Time-dependent size stability and shell behaviors of lipid-coated microbubbles

Area of Science:

• Biomedical Engineering
• Materials Science
• Acoustics

Background:

• Microbubbles are crucial ultrasound contrast agents.
• Ensuring long shelf life and stable size distribution is vital for microbubble efficacy.
• Understanding microbubble stability informs their application in medical imaging.

Purpose of the Study:

• To investigate the long-term stability and attenuation properties of a custom-made polydisperse microbubble suspension.
• To evaluate the impact of time on microbubble size, concentration, and shell characteristics.
• To provide data on the shelf life of lipid-coated microbubbles for ultrasound applications.

Main Methods:

• Microbubbles were prepared using mechanical agitation with a perfluorobutane (C4F10) gas core and a lipid mixture (DPPC:DPPE-PEG2000).
• Size distribution and attenuation were measured at regular intervals over 30 days.
• Shell properties were determined using the exponential elasticity model (EEM) applied to attenuation data.

Main Results:

• Microbubble size remained stable (∼2.25 μm) for 13 days, then slightly increased to ∼2.5 μm.
• Microbubble concentration decreased from 7.14 × 10^9 MB/mL to 3.29 × 10^9 MB/mL over 30 days, reducing attenuation.
• Shell elasticity and viscosity remained constant for 13 days, then increased by ~50% and ~200%, respectively.

Conclusions:

• The study provides valuable data on the in vitro shelf life and stability of lipid-coated microbubbles.
• Findings indicate a critical stability period of approximately 13 days for these microbubbles.
• The results inform the optimal usage and storage conditions for microbubbles as ultrasound contrast agents.