Nonlinear ultrasound imaging of the microcirculation

Blood flow at and near the tissue level is a physiological parameter of significant experimental and clinical importance, as it reflects the adaptive response of organs to their normal biological environment, to disease, trauma, and the malignant progression of cancer. The use of microbubbles gives ultrasound imaging access to microvascular hemodynamics, which are beyond the ability of Doppler ultrasound methods. However, expanded clinical use of microbubbles has been limited due in part to a lack of quantification and providing only relative differences in microvascular flow. Past and more recent approaches to the quantification of microvascular blood flow will be presented. Past approaches included the use of focused nonlinear pulsing sequences to isolate microbubble from tissue signals followed by analysis of bolus kinetics or flash replenishment dynamics. Although successfull to some extent, their clinical limitations prohibited extended use and the overall application of contrast enhanced ultrasound (CEUS). Newer approaches include higher frame-rate plane wave acquisitions combined with nonlinear pulsing schemes, which enable the tracking of microbubble flow through microvascular networks. Different approaches of these elevated frame-rate acquisitions will be presented, including use of ultrasound localized microscopy.