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Ultrasound contrast agents (UCA), in conjunction with contrast specific imaging techniques, are increasingly accepted in clinical use for diagnostic imaging and post-interventional workup in several organs. Presently, there is no guidance document providing a description of essential technical requirements, proposed investigator qualifications, suggested investigational procedures and steps, guidance on image interpretation, recommended and established clinical indications and safety considerations.The need for these guidelines was highlighted following the EFSUMB Board of Directors (Delegates) meeting at the EUROSON Congress at Copenhagen in March, 2003. During their development these guidelines were presented at the EFSUMB special consensus meeting for the use of contrast agents in ultrasound

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Many Doppler imaging studies have been performed in recent years in a large number of ocular disorders because of improvements in the Doppler equipment used for detecting and measuring the low blood-flow velocities that are a requisite for the quantitative evaluation of blood flow in the orbital vessels. The ophthalmic artery, central retinal artery and vein, posterior ciliary arteries, and the superior ophthalmic vein can be easily identified using color Doppler sonography. The changes in local blood flow in these vessels assessed by spectral analysis pulsed Doppler sonography have been used to characterize and to obtain new insights into different nontumoral vascular disorders including carotid artery stenosis, central retinal vein occlusion, giant cell arteritis, glaucoma, diabetes, fistulas, and tumoral processes of the eye and orbit. Our experience has confirmed the important role of Doppler sonography in the assessment of subclinical changes in the vascular bed, in the understanding of different processes, for following up after specific treatments, and for determining the long-term prognosis of these various conditions.

Initial reports from the 1960s describing the observations of ultrasound contrast enhancement by tiny gaseous bubbles during echocardiographic examinations prompted the development of the first ultrasound contrast agent in the 1980s. Current commercial contrast agents for echography, such as Definity, Optison, Sonazoid and SonoVue, have proven to be successful in a variety of on-and off-label clinical indications. Whereas contrast-specific technology has seen dramatic progress after the introduction of the first approved agents in the 1990s, successful clinical translation of new developments has been limited during the same period, while understanding of microbubble physical, chemical and biologic behavior has improved substantially. It is expected that for a successful development of future opportunities, such as ultrasound molecular imaging and therapeutic applications using microbubbles, new creative developments in microbubble engineering and production dedicated to further optimizing microbubble performance are required, and that they cannot rely on bubble technology developed more than 3 decades ago.

In young healthy adults, ultrasonography appeared to be a reliable tool to assess the diameter of the subglottic upper airway.

While there is an increasing role of ultrasound for breast cancer screening in patients with dense breast, conventional anatomical-ultrasound lacks sensitivity and specificity for early breast cancer detection. In this study we assessed the potential of molecular-ultrasound imaging, using clinically-translatable vascular endothelial growth factor receptor (VEGFR2)-targeted microbubbles (MBVEGFR2), to improve the diagnostic accuracy of ultrasound in earlier detection of breast cancer and ductal carcinoma in situ (DCIS) in a transgenic mouse model (FVB/N-Tg(MMTV-PyMT)634Mul). In vivo binding specificity studies (n=26 tumors) showed that ultrasound imaging signal was significantly higher (P<0.001) using MBVEGFR2 compared to non-targeted microbubbles and imaging signal significantly decreased (P<0.001) by blocking antibodies. Ultrasound molecular imaging signal significantly increased (P<0.001), when breast tissue (n=315 glands) progressed from normal (1.65±0.17 a.u.) to hyperplasia (4.21±1.16), DCIS (15.95±1.31) and invasive cancer (78.1±6.31) and highly correlated with ex vivo VEGFR2 expression (R2=0.84; 95% CI, 0.72, 0.91; P<0.001). At an imaging signal threshold of 4.6 a.u., ultrasound molecular imaging differentiated benign from malignant entities with a sensitivity of 84% (95% CI, 78, 88) and specificity of 89% (95% CI, 81, 94). In a prospective screening trail (n=63 glands) diagnostic performance of detecting DCIS and breast cancer was assessed and two independent readers correctly diagnosed malignant disease in >95% of cases and highly agreed between each other (ICC=0.98; 95% CI, 97, 99). These results suggest that VEGFR2-targeted ultrasound molecular imaging allows highly accurate detection of DCIS and breast cancer in transgenic mice and may be a promising approach for early breast cancer detection in women.

With contrast-enhanced ultrasound (CEUS) now established as a valuable imaging modality for many applications, a more specific demand has recently emerged for quantifying perfusion and using measured parameters as objective indicators for various disease states. However, CEUS perfusion quantification remains challenging and is not well integrated in daily clinical practice. The development of VueBox™ alleviates existing limitations and enables quantification in a standardized way. VueBox™ operates as an off-line software application, after dynamic contrast-enhanced ultrasound (DCE-US) is performed. It enables linearization of DICOM clips, assessment of perfusion using patented curve-fitting models, and generation of parametric images by synthesizing perfusion information at the pixel level using color coding. VueBox™ is compatible with most of the available ultrasound platforms (nonlinear contrast-enabled), has the ability to process both bolus and disruption-replenishment kinetics loops, allows analysis results and their context to be saved, and generates analysis reports automatically. Specific features have been added to VueBox™, such as fully automatic in-plane motion compensation and an easy-to-use clip editor. Processing time has been reduced as a result of parallel programming optimized for multi-core processors. A long list of perfusion parameters is available for each of the two administration modes to address all possible demands currently reported in the literature for diagnosis or treatment monitoring. In conclusion, VueBox™ is a valid and robust quantification tool to be used for standardizing perfusion quantification and to improve the reproducibility of results across centers.