Low-frequency ultrasound increases non-viral gene transfer to the mouse lung.

The aim of the study was to assess if low-frequency ultrasound (US), in the range of 30-35 kHz, increases non-viral gene transfer to the mouse lung. US is greatly attenuated in the lung due to large energy losses at the air/tissue interfaces. The advantages of low-frequency US, compared with high-frequency US are: (i) increased cavitation (responsible for the formation of transient pores in the cell membrane) and (ii) reduced energy losses during lung penetration.

Comparative study of experienced vs non-experienced radiologists in assessing parametric CT images of the response of the prostate gland to radiotherapy.

Functional CT can demonstrate acute quantitative increases in perfusion, permeability and fractional vascular volume in the prostate gland of patients with prostate cancer following radiotherapy (RT). We hypothesize that these quantitative changes can also be demonstrated visually by presenting them as colour parametric maps using custom software. 21 patients with prostate cancer were studied before, and 1-2 weeks after, RT.

Can contrast-enhanced ultrasonography characterize focal liver lesions and differentiate between benign and malignant, thus providing a one-stop imaging service for patients?().

Purpose: Contrast-enhanced ultrasonography (CEUS) displays high sensitivity and specificity in characterizing focal liver lesions (FLLs). We attempted to determine how often CEUS provides an unequivocal diagnosis of FLLs that does not require additional imaging studies.

Materials And Methods: Seventy-three patients with 146 FLLs were scanned with B-mode, Doppler, and contrast-enhanced US (2 × 2.

Use of ultrasound to enhance nonviral lung gene transfer in vivo.

We have assessed if high-frequency ultrasound (US) can enhance nonviral gene transfer to the mouse lung. Cationic lipid GL67/pDNA, polyethylenimine (PEI)/pDNA and naked plasmid DNA (pDNA) were delivered via intranasal instillation, mixed with Optison microbubbles, and the animals were then exposed to 1 MHz US. Addition of Optison alone significantly reduced the transfection efficiency of all three gene transfer agents.

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.

Ultrasonographic and radiographic results from a two-year controlled trial of immediate or one-year-delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis.

Objective: To compare the impact of immediate and delayed introduction of anti-tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA).

Methods: Twenty-four patients with erosive early RA (duration < 3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg.

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.

Cyclosporine A does not alter ultrasonic indices of renal blood flow: a potential tool for differentiating toxicity from acute rejection?

The narrow therapeutic window of cyclosporine A (CsA) means its use is controlled by pharmacokinetic monitoring. However, pharmacokinetics do not always reflect the functional effects of a drug--its pharmacodynamics, such as vasoconstriction. We developed a technique for measuring renal blood flow and used a pig model to determine whether CsA-induced renal vasoconstriction could be detected, thus offering a tool for pharmacodynamic therapeutic drug monitoring.

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.

Hepatic vein transit times using a microbubble agent can predict disease severity non-invasively in patients with hepatitis C.

Background And Aims: A reliable non-invasive assessment of the severity of diffuse liver disease is much needed. We investigated the utility of hepatic vein transit times (HVTT) for grading and staging diffuse liver disease in a cohort of patients with hepatitis C virus (HCV) infection using an ultrasound microbubble contrast agent as a tracer.

Materials And Methods: Eighty five untreated patients with biopsy proven HCV induced liver disease were studied prospectively.

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.

The role of ultrasound in molecular imaging.

Ultrasound has received less attention than other imaging modalities for molecular imaging, but has a number of potential advantages. It is cheap, widely available and portable. Using Doppler methods, flow information can be obtained easily and non-invasively.

Transdermal estradiol improves bone density when used as single agent therapy for prostate cancer.

Purpose: Current androgen deprivation therapies for men with prostate cancer cause accelerated osteoporosis and a significant risk of osteoporotic fracture. We have recently shown that transdermal estradiol is an effective alternative for such patients. Here we report the impact of transdermal estradiol therapy on the bone mineral density of men with prostate cancer.

Improved characterization of liver lesions with liver-phase uptake of liver-specific microbubbles: prospective multicenter study.

Purpose: To evaluate in a prospective multicenter study whether conventional ultrasonographic (US) characterization of liver lesions can be improved by imaging during the liver-specific phase of SH U 508A uptake in the microbubble-specific agent detection imaging mode.

Materials And Methods: One hundred forty-two patients with liver lesions underwent conventional gray-scale and color Doppler US and SH U 508A-enhanced US. Two radiologists blindly read digital cine clips and assigned scores for confidence in diagnosis of benignancy or malignancy, diagnosis of specific lesion types, and relative difference in SH U 508A uptake between the lesion and the liver parenchyma (ie, subjective conspicuity score [SCS]).