Sonobiopsy for sensitive and spatially targeted molecular diagnosis through integrating ultrasound with liquid biopsy

Abstract

Sonobiopsy uses focused ultrasound to enrich circulating biomarkers from ultrasound-targeted disease regions, enabling sensitive and spatially targeted molecular diagnosis through liquid biopsy. Since the concept of integrating ultrasound with liquid biopsy was introduced in 2009, the field has advanced to incorporate various ultrasound modalities for applications across a range of diseases. To drive clinical translation of sonobiopsy, it is essential to optimize focused ultrasound techniques, enhance biomarker analysis, and elucidate underlying mechanisms.

Keywords: Biological physics; Ultrasound.

Fig. 1. Illustration of sonobiopsy in preclinical and clinical applications.

The potential of sonobiopsy to enrich circulating biomarkers was demonstrated in preclinical disease models of colon cancer, prostate cancer, fibrosarcoma, brain transgene expression, heart transplant rejection, as well as in patients with brain tumors, Alzheimer’s disease, and uterine fibroids (The figure was generated using BioRender https://www.biorender.com).

Fig. 2. Milestones in the development of sonobiopsy.

In 2009, the concept of using ultrasound to amplify and localize circulating biomarkers was introduced. Since then, various FUS modalities have been used to enrich circulating biomarkers for cancers outside of the brain. In 2018, our group utilized FUS with microbubbles to enhance the release of brain cancer-derived biomarkers into the bloodstream. This technique has since progressed from studies in animal models to clinical applications in patients with brain tumors and Alzheimer’s disease. Lately, the application of sonobiopsy has been expanded to monitor brain transgene expression and heart transplant rejection.