Medical Imaging and Focused Ultrasound Treatment for Breast Tumors Using Harmonic Motion Imaging (HMI)

The objectives of this study are to demonstrate the initial clinical feasibility of using Harmonic Motion Imaging (HMI) for guiding and monitoring 1) Focused Ultrasound Surgery (FUS) in patients with benign tumors and stage 1 non-metastatic breast cancers and 2) microbubble-mediated Low Intensity Focused Ultrasound (LIFU), i.e., sonoporation, in early-stage, non-metastatic breast cancer patients. The secondary objective is to investigate the correlation between HMI-informed treatment response with patients' post-treatment immune profile. FUS is a non-invasive, non-ionizing treatment procedure that precisely focuses and delivers a large amount of ultrasound energy to the target area, causing a localized temperature rise and cell necrosis at the target. Patients with small solid tumors without positive lymph nodes have the highest survival rate. However, especially for patients with benign tumors (most common in younger women) and older patients (\>65 years old) who fit these criteria, an alternative treatment technique that is far less invasive than the current surgical or invasive ablative intervention may be more beneficial. The main advantage of treating breast tumors with focused ultrasound ablation (FUS) is its noninvasiveness, i.e., no need for surgery. Without surgery, recovery from the procedure is much faster, patients may experience less pain, and cosmetic results may be improved. On the other hand, microbubbles have been approved for use by the FDA in contrast-enhanced ultrasound imaging, e.g., cardiac and liver imaging. Research has shown that microbubble mediated LIFU can improve intratumoral drug uptake via a phenomenon termed sonoporation, as a result of cavitation of microbubbles. Sonoporation does not cause any unexpected bias or additional toxicity compared with chemotherapy alone. Currently, sonoporation lacks imaging guidance. In this study, HMI and contrast-enhanced power Doppler will be investigated to guide and monitor sonoporation. Microbubbles will be injected at an FDA-approved dose and route. HMI is an ultrasound elasticity method that can provide measurements of the locally generated mechanical response and inherent mechanical properties of tissues. The result is a new image that contains unique localized information on the relative stiffness in and around the tumor. HMI can be performed simultaneously with HIFU ablation so that HIFU ablation can be monitored with HMI without interruption of HIFU treatment. When used for monitoring thermal ablation using FUS, the integrated system is referred to as HMIgFUS, which stands for Harmonic Motion Imaging for Focused Ultrasound. The resulting synchronous monitoring system has the ability to follow and identify the areas of necrosis. This study aims to evaluate the HMI technique for monitoring FUS ablation in a clinical setting and investigate the correlation between HMI-monitored displacement and patients' immune response.