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. And indeed, for more than 25 years bubble science and imaging technology have evolved methodically to deliver contrast-enhanced ultrasound. Realization of the basic bubbles properties, non-linear response and ultrasound-induced destruction, has led to a plethora of methods; algorithms and techniques for contrast-enhanced ultrasound (CEUS) and imaging modes such as harmonic imaging, harmonic power Doppler, pulse inversion, amplitude modulation, maximum intensity projection and many others were invented, developed and validated. Today, CEUS is used everywhere in the world with clinical indications both in cardiology and in radiology, and it continues to mature and evolve and has become a basic clinical tool that transforms diagnostic ultrasound into a functional imaging modality. In this review article, we present and explain in detail bubble imaging methods and associated artifacts, perfusion quantification approaches, and implementation considerations and regulatory aspects.