Quantitative Phase Shift Variance Imaging

Molecular ultrasound imaging is based on the detection of contrast agents (microbubbles) targeted to disease specific receptors in the vasculature. By quantifying the amount of the adherent microbubbles a change in the expression of these receptors and thus the disease development can be assessed. Quantification of microbubbles from ultrasound images in vivo was thus far mainly performed by analysis of the image intensity. In this work, the approach of imaging and counting single microbubbles is pursued. Detection of microbubbles is performed with the Phase Shift Variance Imaging technique recently developed in our research group. The detection of single microbubbles is first verified with microbubbles embedded in gelatine phantoms. Subsequently images from microbubbles targeted to VEGFR-2 are acquired from mouse tumor models to validate the method in vivo. The results show that single bubbles can be detected with a contrast-to-background ratio of 50 dB in the phantoms. Concentration estimates show that absolute quantification is possible with the proposed method. Bubble detection could also be verified in vivo; however minor motion and flow artefacts are present in the pre contrast scans.