Current methods for in vivo microvascular imaging (<1 mm) are limited by the tradeoffs between the depth of penetration, resolution, and acquisition time. Ultrasound Doppler approaches combined at elevated frequencies (<7.5 MHz) are able to visualize smaller vasculature and, however, are still limited in the segmentation of lower velocity blood flow from moving tissue. Contrast-enhanced ultrasound (CEUS) has been successful in visualizing changes in microvascular flow at conventional diagnostic ultrasound imaging frequencies (<7.5 MHz). However, conventional CEUS approaches at elevated frequencies have met with limited success, due, in part, to the diminishing microbubble response with frequency. We apply a plane-wave acquisition combined with the non-linear Doppler processing of ultrasound contrast agents at 15 MHz to improve the resolution of microvascular blood flow while compensating for reduced microbubble response. This plane-wave Doppler approach of imaging ultrasound contrast agents also enables simultaneous detection and separation of blood flow in the microcirculation and higher velocity flow in the larger vasculature. We apply singular value decomposition filtering on the nonlinear Doppler signal to orthogonally separate the more stationary lower velocity flow in the microcirculation and higher velocity flow in the larger vasculature. This orthogonal separation was also utilized to improve time-intensity curve analysis of the microcirculation, by removing higher velocity flow corrupting bolus kinetics. We demonstrate the utility of this imaging approach in a rat spinal cord injury model, requiring submillimeter resolution.

中文翻译：

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血流的高频非线性多普勒造影增强超声成像。

目前的方法 体内微血管成像（<1毫米）受限于穿透深度，分辨率和采集时间之间的折衷。在升高的频率（<7.5 MHz）下组合使用的超声多普勒方法能够观察到较小的脉管系统，但是，在运动组织的低速血流分割中仍然受到限制。对比增强超声（CEUS）已成功可视化了常规诊断超声成像频率（<7.5 MHz）下微血管血流的变化。然而，由于频率上微气泡响应的减少，常规的CEUS方法在高频下取得的成功有限。我们将平面波采集与超声造影剂的非线性多普勒处理在15 MHz处结合使用，以提高微血管血流的分辨率，同时补偿减少的微泡反应。这种对超声造影剂进行成像的平面波多普勒方法还可以同时检测和分离微循环中的血流，以及较大脉管系统中的较高速度的血流。我们对非线性多普勒信号应用奇异值分解滤波，以正交分离微循环中更平稳的较低速度流和较大脉管系统中的较高速度流。通过去除较高流速的破坏团注动力学，该正交分离还用于改善微循环的时间强度曲线分析。