The use of super-resolution ultrasound (SR-US) imaging greatly improves visualization of microvascular structures, but clinical adoption is limited by long imaging times. This method depends on detecting and localizing isolated microbubbles (MBs), forcing the use of a dilute contrast agent concentration. Contrast-enhanced ultrasound (CEUS) image acquisition times as long as minutes arise as the localization of thousands of MBs are acquired to form a complete SR-US image. In this article, we explore the use of nonlinear CEUS strategies using nonlinear fundamental contrast pulse sequencing (CPS) to increase the contrast-to-tissue ratio (CTR) and compare MB detection effectiveness to linear B-mode CEUS imaging. The CPS compositions of amplitude modulation (AM), pulse inversion (PI), and a combination of the two (AMPI) were studied. A simulation study combined the Rayleigh-Plesset-Marmottant (RPM) model of MB characteristics and a nonlinear tissue model using the k-Wave toolbox for MATLAB (MathWorks Inc., Natick, MA, USA). Validation was conducted using an in vitro flow phantom and in vivo in the rat hind-limb. Imaging was performed with a programmable US scanner (Vantage 256, Verasonics Inc., Kirkland, WA, USA) and customized to transmit a set of basis US pulses from which both B-mode US (frame rate (FR) of 800 Hz) and multiple nonlinear CPS compositions (FR of 200 Hz) could be assessed from identical in vitro and in vivo datasets using a near simultaneous method. The simulations suggest that MB characteristics, such as diameter and motion, help to predict which US imaging strategy will enhance MB detection. The in vitro and in vivo US imaging studies revealed that different subpopulations of polydisperse MB contrast agents were detected by linear imaging and by each different nonlinear CPS composition. The most effective single imaging strategy at a 200-Hz FR was found to be B-mode US imaging. However, a combination of B-mode US imaging with a nonlinear CPS imaging strategy was more effective in detecting MBs in vivo at all depths and was shown to shorten image acquisition time by an average of 33.3%-76.7% when combining one or more CPS sequences.

中文翻译：

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用于超分辨率超声成像的非线性对比脉冲测序的评估。


超分辨率超声（SR-US）成像的使用极大地改善了微血管结构的可视化，但临床应用因成像时间长而受到限制。该方法依赖于检测和定位孤立的微泡 (MB)，从而强制使用稀释的造影剂浓度。由于要采集数千个 MB 的定位以形成完整的 SR-US 图像，因此对比增强超声 (CEUS) 图像采集时间长达几分钟。在本文中，我们探讨了非线性 CEUS 策略的使用，该策略使用非线性基本对比脉冲测序 (CPS) 来提高对比组织比 (CTR)，并将 MB 检测效果与线性 B 模式 CEUS 成像进行比较。研究了调幅 (AM)、脉冲反转 (PI) 和两者组合 (AMPI) 的 CPS 组成。一项模拟研究使用 MATLAB 的 k-Wave 工具箱（MathWorks Inc.，Natick，MA，USA）将 MB 特性的 Rayleigh-Plesset-Marmottant (RPM) 模型与非线性组织模型结合起来。使用体外流动模型和大鼠后肢体内进行验证。使用可编程 US 扫描仪（Vantage 256，Verasonics Inc.，柯克兰，华盛顿州，美国）进行成像，并定制传输一组基础 US 脉冲，其中 B 模式 US（帧速率 (FR) 为 800 Hz）和可以使用近乎同步的方法从相同的体外和体内数据集中评估多种非线性 CPS 成分（200 Hz 的 FR）。模拟表明，MB 特征（例如直径和运动）有助于预测哪种 US 成像策略将增强 MB 检测。 体外和体内 US 成像研究表明，通过线性成像和每种不同的非线性 CPS 组合物可以检测到多分散 MB 造影剂的不同亚群。研究发现，200 Hz FR 下最有效的单一成像策略是 B 模式 US 成像。然而，B 模式 US 成像与非线性 CPS 成像策略的组合在检测体内所有深度的 MB 时更有效，并且当组合一种或多种 CPS 时，图像采集时间平均缩短 33.3%-76.7%序列。