Numerical prediction of frequency dependent 3D maps of mechanical index thresholds in ultrasonic brain therapy

Therapeutic ultrasound has been used in the brain for thrombolysis and high intensity focused ultrasound (HIFU) therapy. A low-frequency clinical study of sonothrombolysis, called the transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia (TRUMBI), has revealed an increased incidence of hemorrhage, which may have been caused by cavitation. The goal of this study is to determine if there is a comparable risk of generating cavitation during HIFU brain therapy at different frequencies.

Two approaches are used to transmit acoustic energy through the skull to the brain: low-frequency ultrasound, with a wavelength that is larger than the skull thickness, and high frequency ultrasound, that is sensitive to aberrations and must use corrective techniques. At high frequency, the mechanical index (MI) is lower, which translates to a higher cavitation threshold. In addition to the nonfocused geometry of the 300 kHz sonothrombolysis treatment device, two types of focused therapeutic transducers were modeled: a low frequency 220 kHz transducer and a 1 MHz transducer that required aberration correction with a time-reversal approach, representing the lowest and highest frequencies currently used. The acoustic field was modeled with a finite difference fullwave acoustic code developed for large scale computations, that is, capable of simulating the entire brain volume. Various MI thresholds and device geometries were considered to determine the regions of the brain that have an increased probability of cavitation events.

For an equivalent energy deposition rate, it is shown that at a low frequency there is a significant volume of the brain that is above the MI thresholds. At a high frequency, the volume is over 3 orders of magnitude smaller, and it is entirely confined to a compact focal spot.

The significant frequency dependence of the volumes with an increased probability of cavitation can be attributed to two factors: First, the volume encompassed by the focal region depends on the cube of the frequency. Second, the heat deposition increases with frequency. In conclusion, according to these simulations, the acoustic environment during HIFU brain therapy at 1 MHz is not conducive to a high probability of cavitation in extended regions of the brain.