Toshiko Hirai

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.

A familial case of visceral toxocariasis due to consumption of raw bovine liver

We present 3 adult cases of visceral toxocariasis from the same family, who each consumed thin slices of raw bovine liver weekly, and developed eosinophilia and multiple small lesions in their livers and lungs. Serological examinations using the larval excretory-secretory product of Toxocara canis strongly indicated infection with Toxocara species larvae. The patients responded well to treatment with albendazole. Ingestion of raw liver from paratenic animals is considered to be a common transmission route of human toxocariasis, especially in adults.

Usefulness of color Doppler flow imaging in differential diagnosis of multilocular cystic lesions of the kidney.

Color Doppler flow imaging was carried out in 10 multilocular cystic lesions of the kidney. These consisted of three renal cell carcinomas, three hemorrhagic renal cysts, one benign multilocular cystic nephroma, two infected renal cysts, and one benign multilocular renal cyst secondary to von Hippel‐Lindau disease. In the patients with renal cell carcinoma, color signals were obtained at the septum and in the solid component within the lesions. A pulsatile wave with a large maximum flow velocity and a high PI value was obtained in two of them. In one of the patients with hemorrhagic renal cysts, color signals were obtained at the region of the septum. In the other benign lesions, however, color signals were obtained only at the peripheral margin, and the flow waveform in these cases was identical to the waveforms found in the interlobar arteries. This study suggested that color display in the lesion well reflects its vascularity in patients with multilocular cystic renal diseases and that measurement of the systolic maximum flow velocity by fast Fourier transform analysis is useful for the differential diagnosis of malignant versus benign lesions.

Color doppler flow imaging of pancreatic arteriovenous malformation

Pancreatic AVM is a rare entity and to our knowledge, only 17 cases have been described in the radi· ologic literature.l-13 Given the nature of this disease, color Doppler flow imaging may be very valuable in the diagnosis, but none of the earlier reported cases had been evaluated by this imaging technique. This report describes characteristic color Doppler findings that are useful in the diagnosis of pancreatic AVM.

Criteria for ultrasound diagnosis of deep venous thrombosis of lower extremities

When testing the pelvic region, a 3.5-MHz convex probe or sector probe is primarily used. For testing the femoral, popliteal, and crural areas, a 7to 10-MHz linear probe or a 3.5to 5.0-MHz convex probe is primarily used. B-mode ultrasonography is adopted for morphological diagnosis. Color Doppler or pulse Doppler methods are employed for evaluation of blood fl ow. With the color Doppler method, the velocity scale is set low to 10–20 cm/s. Objectives

Qualitative Diagnosis of Hepatocellular Carcinoma by Contrast Enhanced Ultrasonography Using Coded Harmonic Angio with Levovist

We attempted to evaluate diagnosis and characterization and to access therapeutic effects in cases of hepatocellular carcinoma (HCC) by contrast enhanced ultrasound (CEUS) using Coded Harmonic Angio (CHA) with Levovist, an intravenous ultrasound contrast agent. Fifty-seven HCC foci in 39 patients, including 37 HCC foci in 28 patients before and after transcatheter arterial chemoembolization or radio frequency ablation, were examined by CEUS using the CHA mode, which is under development. This mode uses digitally encoded pulse sequences that identify and suppress nonmoving tissue signals and enhance contrast signals from Levovist in a gray-scale format. In all cases, abundant tortuous intratumoral blood flow was visualized in the early vascular phase by continuous transmission, while tumor stain was recognized by consecutive 1-to-2 second intermittent transmission. Residual tumor area after treatment was also clearly depicted by intratumoral blood flow and partial enhancement. CEUS using CHA with Levovist is likely to become important in the qualitative diagnosis of hepatic tumor and to improve the efficacy of treatment for HCC.

Adventitial cystic disease of the popliteal artery demonstrated by intravascular ultrasonography.

