MR-Guided Focused Ultrasound-Stimulated Microbubble Radiation Enhancement Treatment for Breast Cancer: Exploratory Imaging Outcomes

Background: A Phase I trial to study the efficacy and safety of MR-guided FUS-MB (focused ultrasound–microbubble) treatment combined with radiotherapy (RT) using a fully electronically MRI-guided steerable focused ultrasound system was performed. The investigation here carried out an exploratory quantitative analysis of images for the first ten participants who were treated with MRgFUS-MB therapy, identifying texture-based MRI features that changed significantly after treatment and indicating probable treatment-related changes in tumour morphology. Methods and Findings: Ten patients with stage I-IV breast cancer (Age: 64 ± 10.8) underwent 2 FUS-MB therapies throughout their radiation treatments, as deemed appropriate by a multidisciplinary team. MRI scans were performed prior to treatment and at 1- and 3-month follow-up. The tumours were segmented, and 2D and 3D features, including shape, first-order and texture features, were extracted for original and wavelet-filtered T1-weighted fat-saturated MR images. The overall significance of radiomic features in association with morphological changes in the target tumour over 1-month and 3-month follow-up in comparison to the first treatment day was investigated. Results: The five most significant features (p < 0.05) were selected using a sample-related t-test, out of which most features were wavelet-filtered first-order features. First-order wavelet-filtered robust mean absolute deviation (RMAD) emerged as the most consistent significant feature for both 2D and 3D features with sampled grid spacings of 0.5 mm and 1 mm. The volume of the tumour demonstrated a decline for 80% of patients over 3 months, as measured by the 3D mesh volume of the tumour ROI. There was a significant decline in tumour size and image heterogeneity, indicating plausible changes in the tumour microenvironment possibly related to the treatment. Conclusions: Previous preclinical studies and clinical evaluations have demonstrated the efficacy of MR-guided FUS-MB therapy. MRI image-based features from the T1-weighted MR scans over various follow-up times provide potential evidence of changes in tumour tissue heterogeneity that might be treatment-related. MRgFUS MB therapy can possibly evolve as a mode of radiotherapy enhancement in the future, which warrants further controlled validation. The availability of adequate data in the future might possibly lead to the identification of image biomarkers related to treatment response, thus providing better clinical evaluations.