In vivo quantification of ultrasound targeted microbubbles to enhance cancer assessment

Contrast-enhanced ultrasound with targeted microbubble contrast agents is an emerging technique for imaging biological processes at the molecular level. The accumulation of targeted microbubbles at tissue sites overexpressing specific molecular markers increases the backscattered signal for noninvasive evaluations of diseases. The aim of this preliminary study was to combine molecular imaging with an in vivo contrast agent quantification to support the early diagnosis of the pathology and to enhance the assessment of neoplastic tissues. Tumor growth was induced by subcutaneous injection of prostate cancer cells in four rats. Microbubbles targeted to tissue factor (TF) were administered. A vascularized region located in proximity to the tumor and centered around the focus depth was analyzed in each animal. The backscattered signals (i.e. the radio-frequency data) were acquired during two different perfusion conditions to evaluate the contribution of attached microbubbles. After image generation by means of a multi-pulse contrast-enhanced technique, a nonlinear regression method based on the support vector machine was employed to estimate the contrast agent concentrations in cubic voxels (1-mm side length). The number of attached microbubbles per mm3 was estimated based on a multi-dimensional vector of features extracted from the processed radio-frequency signals. A significant correlation (p < 0.05) between the size of the tumors and the estimated microbubble concentration was found, thus opening the possibility for combining molecular imaging and contrast agent concentration mapping to refine pathology evaluation