative to CTA. In this review article, current trends and new technologies regarding AAA assessment using ultrasonography are introduced.

Preoperative Detection of Pleural Adhesions Using Ultrasonography for Ipsilateral Secondary Thoracic Surgery Patients.

BACKGROUND/AIM: Video-assisted thoracic surgery (VATS) for ipsilateral reoperations is challenging because of the potential for pleural adhesions. Insertion of the initial port can lead to lung injury because of the blinded intrathoracic area. We assessed the usefulness of ultrasonography before VATS to reduce the incidence of lung injury at the time of the initial port insertion during secondary ipsilateral VATS. PATIENTS AND METHODS: Thirty-three patients who underwent repeat VATS for ipsilateral pulmonary lesions were included. All patients underwent preoperative ultrasonography to assess the possible presence of pleural adhesions using the lung sliding sign. RESULTS: Seven adhesions were found at the VATS ports. Two of these adhesions were not evaluated as pleural adhesions using ultrasonography; however, they were loose. All initial ports were inserted without lung injury. There were no major complications. CONCLUSION: Preoperative detection of pleural adhesions using ultrasonography can determine the best initial port for secondary ipsilateral VATS.

Ultrasonography for Detecting Adhesions: Aspirin Continuation for Lung Resection Patients.

BACKGROUND/AIM: Aspirin reduces cardiovascular disease and/or stroke risks. However, perioperative aspirin use remains controversial. We assessed the efficacy of ultrasonography to facilitate video-assisted thoracic surgery (VATS). We analyzed the perioperative management of patients using aspirin and its association with bleeding events during lung cancer surgery. PATIENTS AND METHODS: A total of 38 patients who underwent VATS after continuing or discontinuing aspirin were examined. Ultrasound was performed preoperatively to evaluate the pleural adhesions. Fisher's exact test was used to analyze correlations between the two groups. RESULTS: Dense adhesions were found at VATS ports using ultrasonography (accuracy: 100%). No differences were detected in bleeding, thrombotic events, or operative times between the aspirin and non-aspirin groups. There were differences in bleeding (p=0.009) and operative times (p=0.021) between the dense adhesion and non-dense adhesion groups. CONCLUSION: Preoperative detection of pleural adhesions using ultrasonography was useful in selecting pulmonary resection patients who continued aspirin perioperatively.

Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model.

AIM: To investigate Kupffer cell dynamics and phagocytic activity, using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet, followed by contrast enhanced ultrasonography (CEUS) using Levovist. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy. The status of the Kupffer cells was compared between the two groups, using the immunohistochemical staining technique. RESULTS: After 4 or more wk of the CDAA diet, CEUS examination revealed a decrease in the signal intensity, 20 min after intravenous Levovist. Fluorescent microscopic examination showed that the uptake of latex beads by the Kupffer cells was reduced at week 1 and 2 in the study group, compared with the controls, with no further reduction after 3 wk. Immunohistochemical staining revealed no significant difference in the Kupffer cell counts between the control group and the CDAA group. CONCLUSION: CEUS examination using Levovist demonstrated reduced contrast effect and phagocytic activity in the liver parenchymal phase, although the Kupffer cell numbers were unchanged, indicating reduced phagocytic function of the Kupffer cells in the rat NASH model. We believe that CEUS examination using Levovist is a useful screening modality, which can detect NASH in fatty liver patients.