Less prone to phase aberrations and absorption but may enhance cavitational effects

Transcranial HIFU research has recently paved the way for the development of complex, high cost and efficient methods requiring prior knowledge of the skull topology to perform accurate focusing with transcranial feasibility shown for ablation shown in humans. While HIFU therapy use continuous wave and relies on thermal effects in order to induce a thermal necrosis, ME-FUS BBB opening uses short pulsed-wave and relies mostly on mechanical effects such as cavitation. An alternative to correcting for the aberrations induced by the skull is to operate at lower frequencies, but the focus can become very wide due to diffraction effects, thus decreasing the spatial resolution. Sonothrombolysis studies use transcranial CW ultrasound to dissolve clots in the brain, at typically lower frequencies, which are less prone to phase aberrations and absorption but may enhance cavitational effects. The beam is generally loosely focused to cover a large volume of the brain in each application. However, one of these studies showed large, secondary hemorrhage, which has been hypothesized to be linked to unexpected enhanced cavitation effects caused by standing waves generated within the skull. Standing waves are known to be capable of trapping microbubbles in the antinodes and decreasing their inertial cavitation threshold. MEFUS BBB opening also relies on mechanical effects to transiently and Povidone iodine locally increase the trans-BBB permeability but uses PW sequences with very short duty Acipimox cycles. Therefore, the safety should be easier to ensure despite the use of low frequencies. Our group has thus selected a middle solution to the aforementioned tradeoff, i.e., operate at intermediate frequencies that allows transcranial propagation and sufficiently high spatial resolution with a single-element transducer, warranting a sufficiently wide safety window. Until now, feasibility with this system has been shown in simulations and in vitro. The BBB opening regions at the caudate and the hippocampus were shifted from the targeted location by respectively 0.6 mm and 0.9 mm laterally and 6.5 mm and 7.2 mm axially. T2-weighted MR sequences were also used to assess potential damages in the brain.

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