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Updated: Aug 26, 2026
In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography
Published on: February 16, 2016
Impact of myocardial contrast echocardiography on vascular permeability: comparison of three different contrast
Peng Li1, William F Armstrong, Douglas L Miller
1Department of Internal Medicine (Cardiology), University of Michigan, Ann Arbor, MI, USA.
Abstract:
Microvascular permeabilization, petechial hemorrhage and premature ventricular contractions (PVCs) have been demonstrated in an in vivo rat model of myocardial contrast echocardiography (MCE). The purpose of this study was to compare these effects for three US Food and Drug Administration (FDA)-approved ultrasound (US) contrast agents (US CA): Optison, Definity and Imagent. Evans blue dye, an indicator of microvascular permeability, and a contrast agent were injected IV in anesthetized rats suspended in a water bath to mimic scanning depths seen in clinical echocardiology. Diagnostic US B-mode scans with 1:4 end-systolic triggering were performed at 1.7 MHz using a cardiac phased-array scanhead to provide a short axis view of the left ventricle. To elicit readily measurable effects for comparisons, relatively high doses of the agent were used (50 to 500 microL kg(-1) for Optison, 25 to 200 microL kg(-1) for Imagent, 10 to 100 microL kg(-1) for Definity). Microvascular leakage was characterized by the area of Evans blue dye coloration on the hearts and by extraction of the dye from tissue samples. The number of petechia were counted on the epicardial surface of excised hearts. PVCs were counted from ECG traces recorded with the MCE images. Neither evidence of capillary leakage nor PVCs were seen in sham animals. Based on volume dose, Definity MCE produced more microvascular leakage, but there was no apparent difference between the three agents' microvascular damage potential, which increased linearly with dose at low doses, when expressed in terms of the number of stabilized microbubbles. Definity MCE resulted in fewer PVCs than the other agents. The effects increased strongly with peak rarefactional pressure amplitude, with apparent thresholds for petechiae at 0.4 MPa and for PVCs at about 1.0 MPa. These results should be of value for minimizing adverse potential in diagnosis and optimizing efficacy in therapeutic applications.
Insights
This study compared three ultrasound contrast agents in rats, finding Definity caused more microvascular leakage but fewer premature ventricular contractions. Dose and pressure influenced these adverse effects.
Area of Science:
- Cardiovascular Imaging
- Ultrasound Contrast Agents
- Microvascular Physiology
Background:
- Myocardial contrast echocardiography (MCE) can induce microvascular changes like leakage and arrhythmias.
- Three FDA-approved ultrasound contrast agents (Optison, Definity, Imagent) are widely used.
- Understanding agent-specific safety profiles is crucial for clinical application.
Purpose of the Study:
- To compare the in vivo effects of Optison, Definity, and Imagent on microvascular permeability and cardiac electrical activity.
- To evaluate dose-dependent adverse effects of these ultrasound contrast agents.
- To determine the influence of ultrasound pressure on observed effects.
Main Methods:
- Anesthetized rats underwent MCE using Evans blue dye to assess microvascular leakage.
- High doses of Optison, Definity, and Imagent were administered.
- Diagnostic ultrasound imaging and ECG recordings were used to quantify leakage, petechiae, and premature ventricular contractions (PVCs).
Main Results:
- Definity MCE showed increased microvascular leakage compared to Optison and Imagent on a volume dose basis.
- No significant difference in microvascular damage potential was observed between agents when normalized to microbubble count.
- Definity MCE resulted in fewer PVCs than the other agents; both petechiae and PVCs were pressure-dependent.
Conclusions:
- Ultrasound contrast agent dose and pressure amplitude significantly influence adverse effects like microvascular leakage and PVCs.
- Definity may have a more favorable safety profile regarding arrhythmias compared to Optison and Imagent.
- These findings are vital for optimizing the safe and effective use of ultrasound contrast agents in MCE.
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