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Multi-timescale Microscopy Methods for the Characterization of Fluorescently-labeled Microbubbles for Ultrasound-Triggered Drug Release
Published on: June 12, 2021
In vivo study of microbubbles as an MR susceptibility contrast agent
Kelvin K Wong1, Ingjye Huang, Young R Kim
1Jockey Club MRI Engineering Center, University of Hong Kong.
Abstract:
The potential application of gas microbubbles as a unique intravascular susceptibility contrast agent for MRI has not been fully explored. In this study, the MR susceptibility effect of an ultrasound microbubble contrast agent, Optison, was studied with rat liver imaging at 7 T. Optison suspension in two different doses (0.15 mL/kg and 0.4 mL/kg) was injected into rats, and induced transverse relaxation rate increases (deltaR2*) of 29.1 +/- 1.6 s(-1) (N = 2) and 61.5 +/- 12.9 s(-1) (N = 6), respectively, in liver tissue. Liver uptake of intact albumin microbubbles was observed 10 min after injection. Eight of the 16 rats studied showed no susceptibility enhancement. This is probably attributable to the intravascular microbubble growth due to transmural CO2 supersaturation in the cecum and colon in small animals that causes microbubble aggregation and trapping in the inferior vena cava (IVC). In vitro deltaR2* measurements of Optison suspension at different concentrations are also reported.
Insights
Gas microbubbles show potential as MRI contrast agents. However, intravascular microbubble aggregation in rats limited their effectiveness, highlighting challenges for clinical translation.
Area of Science:
- Magnetic Resonance Imaging (MRI)
- Biomedical Engineering
- Pharmacology
Background:
- Gas microbubbles are being explored as intravascular susceptibility contrast agents for MRI.
- Their application remains limited due to challenges in controlling their behavior in vivo.
Purpose of the Study:
- To investigate the MR susceptibility effect of the ultrasound microbubble contrast agent, Optison, in rat liver imaging at 7 Tesla.
- To assess the dose-dependent effects and potential limitations of microbubble contrast agents.
Main Methods:
- In vivo MRI of rat livers at 7 T after intravenous injection of Optison at two different doses (0.15 mL/kg and 0.4 mL/kg).
- Measurement of induced transverse relaxation rate increases (deltaR2*).
- In vitro deltaR2* measurements of Optison suspension at various concentrations.
Main Results:
- Optison administration resulted in dose-dependent increases in liver deltaR2* (29.1 ± 1.6 s⁻¹ at 0.15 mL/kg, 61.5 ± 12.9 s⁻¹ at 0.4 mL/kg).
- Liver uptake of intact microbubbles was observed 10 minutes post-injection.
- Significant susceptibility enhancement was absent in 50% of rats, likely due to intravascular microbubble aggregation in the inferior vena cava.
Conclusions:
- Gas microbubbles, like Optison, can induce MR susceptibility effects in liver tissue.
- Microbubble aggregation and trapping in the inferior vena cava represent a significant challenge for their consistent application as intravascular MRI contrast agents in small animals.
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