Dynamic Contrast Enhanced Ultrasound (DCE-US) is an imaging technique that utilizes microbubble contrast agents in diagnostic ultrasound. The EFSUMB guidelines published in 2004, updated in 2008 and 2011 focused on the use of DCE-US, including essential technical requirements, training, investigational procedures and steps, guidance on image interpretation, established and recommended clinical indications and safety considerations. However the quantification of images acquired with ultrasound contrast agents (UCAs) is not discussed in the guidelines. The purpose of this EFSUMB document is to provide some recommendations and descriptions of the quantification of ultrasound images, technical requirements for analysis of time-intensity curves (TICs), methodology for data analysis, and interpretation of the results.

“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.

Diagnostic ultrasound contrast agents have been developed for enhancing the echogenicity of blood and for delineating other structures of the body. Approved agents are suspensions of gas bodies (stabilized microbubbles), which have been designed for persistence in the circulation and strong echo return for imaging. The interaction of ultrasound pulses with these gas bodies is a form of acoustic cavitation, and they also may act as inertial cavitation nuclei. This interaction produces mechanical perturbation and a potential for bioeffects on nearby cells or tissues. In vitro, sonoporation and cell death occur at mechanical index (MI) values less than the inertial cavitation threshold. In vivo, bioeffects reported for MI values greater than 0.4 include microvascular leakage, petechiae, cardiomyocyte death, inflammatory cell infiltration, and premature ventricular contractions and are accompanied by gas body destruction within the capillary bed. Bioeffects for MIs of 1.9 or less have been reported in skeletal muscle, fat, myocardium, kidney, liver, and intestine. Therapeutic applications that rely on these bioeffects include targeted drug delivery to the interstitium and DNA transfer into cells for gene therapy. Bioeffects of contrast-aided diagnostic ultrasound happen on a microscopic scale, and their importance in the clinical setting remains uncertain.

Indicator dilution methods have a long history in the quantification of both macro- and microvascular blood flow in many clinical applications. Various models have been employed in the past to isolate the primary pass of an indicator after an intravenous bolus injection. The use of indicator dilution techniques allows for the estimation of hemodynamic parameters of a tumor or organ and thus may lead to useful diagnostic and therapy monitoring information. In this paper, we review and discuss the properties of the lognormal function, the gamma variate function, the diffusion with drift models, and the lagged normal function, which have been used to model indicator dilution curves in different fields of medicine. We fit these models to contrast-enhanced ultrasound time-intensity curves from liver metastases and the ovine corpora lutea. We evaluate the models' performance on the image data and compare their predictions for hemodynamic-related parameters such as the area under the curve, the mean transit time, the full-width at half-maximum, the time to the peak intensity, and wash-in time. The models that best fit the experimental data are the lognormal function and the diffusion with drift.