Detection of hepatic metastases with low MI real time contrast enhanced sonography and SonoVue.

AIM: SonoVue is the first ultrasound contrast agent which allows repeated continuous examination of the liver in real time. The aim of this study was to compare low mechanical index (MI) real time contrast enhanced ultrasound of the liver, using the contrast agent SonoVue, with conventional B-mode sonography for the detection of hepatic metastases. METHOD: 40 patients with known malignancy and at least one liver lesion on conventional B-mode sonography were included. Conventional B-mode sonography was performed followed by contrast enhanced ultrasound (CEUS) of the liver in the arterial (< 30 sec), portal-venous (40-120 sec) and delayed phase (> 120 sec) after injection of SonoVue. CEUS was performed using contrast specific imaging and low MI (< 0.3). Number, location and size of metastases on baseline and CEUS were compared with CT or MRI (blinded reader). RESULTS: 37 patients had 128 metastases on CT or MRI. Baseline US showed 74 metastases confirmed by reference examination (69%), while CEUS yielded 109 metastases (sensitivity 90%) (p < 0.001). On CEUS, 35 additional metastases not seen on baseline but confirmed by reference imaging were detected in 14 patients (36%). In 8 patients, CEUS showed 13 metastases not seen on reference imaging. CONCLUSION: Detection of hepatic metastases is substantially improved by low MI real time contrast enhanced ultrasound with SonoVue compared to conventional B-mode sonography.

Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents.

Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet.

Case study: chronic erysipelas of the sow--a subclinical manifestation of reproductive problems.

Systemic infections with Erysipelothrix rhusiopathiae are usually associated with skin lesions, vegetative endocarditis and arthritis, but they can also cause reproductive symptoms such as abortion, increased stillbirths, and smaller litter size. In a large Hungarian breeding unit that had ceased to vaccinate the sows against erysipelas, an increased incidence of pre- and post-partal vulval discharge, increased weaning-to-oestrus intervals, decreased farrowing rates, and reductions in total number of pigets born and live-born litter size were reported. Anterior vaginal swabs were obtained from 64 sows shortly before parturition and they all yielded heavy growths of E. rhusiopathiae. A vaccination programme with a killed vaccine was reinstated and subsequently the incidence of vulval discharge and weaning-to-oestrus intervals were decreased and total born and live-born litter size were increased. In the absence of a control group definitive conclusions can not be made regarding the effect of vaccination against E. rhusiopathiae on sow fertility. However, it is not unreasonable to suggest that the aetiology of the reduced sow fertility in the present herd did involve E. rhusiopathiae and that appropriate vaccinations subsequently protected the sows from the disease.

Phase-inversion sonography during the liver-specific late phase of contrast enhancement: improved detection of liver metastases.

OBJECTIVE: The purpose of our study was to assess whether phase-inversion sonography during the late, liver-specific phase of contrast enhancement using Levovist improves the detection of hepatic metastases relative to unenhanced conventional B-mode sonography. SUBJECTS AND METHODS: Sixty-two patients were studied with unenhanced B-mode sonography and phase-inversion sonography 2.5 min after the injection of Levovist. All patients underwent one reference examination (CT, MR imaging, or intraoperative sonography). The conspicuity, number, size, and distribution of metastases before and after contrast administration as judged by a sonographer (who was unaware of other imaging findings) were compared with each other and with reference imaging. RESULTS: The conspicuity of metastases was improved by contrast-enhanced phase inversion in 94% of patients. Thirty-nine patients showed metastases on reference imaging; 36 of these were positive on baseline sonography and 38 on phase-inversion sonography. Phase-inversion sonography showed more reference imaging-confirmed metastases than baseline sonography in 28 patients (45%). The average number of confirmed metastases per patient was 3.06 for baseline sonography and 5.42 for contrast-enhanced phase-inversion sonography (p < 0.01). The average sensitivity for detecting individual metastases improved from 63% to 91%. Metastases of less than 1 cm were shown in 14 patients on baseline sonography, in 24 patients on phase-inversion sonography, and in 26 on reference imaging. Both sonographic techniques showed false-positive lesions in six patients. CONCLUSION: Contrast-enhanced phase-inversion sonography in the liver-specific phase of contrast enhancement using Levovist provides a marked improvement in the detection of hepatic metastases relative to unenhanced conventional sonography, without loss of specificity. Phase-inversion sonography was particularly advantageous in detecting small metastases and may be a competitive alternative to CT and MR imaging.

