Figure 3.

Controlled Dox release from TSL-Dox with Closed-loop MRgFUS hyperthermia leads to improved Dox delivery in GL261 mice brain tumors. (A) Schematic of the experimental protocol. (B) Thermometry image fused over MRI T₂ image. (C) Temperature profiles of bistate closed-loop controller (low/high) from hyperthermia experiment demonstrating that all the MRgFUS treated mice reached the desired threshold for the duration of applied thermal stress for ~10 min. The experimentally determined controller temperature profiles were also in agreement with numerical simulations (41.5 ± 0.5 and 42.2 ± 0.4 °C). (D) Fluorometry comparison of remaining Dox in the blood after treatments, supporting that the employed protocol led to significant dox release (p ≤ 0.005, 6 mice per group). (E) Stained images of Dox, CD31, DAPI, and merged (No heat - left panel vs. Heat - right panel). (F) Quantification of the average fluorescence intensities between different treatment groups (p ≤ 0.001). The number of mice used per group was 4.