Use of 3-D Contrast-Enhanced Ultrasound to Evaluate Tumor Microvasculature After Nanoparticle-Mediated Modulation

Ultrasound Med Biol. 2020 Feb;46(2):369-376. doi: 10.1016/j.ultrasmedbio.2019.09.019. Epub 2019 Nov 4.


A cost-effective method for serial in vivo imaging of tumor microvasculature has been developed. We evaluated acoustic angiography (AA) for visualizing and assessing non-small cell lung tumor (A549) microvasculature in mice before and after tumor vascular disruption by vascular-targeted gold nanoparticles and radiotherapy. Standard B-mode and microbubble-enhanced AA images were acquired at pre- and post-treatment time points. Using these modes, a new metric, 50% vessel penetration depth, was developed to characterize the 3-D spatial heterogeneity of microvascular networks. We observed an increase in tumor perfusion after radiation-induced vascular disruption, relative to control animals. This was also visualized in vessel morphology mode, which revealed a loss in vessel integrity. We found that tumors with poorly perfused vasculature at day 0 exhibited a reduced growth rate over time. This suggested a new method to reduce in-group treatment response variability using pre-treatment microvessel maps to objectively identify animals for study removal.

Keywords: Acoustic angiography; Gold nanoparticles; Microvasculature; Radiation therapy; Vascular disruption.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiography / methods*
  • Animals
  • Contrast Media*
  • Female
  • Image Enhancement
  • Imaging, Three-Dimensional*
  • Metal Nanoparticles*
  • Mice
  • Microbubbles*
  • Microvessels / diagnostic imaging*
  • Neoplasms / blood supply*
  • Neoplasms / diagnostic imaging*
  • Ultrasonography / methods


  • Contrast Media