Effect of Ultrasound Combined with Microbubbles on Blood Perfusion in Invasive Breast Cancer—A Prospective Clinical Trial

Introduction Blood perfusion insufficiency and hypoxia are the main causes of drug resistance to chemotherapy in breast cancer. Increasing blood perfusion can improve drug delivery. This study aimed to investigate the effects of ultrasound-stimulated microbubbles (USMBs) on hemoperfusion in invasive breast cancer (IBC). Methods In this prospective clinical trial, 36 patients diagnosed with IBC were enrolled sequentially. The treatment group (n = 18, enrolled from June 2022 to April 2025) were treated with SonoVue ® microbubbles (MBs) stimulated by ultrasound, with a mechanical index (MI) of 0.2–0.3: 1 mL of SonoVue ® MBs was injected at 3.5-min intervals three times for a USMB treatment lasting 10 min. The control group (n = 18, enrolled from May to November 2025) received identical MB injections without ultrasound stimulation. Contrast-enhanced ultrasound (CEUS) was used to evaluate the changes in blood perfusion. Results In the treatment group, in comparison with the pre-treatment findings, the tumor perfusion area expanded ( P < .001) and the time to peak (TTP) increased ( P < .05) after USMB treatment. For regions exhibiting low enhancement inside the lesion on CEUS before USMB treatment, the area under the curve (AUC) ( P < .001) and mean transit time (MTT) ( P < .05) both increased following therapy. In the control group, none of the parameters showed statistically significant differences after the MB injections. Conclusion USMB treatment can improve blood perfusion in IBC, especially by enhancing the AUC and MTT in hypoperfused regions. These findings highlight the potential of USMB treatment as a noninvasive technique to enhance intratumoral drug delivery, although further validation of this approach is required. Clinical trial registration number: NCT06158217.