Microcirculation volumetric flow assessment using high-resolution, contrast-assisted images

To improve the resolution of contrast-assisted imaging systems, we previously developed a 25-MHz microbubbles-destruction/replenishment imaging system with a spatial resolution of 160 X 160 mum. The goal of the present study was to propose a new approach for functionally evaluating the microvascular volumetric blood flow based on this high-frequency, ultrasound imaging system. The approach includes locating the perfusion area and estimating the blood flow velocity therein. Because the correlation changes between before and after microbubble destruction in two adjacent images, a correlated-based approach was introduced to detect the blood perfusion area. We also have derived a new sigmoid-based model for characterizing the microbubbles replenishment process. Two parameters derived from the sigmoid-based model - the rate constant and inflection time - were adopted to evaluate the blood flow velocity. This model was validated using both simulations and in vitro experiments for mean flow velocities ranging from 1 to 10 mm/s, which showed that the model was in good agreement with simulated and measured microbubble-replenishment time-intensity curves. The results indicate that the actual flow velocity is highly correlated with the estimates of the rate constant and the reciprocal of the inflection time. B-mode imaging experiments for mean flow velocities ranging from 0.4 to 2.1 mm/s were used to assess the volumetric flow in the microcirculation. The results indicated the high correlation between the actual volumetric flow rate and the product of the estimated perfusion area and rate constant, and the reciprocal of the inflection time. We also found that the boundary of the microbubble destruction volume significantly affected estimations of the flow velocity. The perfusion area can be located, and the corresponding flow velocity can be estimated simultaneously in a one-stage, microbubble-destruction/replenishment process, which makes the assessment of the volumetric blood flow in the microcirculation feasible using a real-time, high-frequency ultrasound system.