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Additional file 1: Figure S1. Weight registration, Weight (grams, y-axis) was regularly monitored to assess animal well-being over time (days, x-axis). Overall mice weight remained stable around the treatment day, indicated by a red dotted line. With increasing tumor growth, weight also decreased. Figure S2. BLI monitoring, BLI was measured twice a week for two weeks after treatment followed by once a week until humane endpoint was reached. For all mice, BLI signal did not decline after treatment, indicating tumor growth. Notably, in several cases BLI signal drastically dropped at humane endpoint. Dotted red line indicates time of treatment. Figure S3. Survival Analysis. Separated graphs from Figure 4 (Controls vs. Treatment). Day 0 is the start of treatment. “Days in experiment” represents the number of days after treatment. Figure 3A displays the survival curves of the control, vehicle FUS, and only FUS (p =0.2). Here, graphs overlap indicating no difference between the control groups. The same holds true for the treatment groups displayed in Figure 3B (survival curves of control, doxorubicin with FUS, and doxorubicin)(p = 0.7), 3C (control, Caelyx® with FUS, and Caelyx®)(p = 0.5) and 3D (control, 2B3-101 with FUS, and 2B3-101)(p = 0.9). Figure S4. Immunofluorescent (IF) staining on sagittal slices of mouse brains. A: IF of blood vessels (CD31 in red) and pegylated liposomes (anti-PEG in green) did not show the presence of liposomes 24 h after treatment except for mouse 1 and mouse 2 treated with Caelyx® and FUS. Yellow area indicates the tumor area. B: Enlarged picture shows the presence of Caelyx® liposomes in the cortex outside of the sonoporated area.

The treatment of breast cancer by MR guided HIFU has recently shown great potential for clinical practice. Although innovative lateral firing transducer designs allow to significantly reduce the risk of undesired tissue damage to the thoracic cage, the heart and the lung, such a design is typically limited by the aberration effect of the inhomogeneous tissue composition of the breast. This project proposes a correction strategy for this type of aberrations, based on high resolution MRI in conjunction with tissue ultrasound celerity measurements. The method is compatible with clinical practice and has the potential to lead to improved treatment efficiency and increased patient safety for MR guided HIFU ablations of breast cancer.