A novel technique for the selective detection of ultrasound contrast agents, called pulse inversion Doppler, has been developed. In this technique, a conventional Doppler or color Doppler pulse sequence is modified by inverting every second transmit pulse. Either conventional or harmonic Doppler processing is then performed on the received echoes. In the resulting Doppler spectra, Doppler shifts from linear and nonlinear scattering are separated into two distinct regions that can be analyzed separately or combined to estimate the ratio of nonlinear to linear scattering from a region of tissue. The maximum Doppler shift that can be detected is 1/2 the normal Nyquist limit. This has the advantage over conventional harmonic Doppler that it can function over the entire bandwidth of the echo signal, thus achieving superior spatial resolution in the Doppler image. In vitro measurements comparing flowing agent and cellulose particles suggest that pulse inversion Doppler can provide 3 to 10 dB more agent to tissue contrast than harmonic imaging with similar pulses. Similar measurements suggest that broadband pulse inversion Doppler can provide up to 16 dB more contrast than broadband conventional Doppler. Nonlinear propagation effects limit the maximum contrast obtainable with both harmonic and pulse inversion Doppler techniques.

We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.bioeffects | contrast agent | vascular disruption | radiosensitization

Contrast agents for ultrasonography (US) comprise microscopic bubbles of gas in an encapsulating shell. They are unique in that they interact with the imaging process, oscillating in response to a low-intensity ultrasound field and disrupting in response to a high-intensity field. New contrast-specific imaging modes allow US to show exquisite vascularity and tissue perfusion in real time and with excellent spatial resolution. In Europe, Asia, and Canada, to name only the most obvious, characterization of focal liver masses is the first and best established use of contrast-enhanced (CE) US, allowing for the noninvasive diagnosis of commonly encountered liver masses with comparable accuracy to that of computed tomography and magnetic resonance studies. CE US is a preferred modality for the difficult task of diagnosis of liver nodules detected on surveillance scans in those at risk for hepatocellular carcinoma. Newer body applications include the guidance of ablative intervention, monitoring activity of bowel inflammation in Crohn disease, characterization of kidney masses, especially cystic renal cell carcinoma, diagnosis of prostate cancer, and monitoring the response of tumors to antivascular drug therapies. Microbubble contrast agents are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. CE US plays a vital and expanding role that improves management and patient care.

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The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.

“How to perform contrast-enhanced ultrasound (CEUS)” provides general advice on the use of ultrasound contrast agents (UCAs) for clinical decision-making and reviews technical parameters for optimal CEUS performance. CEUS techniques vary between centers, therefore, experts from EFSUMB, WFUMB and from the CEUS LI-RADS working group created a discussion forum to standardize the CEUS examination technique according to published evidence and best personal experience. The goal is to standardise the use and administration of UCAs to facilitate correct diagnoses and ultimately to improve the management and outcomes of patients.

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