High resolution ultrasound including Elastography and Contrast-Enhanced Ultrasound (CEUS) for early detection and characterization of liver lesions in the humanized tumor mouse model

Abstract

Purpose: In this study we investigated the sensitivity of high resolution ultrasound (HRU) in the detection of small liver tumors and its microcirculation in a humanized tumor mouse model (HTM). These mice develop a complete human immune system and human breast cancer growth in the liver which allows the investigation of antibody based immunotherapies under human like conditions. Method: HTM were generated by the co-transplantation of human breast cancer cells and human hematopoietic stem cells. HRU, Doppler sonography (CCDS), contrast enhanced ultrasound (CEUS) and color-coded elastography were performed on all HTM and confirmed by histopathological assessment. Results: Using HRU and CEUS, noncystic solid liver lesions between 2 and 11 mm (mean 3.5 mm) size were detectable in HTM. Granulomatous areas were identified by B-scan imaging, showing areas of higher stiffness in elastography and areas without contrast media uptake in the late phase (CEUS). In addition, CEUS detected capillary microcirculation of benign and malignant liver lesions smaller than 10 mm. Conclusion: Beyond human breast cancer HTM additionally developed small parenchymal liver lesions, which could be characterized by HRU in combination with CEUS and elastography in-vivo. Nevertheless, the defined diagnoses of solid liver lesions less than 5 mm require confirmation by histopathology.