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Influence of Repetitive Contrast Agent Injections on Functional and Molecular Ultrasound Measurements

Ultrasound in Medicine & Biology
DOI: 10.1016/j.ultrasmedbio.2014.04.010
  • Contrast-Enhanced Ultrasound
  • Molecular Ultrasound
  • Quantitative Imaging
  • Multiple Injections
  • Cancer
  • Sonovue
  • Vascular Endothelial Growth Factor Receptor 2
  • Vegfr2
  • Reproducibility
  • Peak Enhancement
  • Time To Peak
  • Medicine


Abstract 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.

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