Addition Of Ultrasound Contrast Agent Research Articles

Correlation of structure and echogenicity of nanoscaled ultrasound contrast agents in vitro

Ultrasound is a common tool for clinical diagnosis due to its safety and economic. Especially the addition of ultrasound contrast agents leads to a high diagnostic reliability. In recent years ultrasound has been used as a trigger for directed drug delivery or to enhance thrombolysis. We developed a nanoscaled ultrasound contrast agent (NUSCA) to improve these applications. In the future drugs can be incorporated into this contrast agent to achieve a combination of ultrasound diagnosis and therapy. The aim of the present study is to elucidate the structure of the nanoscaled lipid formulations and a potential dependence of the ultrasound contrast enhancement on this structure. Our NUSCA is based on the phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and the single-chained polyethylene glycol (40) stearate (PEG40S). In this study the effect of increasing concentrations of the single chained PEG40S on the structure of the lipid formulations was characterised using Dynamic Light Scattering, cryo-Transmission Electron Microscopy, Nuclear Magnetic Resonance spectroscopy, lipid monolayer studies and epifluorescence measurements. In addition, the ultrasound contrast enhancement for the formulations was determined in vitro. Dependence between structure and ultrasound contrast was found. All PEG40S concentrations lead to a mixture of liposomes and discoid micelles. With increasing PEG40S content the amount of micelles increased. Certain PEG40S concentrations lead to an ultrasound contrast superior to the contrast of the commercially available ultrasound contrast agent SonoVue®.

Low-amplitude ultrasound enhances hydrodynamic-based gene delivery to rat kidney

The synergistic combination of hydrodynamic-based gene delivery and ultrasound was investigated to achieve improved gene transfer to the kidney. Plasmids encoding firefly luciferase and Erythropoietin (EPO) gene were delivered into the left kidney of rats by single or combinative application of renal vein hydrodynamic injection and ultrasound treatment with or without the addition of ultrasound contrast agents (UCA). Ultrasound exposure was found to enhance the efficiency of hydrodynamic-based gene delivery for both luciferase and EPO expression. An ultrasound exposure intensity of 2W/cm2 at 10% duty cycle for 15min, produced a maximal gene expression 4.5 times higher than hydrodynamic delivery alone. Duration, location, and tissue-specificity of gene expression were not changed by ultrasound exposure. Application of UCA reduced the intensity and exposure duration of ultrasound treatment needed for optimal expression. Appropriate application of ultrasound and UCA did not alter histological structure or impair physiological function of the treated kidney.

Inertial cavitation dose produced ex vivo in rabbit ear arteries with optison

Ultrasound-induced inertial cavitation (IC) effects were studied ex vivo in rabbit ear arteries with the addition of ultrasound contrast agents (UCAs). Ears were removed from New Zealand white rabbits immediately after being euthanized under a protocol approved by the University of Washington IACUC. The auricular arteries were perfused with varying concentration of UCA (Optison) in saline and exposed to 1.155-MHz pulsed high-intensity focused ultrasound (HIFU) with constant PRF (10 Hz), pulse length (20 cycles), and total treatment time (20 s). Experiments were performed for variable peak negative acoustic pressure (P−) (from 0.19 to 3.31 Mpa) and Optison volume concentration (0% [saline only], 0.1%, 0.2%, 0.5%, and 1%). Cavitation activity was quantified by IC Dose (cumulated root-mean-squared [rms] broadband noise amplitude in a particular band in the frequency domain). The results showed that (1) IC activity was induced much more easily with the addition of Optison, even at low volume concentration, such as 0.1%. (2) IC dose increased significantly with the increasing acoustic pressure and Optison concentration. (3) Higher concentrations of Optison decreased the IC threshold. [Work supported by NIH 8RO1 EB00350-2.]

Focused ultrasound (HIFU) induces localized enhancement of reporter gene expression in rabbit carotid artery.

The development of accurate, safe, and efficient gene delivery remains a major challenge towards the realization of gene therapeutic prevention and treatment of cardiovascular diseases. In this study, we investigated the ability of high-intensity focused ultrasound (HIFU), a form of mechanical wave transmission, to act as a noninvasive tool for the enhancement of in vivo gene transfer into rabbit carotid arteries. Segments of the common carotid arteries of New Zealand white rabbits were isolated and infused with plasmid DNA encoding the reporter beta-galactosidase either with or without the addition of ultrasound contrast agent consisting of small (approximately 2-5 microm) gas-filled human albumin microspheres to augment cavitation. Infused arteries were exposed to pulsed ultrasound for 1 min (frequency 0.85 MHz, burst length 50 ms, repetition frequency 1 Hz, duration 60 s, peak pressure amplitude of 15 MPa). At 6.3 MPa, HIFU enhanced gene expression eight-fold, and 17.5-fold in the presence of contrast. We found increasing amounts of beta-galactosidase expression in the carotid vessel with increasing pressure amplitude. This dose-response relation was present with and without contrast. Without contrast, no vessel damage was detected up to 15 MPa, while the addition of contrast induced side effects above a threshold of 6.3 MPa peak pressure. The entire procedure was feasible and safe for the animals, and the results suggest that HIFU has the potential to assist in the noninvasive spatial regulation of gene transfer into the vascular system.

Effects of lithotripter fields on biological tissues

Biological effects resulting from exposure to lithotripter fields include hemorrhage in soft tissues, such as the kidney, lung, and intestine, the production of premature cardiac contractions, malformations in the chicken embryo, and killing of Drosophila larvae. Pulsed ultrasound can produce similar bioeffects at comparable pressure thresholds. Tissues that contain gas bodies, either naturally or after the addition of ultrasound contrast agents, are particularly susceptible to damage from low-amplitude lithotripter fields. Lung and intestine contain gas naturally and are hemorrhaged by exposure to lithotripter fields on the order of 1 MPa. After the introduction of an ultrasound contrast agent into the vasculature, many organs and tissues, such as the bladder, kidney, fat, muscle, and mesentery, show extensive hemorrhage after exposure to lithotripter pressures less than 2 MPa. Tissues near developing bone are also selectively susceptible to damage from exposure to low-amplitude lithotripter fields. The thresholds for hemorrhage in tissues near developing bone, such as the fetal head, limbs, and ribs, are all less than 1 MPa for exposures with a piezoelectric lithotripter. Cavitation and purely mechanical forces have been investigated as possible mechanisms for these biological effects of lithotripter fields.

Color Doppler ultrasound of the genitourinary tract

This paper discusses the role of color Doppler ultrasonography (CDU) as it applies to the genitourinary tract. CDU is beneficial in evaluating both the native and allograft kidney in the diagnosis of renal arterial and venous stenosis, arteriovenous fistulas, pseudoaneurysms, arterial and venous thrombosis, and in the characterization and staging of renal masses. CDU has redefined the role of ultrasonography in the evaluation of the scrotum as it relates to testicular torsion, inflammatory disorders and varicoceles. Early results of CDU in prostate carcinoma and benign prostate hypertrophy have shown limited success. Identifying and assessing the neurovascular bundle may have an impact on the staging of prostate carcinoma. It is hoped that the future addition of ultrasound contrast agents will further establish the role of color Doppler in the diagnosis of a variety of genitourinary diseases and disorders.