Characterization of spatially mapped volumetric molecular ultrasound signals for predicting response to anti-vascular therapy

Quantitative three-dimensional molecular ultrasound is a promising technology for longitudinal imaging applications such as therapy monitoring; the risk profile is favorable compared to positron emission tomography and computed tomography. However, clinical translation of quantitative methods for this technology are limited in that they assume that tumor tissues are homogeneous, and often depend on contrast-destruction events that can produce unintended bioeffects. Here, we develop quantitative features (henceforth image features) that capture tumor spatial information, and that are extracted without contrast destruction. We compare these techniques with the contrast-destruction derived differential targeted enhancement parameter (dTE) in predicting response to therapy. We found thirty-three reproducible image features that predict response to antiangiogenic therapy, without the need for a contrast agent disruption pulse. Multiparametric analysis shows that several of these image features can differentiate treated versus control animals with comparable performance to post-destruction measurements, suggesting that these can potentially replace parameters such as the dTE. The highest performing pre-destruction image features showed strong linear correlations with conventional dTE parameters with less overall variance. Thus, our study suggests that image features obtained during the wash in of the molecular agent, pre-destruction, may replace conventional post-destruction image features or the dTE parameter.