Until recently, ACD of the popliteal artery was diagnosed predominantly by angiography. MR imaging and ultrasonography imaging now are used more frequently because they are less invasive and provide more information than angiography. Recently, IVUS is currently the standard of reference for imaging vessel wall morphology. We report a case of ACD of the popliteal artery in which IVUS shows the relationship between cysts and vascular wall as the pathologic feature. CASE REPORT

Contrast-enhanced ultrasonography with Sonazoid for evaluation of renal microcirculation

PurposeThe renal medullary microcirculation plays an important role in regulating sodium and water excretion, and its impairment is closely associated with various renal diseases. Contrast-enhanced ultrasonography (CEUS) using Sonazoid has not yet been reported as a method for evaluating the renal microcirculation; consequently, this study was carried out to reveal the characteristics of renal microcirculation using CEUS with Sonazoid.MethodsCEUS was performed on three healthy volunteers after they had fasted for at least 6 h. A GE LOGIQ7 ultrasound unit was used with a 2.0- to 5.5-MHz convex probe. Within approximately 1 min of intravenous injection of 0.0050 ml/kg Sonazoid, contrast images of the right kidney were acquired using a coded phase-inversion mode. Time-intensity curves were calculated for the cortex and medulla.ResultsPeak contrast intensity was significantly higher in the cortex (−56.4 ± 1.9 dB) than in the medulla (−66.7 ± 1.7 dB; P < 0.005). Peak times were significantly earlier in the cortex (17.4 ± 3.7 ms) than in the medulla (28.8 ± 6.3 ms; P < 0.05).ConclusionCEUS using Sonazoid enables differentiation between the cortical and medullary microcirculation and is useful in clarifying renal pathophysiology and pharmacology.

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.

Expectations for contrast-enhanced ultrasonography

Sonazoid, the only ultrasound contrast medium that can be used clinically in Japan at present, has been covered by insurance for focal liver lesions since 2007 and for focal breast lesions since 2012. In addition to serving as a blood pool agent, Sonazoid which is phagocytized by Kupffer cells, enhances normal liver parenchyma in the post vascular phase. Therefore, Sonazoid was first used for the purpose of detection and qualitative diagnosis of focal liver lesions in cases in which qualitative diagnosis with other diagnostic imaging was difficult and cases in which contrast-enhanced CT and MRI were contraindicated due to renal dysfunction or allergy to contrast agents, etc. Over 300,000 examinations have been performed with Sonazoid in the 6 years since 2007. Recently, accurate and appropriate treatment of hepatic tumors that are difficult to detect on B-mode ultrasound has been made possible by clearly depicting hepatic tumors with contrast-enhanced ultrasound. Also, during surgery, lesions that are unclear on B-mode ultrasound can be better detected and the extent of the lesion can be more clearly depicted as a result of enhancement. Contrast-enhanced ultrasound is now an indispensable examination for supporting the treatment of hepatic carcinoma and assessment of the response to treatment, in addition to its use for intraoperative ultrasound; it cannot be replaced by other modalities. Contrast-enhanced ultrasound with Sonazoid for focal breast lesions is now covered by insurance after being recognized as superior to B-mode ultrasound and contrastenhanced MRI for differentiating between malignant and benign breast tumors. It has been 14 months since coverage was authorized, but its use for this purpose is not yet widespread. One possible reason for this is that the clinical usefulness of this method, other than differentiating malignant from benign breast lesions, is not yet clear. In the case of breast lesions that can be depicted on B-mode ultrasound, pathological diagnosis can be made easily by fine needle aspiration cytology or core needle biopsy under ultrasound guidance; therefore, there is very little dependence on contrast-enhanced ultrasound for the differential diagnosis of malignancy. In addition, institutions that perform breast ultrasound do not always have the equipment to perform contrast-enhanced ultrasound. Moreover, most breast ultrasound examinations are performed by sonographers alone; securing a doctor to inject the contrast agent is another obstacle to its widespread use. In the area of breast imaging, it is hoped that contrastenhanced ultrasound will be useful for diagnosing the spread of breast cancer, assessing the response to chemotherapy, and diagnosing postoperative recurrence, etc., for which we currently rely on contrast-enhanced MRI. Unlike with contrast-enhanced MRI, which is performed with the patient in the prone position, if the spread of a lesion can be diagnosed with contrast-enhanced ultrasound, which can be performed with the patient in the operative position, it is possible to accurately mark the involved area and resect just the right amount of lesion. Also, unlike contrast agents for CT and MRI, which diffuse into the interstitial space, ultrasound contrast agents, which are microbubbles, probably yield images that accurately reflect tumor blood perfusion; therefore, it may also be useful to assess response to chemotherapy and differentiate between postoperative scars and recurrent lesions. In order for use of contrast-enhanced ultrasound to become more widespread for imaging areas other than the T. Hirai (&) Department of Endoscopy and Ultrasound, Nara Medical University, Nara, Japan e-mail: thirai@naramed-u.ac.jp