Transfection effect of microbubbles on cells in superposed ultrasound waves and behavior of cavitation bubble.

The combination of ultrasound and ultrasound contrast agents (UCAs) is able to induce transient membrane permeability leading to direct delivery of exogenous molecules into cells. Cavitation bubbles are believed to be involved in the membrane permeability; however, the detailed mechanism is still unknown. In the present study, the effects of ultrasound and the UCAs, Optison on transfection in vitro for different medium heights and the related dynamic behaviors of cavitation bubbles were investigated.

Hepatic vein transit time of SonoVue: a comparative study with Levovist.

Purpose: To prospectively compare transit times of Levovist and SonoVue in healthy volunteers and patients with biopsy-proved hepatitis C-related liver disease.

Materials And Methods: Institutional review board approval and informed consent were obtained. Forty patients and 25 healthy volunteers were examined.

Pluronic block copolymers: novel functions in ultrasound-mediated gene transfer and against cell damage.

Pluronics have been investigated as vectors for drug and gene delivery in vitro and in vivo and were demonstrated to have high efficiency for gene transfer in vivo. However, they alone do not enhance gene transfer in vitro. We examined three pluronics, F127, L61 and P85, for their effects on ultrasound (US)-mediated gene transfer in three cell lines, 3T3-MDEI, C2C12 and CHO.

Delivery of oligodeoxynucleotides into human saphenous veins and the adjunct effect of ultrasound and microbubbles.

Therapy with naked oligodeoxynucleotides (ODNs, molecular weight: 3000 to 7500) provides an elegant means of modulating gene expression without the problems associated with conventional gene therapy, but the relatively low transfer efficiency on intravascular administration is a limitation to clinical application. Ultrasound, which can be potentiated by microbubbles, shows promise as a method of delivering macromolecules such as plasmid DNA and other transgenes into cells. Since uptake of molecules into cells depends on their molecular weight, it might be expected that the delivery of ODNs, which are relatively small, will be facilitated by ultrasound and microbubbles.

Gene transfer with microbubble ultrasound and plasmid DNA into skeletal muscle of mice: comparison between commercially available microbubble contrast agents.

Purpose: To compare three commercial microbubble contrast agents (Optison, SonoVue, and Levovist) for their effect on gene delivery in skeletal muscle in conjunction with the use of therapeutic ultrasound.

Materials And Methods: The study was approved by the Animal Care and Use Committee. Plasmid DNA (10 microg) encoding green fluorescent protein (GFP) was mixed with microbubbles (or saline control) and injected into the tibialis anterior muscle of mice with and without adjunct ultrasound (1 MHz, 2 W/cm2, 30 seconds, 20% duty cycle).

Can Doppler sonography grade the severity of hepatitis C-related liver disease?

Objective: Many authors have claimed that Doppler sonography indexes are of value in grading and assessing diffuse liver disease. However, there is much controversy regarding the reliability and reproducibility of these techniques. We performed a prospective study to evaluate whether these methods can grade disease in a well-stratified cohort of patients with hepatitis C virus (HCV)-related liver disease.

A novel technique to measure splanchnic transit time using microbubble ultrasound.

Objective: The objective of this study was to measure splanchnic transit time by intravenous injection of a microbubble.

Materials And Methods: Ten volunteers were examined before and after eating. After Doppler indices of splanchnic circulation were obtained, the superior mesenteric artery (SMA) and vein (SMV) were simultaneously interrogated using power Doppler ultrasound after intravenous injection of a microbubble.

Optimisation of ultrasound-mediated gene transfer (sonoporation) in skeletal muscle cells.

Ultrasound (US) is a promising tool for facilitating direct gene transfer to skeletal muscle, but no systematic optimisation study has been performed. We exposed H2K myoblast cells to US with varying intensity of exposure and duration to evaluate its effect on cell viability and transfection efficiency using as endpoints transfection rate, average fluorescence intensity (fluorescence normalised by the number of transfected cells) and overall expression (the product of transfection rate and average fluorescence intensity) as indices. Cell viability decreased with exposure time and intensity, consistent with previous findings.

Evidence for spleen-specific uptake of a microbubble contrast agent: a quantitative study in healthy volunteers.

Purpose: To evaluate the pharmacokinetics of the microbubble contrast agent BR1.

Materials And Methods: Twenty healthy volunteers were injected via arm vein with a 1.2-mL bolus of BR1.

Improved detection of hepatic metastases with pulse-inversion US during the liver-specific phase of SHU 508A: multicenter study.

Purpose: To compare conventional B-mode ultrasonography (US) alone with the combination of conventional B-mode US and contrast material-enhanced (SHU 508A) late-phase pulse-inversion US for the detection of hepatic metastases by using dual-phase spiral computed tomography (CT) as the standard of reference.

Materials And Methods: One hundred twenty-three patients underwent conventional US, US in the liver-specific phase of SHU 508A, and single-section spiral CT. US and CT images were assessed by blinded readers.

Quantitative microbubble enhanced transrectal ultrasound as a tool for monitoring hormonal treatment of prostate carcinoma.

Background: We quantified changes in prostate carcinoma vascularity treated with anti-androgens using color Doppler and power transrectal ultrasound in combination with microbubble contrast agent Levovist.

Methods: Thirty-six men with prostate carcinoma were studied at baseline and at intervals during treatment. At each attendance, Levovist((R)) (10 ml, 300 mg/ml) was given as an iv bolus.

Advances in ultrasound.

Ultrasound (US) has undergone dramatic changes since its inception three decades ago; the original cumbersome B-mode gantry system has evolved into a high resolution real-time imaging system. This review describes both recent advances in ultrasound and contrast media and likely future developments. Technological advances in electronics and computing have revolutionized ultrasound practice with ever expanding applications.

Measuring portal venous perfusion with contrast-enhanced CT: comparison of direct and indirect methods.

Rationale And Objectives: Two algorithms can be used to measure portal venous perfusion (PVP) with contrast material-enhanced single-level liver computed tomography. The "direct" and "indirect" algorithms use data from the portal vein and aorta, respectively. This study compared PVP values obtained with direct and with indirect algorithms in a series of patients.

Initial observations on the effect of irradiation on the liver-specific uptake of Levovist.

The aim of this pilot study was to see if the biodistribution of the microbubble Levovist (SHU 508 A; Schering AG, Berlin) during its liver specific phase is altered by radiotherapy. The mechanism of this liver-specific phase of this agent remains poorly understood. One way of investigating this is to see what effect radiotherapy has on liver uptake, as both Kupffer cell function and vascular endothelial integrity are selectively damaged by irradiation.

Which continuous US scanning mode is optimal for the detection of vascularity in liver lesions when enhanced with a second generation contrast agent?

Objectives: Microbubble echo-enhancers help in the assessment of focal liver masses by enhancing the signal from blood vessels. A variety of linear and nonlinear scanning modes are now available, but it is unclear which is optimal. A controlled comparison was performed during the infusion of such an agent (SonoVue: Bracco, Milan, Italy).

Enhancement characteristics of the microbubble agent Levovist: reproducibility and interaction with aspirin.

We investigated the reproducibility of Doppler enhancement indices following intravenous bolus injections of Levovist (Schering AG, Berlin) microbubbles. We also aimed to determine whether observations from animal studies suggesting that aspirin potentiates microbubble enhancement were reproducible in humans. In five healthy volunteers, time enhancement profiles of Doppler intensity following repeated bolus injections of Levovist were acquired from the common carotid artery, hepatic vein and kidney using spectral and power Doppler before and after oral aspirin (600 mg).