Ultrasound-mediated vascular remodeling in tumor and normal vessels

Yi-Ju Ho

Department of Biological Science and Technology, National Yang Ming Chiao Tung University 

Ultrasound provides widely applications in clinical diagnostic imaging and therapy because of its non-ionizing radiation, noninvasive, and portable features. Microbubble is one of the intravascular contrast agents for medical ultrasound imaging, which provides well information to diagnose tumors and cardiovascular diseases. The ultrasound wave is a kind of mechanical and pressure wave, which can activate the microbubble oscillation and produce additional mechanical forces from microstreaming, liquid jet, stable cavitation, and inertial cavitation. These acousto-mechanical effects stimulate adjacent cells to modulate cellular metabolism, vascular bioeffects, and tissue microenvironments. In addition, microbubbles can carry specific drugs, genes, or gases to be locally released at the targeted sites triggered by focused ultrasound for precision therapy. Acousto-mechanical oxygen therapy combining oxygen-loaded microbubbles and focused ultrasound can locally release oxygen and produce mechanical stimulation, which induces the vascular permeability enhancement, vasodilation, and reoxygenation in the vascular microenvironment. Enhanced blood perfusion promotes oxygen, nutrient and drug delivery to reduce hypoxic-induced drug resistance and inflammatory responses, resulting in improved therapeutic efficacy. Therefore, these ultrasound-mediated vascular remodeling mechanisms could be proposed as a potential strategy not only for tumor vascular normalization but also for ischemia-reperfused vessel repair.