Molecular Ultrasound Imaging, The study discusses a novel method for improving molecular ultrasound imaging of atherosclerosis using targeted microbubbles (MBs). The focus is on creating a triple-targeted microbubble (MBVIS) by integrating antibodies against vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) along with synthetic sialyl Lewis X (sLex) onto the surface of MBs. This design mimics the behavior of inflammatory leukocytes and enhances the adhesion of microbubbles to inflamed endothelial cells, improving the sensitivity of ultrasound molecular imaging for early-stage atherosclerosis detection.
Key Methods and Findings:
Development of Targeted Microbubbles:
- The microbubbles were engineered using biotin-avidin linkage, attaching the selected antibodies and sLex polymer to the surface of lipid-shelled microbubbles.
- These triple-targeted MBVIS showed enhanced adhesion to inflammatory endothelial cells in both static and dynamic flow conditions.
In Vivo Evaluation:
- In vivo experiments in ApoE-deficient mice with atherosclerosis showed that MBVIS significantly improved ultrasound imaging signals compared to single- and dual-targeted microbubbles.
- MBVIS successfully detected early atherosclerotic changes by showing reduced ultrasound signals in atorvastatin-treated mice, highlighting its potential for evaluating therapeutic efficacy.
Histology and Therapeutic Insights:
- Histological staining further supported the imaging results, showing reduced lipid deposition and improved endothelial function in atorvastatin-treated mice.
- The study shows ultrasound molecular imaging’s effectiveness in detecting atherosclerosis and assessing drug effects, like atorvastatin.
Conclusion:
The study highlights the potential of using triple-targeted microbubbles (MBVIS) in ultrasound molecular for the early diagnosis and therapeutic evaluation of atherosclerosis. This approach can enhance detection sensitivity and therapeutic monitoring, particularly when combined with existing treatments like atorvastatin. Additionally, it offers a promising method for improving early diagnosis and evaluating drug efficacy.
