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Nonthermal ablation of deep brain targets: A simulation study on a large
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Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is
currently limited to central brain targets because of heating and other beam
effects caused by the presence of the skull. Recently, it was shown that it is
possible to ablate tissues without depositing thermal energy by driving
intravenously administered microbubbles to inertial cavitation using
low-duty-cycle burst sonications. A recent study demonstrated that this ablation
method could ablate tissue volumes near the skull base in nonhuman primates
without thermally damaging the nearby bone. However, blood–brain disruption was
observed in the prefocal region, and in some cases, this region contained small
areas of tissue damage. The objective of this study was to analyze the
experimental model with simulations and to interpret the cause of these
The authors simulated prior experiments where nonthermal ablation was performed in
in anesthetized rhesus macaques using a 220 kHz clinical prototype transcranial
MRI-guided FUS system. Low-duty-cycle sonications were applied at deep
targets with the ultrasound contrast agent Definity. For simulations, a 3D
pseudospectral finite difference time domain tool was used. The effects of shear
mode conversion, focal steering, skull aberrations, nonlinear propagation, and the
presence of skull base on the pressure field were investigated using acoustic
wave propagation models.
The simulation results were in agreement with the experimental findings in the
prefocal region. In the postfocal region, however, side lobes were predicted by
the simulations, but no effects were evident in the experiments. The main beam was
not affected by the different simulated scenarios except for a shift of about 1 mm
in peak position due to skull aberrations. However, the authors observed
differences in the volume, amplitude, and distribution of the side lobes. In the
experiments, a single element passive cavitation detector was used to measure the
inertial cavitation threshold and to determine the pressure amplitude to
use for ablation. Simulations of the detector’s acoustic field suggest that its
maximum sensitivity was in the lower part of the main beam, which may have led to
excessive exposure levels in the experiments that may have contributed to damage
in the prefocal area.
Overall, these results suggest that case-specific full wave simulations
before the procedure can be useful to predict the focal and the prefocal side
lobes and the extent of the resulting bioeffects produced by nonthermal ablation.
Such simulations can also be used to optimally position passive cavitation detectors.
The disagreement between the simulations and the experiments in the postfocal
region may have been due to shielding of the ultrasound field due
to microbubble activity in the focal region. Future efforts
should include the effects of microbubble activity and vascularization on the
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