Figure 2.

Example acoustic emission obtained during a volumetric sonication with closed-loop feedback control. (a,b) Example spectra obtained during individual bursts during sonications with and without microbubbles (MB) for the two passive cavitation detectors. Spectra obtained early in the sonication before the microbubbles arrived the brain were similar to those obtained in prior sonications performed without microbubbles. With microbubbles, large and obvious enhancement at the second and third harmonics was observed (a), while subharmonic emission was unchanged (b). Data are shown in dB relative to the noise floor obtained before the sonication started. (c) Spectrogram obtained during this sonication. Here, the data is shown in dB relative to the mean spectra of the first 8 seconds during the sonication with microbubbles. Normalizing the data to spectra obtained before the microbubbles arrived in the brain removed everything except for the harmonic emissions, highlighting the unique signals produced by the microbubbles in the ultrasound field. (d) Magnitude of the harmonic, subharmonic, and wideband (WB) emissions plotted as a function of time during the 9 locations targeted in a volumetric sonication. The magnitude of the harmonic emissions were similar for the 9 locations, and all achieved the controller goal of 6–7.5 dB above the noise floor (blue region). Some overshoot occurred. Only small changes were observed in the subharmonic emissions, and no wideband emissions were detected. (e) Acoustic power level as a function of time for the 9 locations. During the control period (green region), the power at each location was modified based on the magnitude of the harmonic emissions. After this time, the power level was fixed to the average value of all the bursts that were within the controller goal. In cases where subharmonic or wideband emissions above the noise floor were detected, the power level was reduced by 40% and fixed for the remainder of the sonication.