High frequency ultrasound speckle flow imaging - comparison with Doppler optical coherence tomography (DOCT)

Visualization of the microcirculation can provide important diagnostic and therapeutic monitoring information in vascular and neoplastic diseases. Previously, we described a Doppler optical coherence tomography (DOCT) system with a minimum detectable velocity of ∼0.5 mm/s at 32 fps with limited imaging depth (∼2 mm). High frequency ultrasound (>40 MHz) has deeper penetration; however, real-time visualization of slow blood flow is difficult to achieve. We aim to develop a noninvasive ultrasound technique for microvascular imaging of slow flowing blood. We describe a speckle-variance flow processing (SFP) algorithm based on detecting the changes in B-mode pixel intensity on a high frequency ultrasound (HFUS) system operating at 40-60 MHz. The velocity sensitivity of the algorithm was determined by a flow phantom using blood-mimicking fluid. In in vivo experiments, microcirculation in the tadpole cardiovascular system and superficial tumor blood flow in mouse were observed using HFUS SFP to compare its performance to DOCT. The velocity sensitivity was 0.2 mm/s at 30 fps, and the SFP index shows a nonlinear relationship with flow velocity. Microcirculation in deeper structures, such as mouse kidney, was demonstrated. To our knowledge, this is the first demonstration of real-time microcirculation imaging using a non-Doppler HFUS. The velocity sensitivity and spatial resolution of such a system approaches that of DOCT with improved depth penetration, and can he utilized to visualize slow blood flow in the microcirculation of small animals and humans.