Acoustic Molecular Imaging Beyond the Diffraction Limit In Vivo

Area of Science:

• Biomedical Engineering
• Medical Imaging
• Nanotechnology

Background:

• Ultrasound molecular imaging (USMI) noninvasively visualizes molecular markers in vivo using targeted microbubble contrast agents (MCAs).
• USMI is crucial for cancer research, aiding in predicting tumor malignancy and treatment response.
• Existing high-resolution ultrasound methods do not directly apply to molecular imaging.

Purpose of the Study:

• To demonstrate super-resolution visualization of biomarker expression in vivo using superharmonic ultrasound imaging (SpHI).
• To validate and optimize the SpHI method for molecular imaging applications.
• To create co-registered maps of biomarker expression and microvasculature in a preclinical cancer model.

Main Methods:

• Employed superharmonic ultrasound imaging (SpHI) with dual-frequency transducers and targeted contrast agents.
• Utilized localization microscopy processing for super-resolution reconstruction.
• Validated the technique in vitro using concurrent optical and ultrasound microscopy with a microvessel phantom, and performed in vivo experiments in a rat fibrosarcoma model.

Main Results:

• Achieved super-resolution visualization of biomarker expression in vivo.
• Demonstrated a resolution of 23 μm, a fivefold improvement over previous diffraction-limited molecular imaging.
• Generated co-registered maps of biomarker expression and microvasculature in a rat fibrosarcoma model.

Conclusions:

• Superharmonic ultrasound imaging (SpHI) enables super-resolution molecular imaging in vivo.
• The developed technique significantly enhances the resolution of molecular imaging, advancing preclinical and clinical cancer research.
• This method offers a powerful tool for detailed visualization of molecular targets and microvasculature.