Ultrasound and Microbubble Mediated Provascular Therapy Charaterized Using Ultrasound Localization Microscopy

Hypoxia is an important mechanism of resistance to radiotherapy. Previous work in the field has demonstrated that ultrasound targeted microbubble cavitation (UTMC) can induce a provascular response in tumors that improved radiotherapy (RT) efficacy. The increase in perfusion can be characterized by burst replenishment imaging (BRI), which is however limited in resolution. Therefore, to characterize the impact of UTMC on the microvasculature, we decided to combine BRI with ultrasound localization microscopy (ULM), allowing for a resolution of approximately 20 µm versus 500 µm for BRI. In this paper, we demonstrate the feasibility of this combined imaging in muscle. Our data supports that ULM can be used to quantify changes in perfusion caused by UTMC mediated provascular therapy with a sensitivity comparable to BRI.