Detection of tumor stiffness and vasculature changes using Harmonic Motion Imaging and Ultrasound Localization Microscopy following contrast-enhanced-power-Doppler-guided sonoporation

Early-stage triple-negative breast cancer is an aggressive tumor type with neoadjuvant chemotherapy followed by surgery being the standard of care. Currently, only 30-60% of patients are able to achieve pathologic complete response that is associated with overall survival. Boosting treatment efficacy is therefore one of the key goals in the management of breast cancers. Microbubble-mediated focused ultrasound has been shown to improve drug delivery via stable cavitation-induced sonoporation. In this study, acute tumor responses, i.e., stiffness and perfusion changes, post sonoporation were characterized using Harmonic Motion Imaging (HMI) and Ultrasound Localization Microscopy (ULM). Besides, contrast-enhanced power Doppler was employed to guide sonoporation targeting of highly angiogenic regions. We have obtained 16% increase in median surrogate drug uptake compared to sham and found decreased tumor HMI displacement (3.2%), reduced vessel area (5.2%), and slightly increased flow speed (2.5%) in mice after sonoporation. For the first time, we have demonstrated that decrease in tumor perfusion and HMI displacements post sonoporation were highly correlated.