The ability of ultrasonography to safely penetrate deeply into the brain has made it an attractive technology for neurological applications for almost 1 century. Having recognized that converging ultrasound waves could deliver high levels of energy to a target and spare the overlying and surrounding brain, early applications used craniotomies to allow transducers to contact the brain or dural surface. The development of transducer arrays that could permit the transit of sufficient numbers of ultrasound waves to deliver high energies to a target, even with the loss of energy from the skull, has now resulted in clinical systems that can permit noninvasive focused ultrasound procedures that leave the skull intact. Another major milestone in the field was the marriage of focused ultrasonography with magnetic resonance thermometry. This provides real-time feedback regarding the level and location of brain tissue heating, allowing for precise elevation of temperatures within a desired target to lead to focal therapeutic lesions. The major clinical use of this technology, at present, has been limited to treatment of refractory essential tremor and parkinsonian tremor, although the first study of this approach had targeted sensory thalamus for refractory pain, and new targets and disease indications are under study. Finally, focused ultrasonography can also be used at a lower frequency and energy level when combined with intravenous microbubbles to create cavitations, which will open the blood-brain barrier rather than ablate tissue. In the present review, we have discussed the historical and scientific foundations and current clinical applications of magnetic resonance-guided focused ultrasonography and the genesis and background that led to the use of this technique for focal blood-brain barrier disruption.
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