Ultrasound quantification of molecular marker concentration in large blood vessels

Ultrasound-based molecular imaging has been used in pre-clinical studies of cancer and cardiovascular diseases. Current techniques involve the detection of molecularly bound microbubbles through some combination of nonlinear microbubble detection and lengthy waiting periods or low-pass interframe filtering techniques. Non-specific adhesion is typically measured using additional control microbubble injections. In addition to having prolonged protocols, current limitations include the inability to quantify molecular marker concentration in human tissue environments where attenuation and imaging path lengths are highly variable. Consequently, we developed a new modulated Acoustic Radiation Force-based imaging sequence, which can detect targeted adhesion without the requirement of separate control measurements. Results indicate that the metric extracted from the sequence (residual-to-saturation ratio, R_resid) was independent of acoustic pressures and attenuation levels (p > 0.5, n = 10). R_resid exhibited a linear relationship with measured molecular marker concentration (R² > 0.94). Consequently, the feasibility was demonstrated in vitro for quantification of molecular marker concentration in large vessel environments. Additionally, the feasibility of using the modulated ARF-based sequence to separate specific adhesion of adherent microbubbles was also demonstrated in a mouse model of inflammation in vivo.