Department of Biomedical Engineering, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands.
IEEE Trans Ultrason Ferroelectr Freq Control. 2013 Jan;60(1):7-20. doi: 10.1109/TUFFC.2013.2533.
The merits of ultrasound contrast agents (UCAs) were already known in the 1960s. It was, however, not until the 1990s that UCAs were clinically approved and marketed. In these years, it was realized that the UCAs are not just efficient ultrasound scatterers, but that their main constituent, the coated gas microbubble, acts as a nonlinear resonator and, as such, is capable of generating harmonic energy. Subharmonic, ultraharmonic, and higher harmonic frequencies of the transmitted ultrasound frequency have been reported. This opened up new prospects for their use and several detection strategies have been developed to exploit this harmonic energy to discriminate the contrast bubbles from surrounding tissue. This insight created a need for tools to study coated bubble behavior in an ultrasound field and the first models were developed. Since then, 20 years have elapsed, in which a broad range of UCAs and UCA models have been developed. Although the models have helped in understanding the responses of coated bubbles, the influence of the coating has not been fully elucidated to date and UCA models are still being improved. The aim of this review paper is to offer an overview in these developments and indicate future directions for research.
超声造影剂（UCAs）的优点早在 20 世纪 60 年代就已为人所知。然而，直到 20 世纪 90 年代，UCAs 才获得临床批准并上市。在这些年中，人们意识到 UCAs 不仅是有效的超声散射体，而且它们的主要成分——包裹气体微泡，还充当非线性谐振器，因此能够产生谐波能量。已报道了发射超声频率的次谐波、超谐波和更高谐波频率。这为它们的使用开辟了新的前景，并开发了几种检测策略来利用这种谐波能量来区分造影气泡与周围组织。这一见解促使人们需要研究工具来研究超声场中的包裹气泡行为，于是第一批模型应运而生。自那时以来，已经过去了 20 年，在此期间，已经开发出了广泛的 UCAs 和 UCA 模型。尽管这些模型有助于了解包裹气泡的响应，但迄今为止，涂层的影响尚未完全阐明，UCA 模型仍在不断改进。本文的目的是概述这些发展，并指出未来的研究方向。
