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Quantitative contrast-enhanced ultrasound plays an important role in tumor characterization and treatment assessment. Besides established functional ultrasound techniques, ultrasound molecular imaging using microbubbles targeted to disease-associated markers is increasingly being applied in pre-clinical studies. Often, repeated injections of non-targeted or targeted microbubbles during the same imaging session are administered. However, the influence of repeated injections on the accuracy of the quantitative data is unclear. Therefore, in tumor-bearing mice, we investigated the influence of multiple injections of non-targeted microbubbles (SonoVue) on time to peak and peak enhancement in liver and tumor tissue and of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast agents (MicroMarker) on specific tumor accumulation. We found significantly decreasing values for time to peak and a tendency for increased values for peak enhancement after multiple injections. Repeated injections of VEGFR2-targeted microbubbles led to significantly increased tumor accumulation, which may result from the exposure of additional binding sites at endothelial surfaces caused by mechanical forces from destroyed microbubbles., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The present work was originally published in European Radiology and as a PhD thesis at the RWTH Aachen University and was conducted at the Institute for Experimental Molecular Imaging at the RWTH Aachen University., (© Georg Thieme Verlag KG Stuttgart · New York.)

US is a low-cost, real-time imaging modality that is the most used diagnostic tool in paediatric radiology. Reasons include the improved US image quality in children as compared to adults and the demand for avoiding X-rays as much as possible because children are more sensitive to radiation than adults. Stabilized microbubbles have been approved as US contrast agents for adults and show great potential in improving the diagnostic accuracy for many diseases. Initial studies show that in paediatric radiology contrast-enhanced US could also be beneficial for more than just the diagnosis of vesicoureteral reflux, if US contrast agents were approved for children. Molecular US imaging utilizes microbubbles conjugated to biomolecules that target intravascular disease-specific molecules. Many preclinical studies show that molecular US imaging is a highly sensitive tool to detect neovascularisation, inflammation and cardiovascular diseases. Its main advantages are the higher informative value, the longer persistence of the label at the target lesion and the chance to work with lower contrast agent dosages. Now, clinical translation of molecular US appears at the horizon. This review article reports on the current status of molecular US imaging and discusses its potential for paediatric radiology.