Abstract
The development of microbubble contrast agents has broadened the scope of medical ultrasound imaging. Along with dedicated imaging techniques, these agents provide enhanced echoes from the blood pool and have enabled diagnostic ultrasound to assess and quantify microvascular blood flow. Contrast-enhanced ultrasound is currently used worldwide with clinical indications in cardiology and radiology, and it continues to evolve and develop through innovative technological advancements. In this review article, we present an overview of the basic microbubble physics and bubble-specific imaging techniques that enable this modality, and follow this with a discussion on new and emerging applications.
Highlights
Ultrasound imaging is a well-established clinical tool for the morphological assessment of soft tissues, employed frequently in obstetrics, cardiology, and radiology [1]
While the rheological characteristics of phospholipid encapsulated microbubbles results in much larger resonant shifts (~0.07–0.24 MHz per 10 mmHg [123]) that may be sufficiently detectable for clinical utility, major advances in this application of remote blood pressure estimation are derived from investigations into the modulation of subharmonic scattering
These programmable systems give access to the prebeamformed time-domain data (RF data), whereby assuming a single source, the signal time delay τ as a function of array position x produced by a single microbubble echo propagating at a constant speed c is given by: FIGURE 4 | (A) An example of ULM applied in a rat brain through a thinned, intact skull providing a resolution of 10 μm × 8 μm in depth and lateral direction, respectively. (B) In-plane velocity map from parts of the vessel from panel A
Summary
Ultrasound imaging is a well-established clinical tool for the morphological assessment of soft tissues, employed frequently in obstetrics, cardiology, and radiology [1]. The relative motion of red blood cells compared to the surrounding tissue can be exploited to assess blood velocity using Doppler techniques [3], a strategy employed in many clinical applications (e.g., obstetrics [4], assessment of peripheral artery disease [5], cardiology [6]). Recent metaanalysis surveying microbubble tolerance indicates that the dominant cause of severe adverse effects is pseudoanaphylaxis (CARPA), with an estimated rate on the order of 0.004%–0.009% [13] This rate is comparable to most analgesics and antibodies (0.005%–0.015% [14]), and similar if not lower than for other contrast imaging agents, e.g., CT with a rate of 0.04% [15], MR with a rate of 0.002%–0.005% [16, 17]. Note that this is not a comprehensive review, rather an overview of the critical work that has defined this modality and salient investigations into new and ground-breaking applications
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