[Ultrasound diagnosis of liver metastases with liver-specific contrast media]. / Sonographie von Lebermetastasen mit leberspezifischem Kontrastmittel.

In recent years sonographic contrast agents which can be used for liver imaging have become available. Some of these agents (e.g. Levovist, Schering AG, Berlin) display a liver-specific late phase. Visualisation of this late phase requires contrast-specific imaging techniques such as phase or pulse inversion. When scanned in phase inversion during the late phase, normal liver parenchyma shows strong enhancement. This enhancement spares metastases which stand out as echo-poor or almost echo-free enhancement defects. This improves the conpicuity of metastases markedly. The technique increases the number of detectable metastases in up 45% of patients in comparison to unenhanced sonography. In a multi-centre study on 128 patients the sensitivity in the detection of individual metastases was increased from 71% to 88% and specificity improved from 59% to 88%. Contrast-enhanced sonography thus represents a promising alternative to other cross-sectional imaging modalities in the diagnosis of hepatic metastases.

B-mode enhancement at phase-inversion US with air-based microbubble contrast agent: initial experience in humans.

Pulse- or phase-inversion ultrasonography (US) sums the signals returned from two 180 degrees ultrasound pulses. Linear scattering from tissue results in a signal void while nonlinear signals from microbubbles stand out. The technique was applied with a US contrast agent in 39 human subjects. B-mode enhancement of vessels and organ parenchyma was seen in all cases. Enhancement occurred from flowing and stationary microbubbles. The flow-independent enhancement of normal and abnormal tissue represents a major advance in contrast material-enhanced US with many potential applications especially in tumor imaging.

[Stimulated acoustic emissions with the ultrasound contrast medium levovist: a clinically useful contrast effect with liver-specific properties]. / Stimulierte akustische Emission mit dem Ultraschall-Kontrastmittel Levovist: Ein klinisch nutzbarer Kontrasteffekt mit leberspezifischen Eigenschaften.

PURPOSE: The purpose of this study was systematically to investigate stimulated acoustic emission (SAE) with the microbubble contrast agent Levovist (Schering AG, Berlin) in vivo with regards to reproducibility, distribution in various organs over time, dependence on technical factors, and influence on the delineation of focal liver lesions. PATIENTS AND METHODS: 2 intravenous injections of 1 g of Levovist were given to 2 dogs and 1-6 injections of 2.5 g Levovist to 5 healthy volunteers and 37 patients. The liver, spleen, large abdominal vessels, and kidney were intermittently scanned for up to 30 min. Studies were evaluated for the presence of SAE signals by 2 observers. In 20 patients with focal liver lesions (15 with metastases, 4 haemangiomata, 1 hepatocellular carcinoma, and 1 cyst) the influence on lesion visualization was also assessed. RESULTS: SAE effects, lasting up to 30 minutes, were seen in all subjects in the liver and spleen. Vascular and renal SAE signals were noted shortly after injection, lasting up to 6 minutes. SAE was absent or markedly reduced in focal liver lesions, which were seen as colour voids. This increased the conspicuity of focal lesions, and in 5 patients additional metastases were detected that could not be delineated on B-mode alone. CONCLUSION: A liver- and spleen-specific late phase of Levovist can be consistently demonstrated using SAE and the effect increases the conspicuity of focal liver lesions.