Abstract
Three-dimensional high-frequency ultrasound (HF-US) combined with nanobubbles (NBs) permit detection of vessels in tumor. Description of the vessel density in tumors has recently been used for differentiating benign from malignant disease, but it was rarely reported in detection of liver metastases. In this study, we aimed to evaluate the possibility of detecting liver metastases at a minimum size, by evaluation the vessel density in the preclinical liver metastatic models with three-dimensional HF-US and NBs longitudinally. Tumor cells with luciferase-expressing were injected into the spleen slowly to establish the liver metastases models. Liver metastases were confirmed by luciferase activity located in the mouse liver area which was measured by in vivo bioluminescence system (IVIS). Ultrasound imaging on mice livers was performed by a high-frequency ultrasound system after NBs were administered from the tail vein. Vessels in the liver were constructed and the vessel density in the whole liver was calculated by the contrast mode soft. Contrast ultrasound images showed the change of vessels in normal and metastatic parts of liver with time. Vessel density could used to compare the angiogenesis in the metastatic mouse liver with the normal livers. These results demonstrated a system of HF-US combined with NBs could be useful for detection of liver metastases at a minimum size by evaluation the vessel density.
