Modulating Nonlinear Acoustic Response of Phospholipid-Coated Microbubbles with pH for Ultrasound Imaging

Area of Science:

• Biomedical Engineering
• Ultrasound Imaging
• Nanotechnology

Background:

• Contrast-enhanced ultrasound (CEUS) is vital for deep tissue assessment.
• Tumor acidosis presents a diagnostic challenge in current imaging.
• Microbubble contrast agents (MBCAs) offer potential for advanced diagnostics.

Purpose of the Study:

• To investigate the effect of pH on microbubble (MB) echogenicity.
• To explore the potential of pH-activatable MBs for tumor acidosis detection.
• To characterize the mechanism of pH-mediated MB signal enhancement.

Main Methods:

• Utilized phosphatidylcholine microbubbles (PC-MBs) and a clinical ultrasound scanner.
• Monitored MB echogenicity and nonlinear echoes at neutral (pH 7.4) and acidic (pH 5.5) conditions.
• Employed B-mode and Cadence contrast pulse sequencing (CPS) harmonic imaging.

Main Results:

• Observed a 3-fold increase in harmonic signal intensity as pH decreased from 7.4 to 5.5.
• Demonstrated pH-mediated activation is tunable by phospholipid composition and requires phosphate groups.
• Hypothesized increased MB oscillation due to reduced interfacial tension at lower pH.

Conclusions:

• PC-MBs exhibit enhanced harmonic oscillation at acidic pH, mimicking tumor acidosis.
• This pH-dependent activation offers a novel mechanism for CEUS signal modulation.
• Findings suggest potential for developing smart ultrasound contrast agents for improved tumor imaging.