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A Special Collection of Papers from the 25th European Symposium on Ultrasound Contrast Imaging
Contrast-Enhanced High-Frame-Rate Ultrasound Imaging of Flow Patterns in Cardiac Chambers and Deep Vessels
Cardiac function and vascular function are closely related to the flow of blood within. The flow velocities in these larger cavities easily reach 1 m/s, and generally complex spatiotemporal flow patterns are involved, especially in a non-physiologic state. Visualization of such flow patterns using ultrasound can be greatly enhanced by administration of contrast agents. Tracking the high-velocity complex flows is challenging with current clinical echographic tools, mostly because of limitations in signal-to-noise ratio; estimation of lateral velocities; and/or frame rate of the contrast-enhanced imaging mode.Ultrasound Contrast Agent Modeling: A Review
Ultrasound is extensively used in medical imaging, being safe and inexpensive and operating in real time. Its scope of applications has been widely broadened by the use of ultrasound contrast agents (UCAs) in the form of microscopic bubbles coated by a biocompatible shell. Their increased use has motivated a large amount of research to understand and characterize their physical properties as well as their interaction with the ultrasound field and their surrounding environment. Here we review the theoretical models that have been proposed to study and predict the behavior of UCAs.Microbubble Agents: New Directions
Microbubble ultrasound contrast agents have now been in use for several decades and their safety and efficacy in a wide range of diagnostic applications have been well established. Recent progress in imaging technology is facilitating exciting developments in techniques such as molecular, 3-D and super resolution imaging and new agents are now being developed to meet their specific requirements. In parallel, there have been significant advances in the therapeutic applications of microbubbles, with recent clinical trials demonstrating drug delivery across the blood–brain barrier and into solid tumours.Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery
Therapeutic ultrasound strategies that harness the mechanical activity of cavitation nuclei for beneficial tissue bio-effects are actively under development. The mechanical oscillations of circulating microbubbles, the most widely investigated cavitation nuclei, which may also encapsulate or shield a therapeutic agent in the bloodstream, trigger and promote localized uptake. Oscillating microbubbles can create stresses either on nearby tissue or in surrounding fluid to enhance drug penetration and efficacy in the brain, spinal cord, vasculature, immune system, biofilm or tumors.Vibrating Bubbles, Brilliant Images and Palpable Therapeutics
It all started in the late eighties of the last century. Real time 2D medical ultrasound imaging was established and color Doppler turned out to have excellent diagnostic utility in the larger vessels and cavities like the atria and ventricles of the heart. For visualising smaller vessels, however, there was a clear need for a contrast agent to rescue the Doppler signal. Microbubbles were the obvious candidates, since it was known that small bubbles reflect ultrasound strongly. Very quickly, several pharmaceutical and start-up companies introduced gas filled microbubbles for intravenous administration.New Applications in Echocardiography for Ultrasound Contrast Agents in the 21st Century
Contrast echocardiography microbubbles are ultrasound-enhancing agents that were originally designed to help improve endocardial border definition, known as left ventricle opacification, and to enhance Doppler signals. Over time, contrast microbubbles are used to assess myocardial perfusion because they travel through the capillaries of the cardiac circulation. Current research provides good evidence that myocardial perfusion echocardiography improves comprehensive echocardiographic evaluations of ischemic heart disease.Contrast-Enhanced Ultrasound of Focal Liver Masses: A Success Story
The epidemic of increasing fatty liver disease and liver cancer worldwide, and especially in Western society, has given new importance to non-invasive liver imaging. Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents provides unique advantages over computed tomography (CT) and magnetic resonance imaging (MRI), the currently established methods. CEUS provides determination of malignancy and allows excellent differential diagnosis of a focal liver mass, based on arterial phase enhancement patterns and assessment of the timing and intensity of washout.Super-resolution Ultrasound Imaging
The majority of exchanges of oxygen and nutrients are performed around vessels smaller than 100 μm, allowing cells to thrive everywhere in the body. Pathologies such as cancer, diabetes and arteriosclerosis can profoundly alter the microvasculature. Unfortunately, medical imaging modalities only provide indirect observation at this scale. Inspired by optical microscopy, ultrasound localization microscopy has bypassed the classic compromise between penetration and resolution in ultrasonic imaging.Contrast-Enhanced Ultrasound Quantification: From Kinetic Modeling to Machine Learning
Ultrasound contrast agents (UCAs) have opened up immense diagnostic possibilities by combined use of indicator dilution principles and dynamic contrast-enhanced ultrasound (DCE-US) imaging. UCAs are microbubbles encapsulated in a biocompatible shell. With a rheology comparable to that of red blood cells, UCAs provide an intravascular indicator for functional imaging of the (micro)vasculature by quantitative DCE-US. Several models of the UCA intravascular kinetics have been proposed to provide functional quantitative maps, aiding diagnosis of different pathological conditions.Three Decades of Ultrasound Contrast Agents: A Review of the Past, Present and Future Improvements
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.Seeing the Invisible—Ultrasound Molecular Imaging
Ultrasound molecular imaging has been developed in the past two decades with the goal of non-invasively imaging disease phenotypes on a cellular level not depicted on anatomic imaging. Such techniques already play a role in pre-clinical research for the assessment of disease mechanisms and drug effects, and are thought to in the future contribute to earlier diagnosis of disease, assessment of therapeutic effects and patient-tailored therapy in the clinical field. In this review, we first describe the chemical composition and structure as well as the in vivo behavior of the ultrasound contrast agents that have been developed for molecular imaging.Imaging Methods for Ultrasound Contrast Agents
Microbubble contrast agents were introduced more than 25 years ago with the objective of enhancing blood echoes and enabling diagnostic ultrasound to image the microcirculation. Cardiology and oncology waited anxiously for the fulfillment of that objective with one clinical application each: myocardial perfusion, tumor perfusion and angiogenesis imaging. What was necessary though at first was the scientific understanding of microbubble behavior in vivo and the development of imaging technology to deliver the original objective.Contrast-Enhanced Ultrasound to Assess Carotid Intraplaque Neovascularization
Contrast-enhanced ultrasound (CEUS) is increasingly being used to identify patients with carotid plaques that are vulnerable to rupture, so-called vulnerable atherosclerotic plaques, by assessment of intraplaque neovascularization. A complete overview of the strengths and limitations of carotid CEUS is currently not available. The aim of this systematic review was to provide a complete overview of existing publications on the role of CEUS in assessment of carotid intraplaque neovascularization. The systematic review of the literature yielded 52 studies including a total of 4660 patients (mean age: 66 y, 71% male) who underwent CEUS for the assessment of intraplaque neovascularization.
