Contrast ultrasound imaging of the aorta does not affect progression of atherosclerosis or cardiovascular biomarkers in ApoE-/- Mice

Brendon W. Smith, Douglas G. Simpson, Sandhya Sarwate, Rita J. Miller, John W. Erdman, William D. O'Brien

Research output: Contribution to journalArticlepeer-review


Objectives-Ultrasound contrast agents (UCAs) enhance cardiovascular ultrasound imaging. Adverse biological effects have occurred after administration of UCAs, and more research is needed for a comprehensive understanding of the risks involved. We used the ApoE-/- mouse model of atherosclerosis to characterize the effects of ultrasound and UCAs on atherosclerosis and plasma biomarkers. Methods-Male ApoE-/- mice (8 weeks old; n = 24) were intravenously infused with a UCA (2 × 1010 Definity microbubbles per hour; Lantheus Medical Imaging, North Billerica, MA) and exposed to 2.8-MHz center frequency ultrasound (10 Hz pulse repetition frequency, 1.4 microseconds pulse duration, 2 minutes exposure duration, and 2 sites) at 1 of 3 derated peak rarefactional pressure amplitudes (0, 1.9, or 3.8 MPa), and then consumed either a chow or Western diet for 4 weeks (n = 4 per group). Blood plasma samples were collected before ultrasound exposure and at 2 and 4 weeks after exposure and assayed for total cholesterol and von Willebrand Factor (vWF). A pathologist measured atheroma thickness in formalin-fixed, hematoxylin-eosin-stained transverse aorta sections and scored them for severity of atherosclerosis. Results-Plasma total cholesterol initially averaged 286 mg/dL in the Western diet group and increased to 861 mg/dL after 4 weeks on the diet (P < .0001). Total cholesterol did not increase significantly in the chow diet group. Plasma vWF increased after 2 weeks on the Western diet (P < .0001). Atheroma thickness was greater in animals consuming the Western diet than in chow-fed animals (P < .05). Ultrasound had no significant effect on plasma total cholesterol, plasma vWF, or atheroma thickness. Conclusions-Contrast ultrasound did not increase the severity of atherosclerosis or alter cardiovascular biomarkers in the ApoE-/- mouse model.

Original languageEnglish (US)
Pages (from-to)1115-1122
Number of pages8
JournalJournal of Ultrasound in Medicine
Issue number6
StatePublished - Jun 1 2015


  • Atherosclerosis
  • Biomarkers
  • Cardiovascular disease
  • Contrast agents
  • Endothelium
  • Microbubbles
  • Ultrasound

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging


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