Focused ultrasound in neurosurgery: a historical perspective

Abstract

<jats:p>Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.</jats:p>

Focused Ultrasound for Neuromodulation

“…There are many challenges to characterize the effects of ultrasound on the nervous system, including nonstationarity, limitations of translation across animal species, and, most obviously, the barrier of the skull. In contrast to the soft and relatively homogenous structure of the brain, the skull has a high acoustic impedance, reflecting a substantial portion of incident ultrasound waves, heating the overlying scalp, and distorting ultrasound through refraction [4]. The concave shape of the skull can naturally lens the remaining acoustic energy.…”

“…In particular, dual-mode ultrasound has enabled adaptive closed-loop approaches for correcting distortion from the skull through real-time iterative improvements in the appropriate weighting and timing of each transducer for certain applications [62,63]. In this way, the individual anatomy of a single patient or animal can be evaluated and accounted for as therapy is delivered in succession, precisely verifying the prescribed dose at the location within predetermined safety margins that may include specific tolerances at sensitive points in the ultrasound field [4]. Lastly, major advancements in three-dimensional stereotaxis have made multimodal investigations using magnetic resonance imaging and ultrasound possible through coregistration [64].…”

“…This characteristic fueled the development of diagnostic and therapeutic uses of ultrasound based on control over the interference of ultrasound waves. Arrays of ultrasound transducers spread physically apart can utilize constructive and destructive interference to concentrate energy at a single point [4]. Imaging or therapy using these beams of focused ultrasound is aptly named Bfocused ultrasound^(FUS).…”

The Emerging Role of Magnetic Resonance Imaging-Guided Focused Ultrasound in Functional Neurosurgery

“…Early studies have shown potential by introducing an oscillating microtubule contrast agent that, when pulsed via sonication, created a shearing stress that induced a reversible, spatially specific, increase in BBB permeability [25]. There have been several studies of MRgHIFU use in animals resulting in similarly increased BBB permeability for the delivery of chemotherapeutic agents, antibodies, and other neurotrophic factors into the CNS [39]. For example, a 13-to 14-fold increase in CNS chemotherapeutic drug concentrations after utilizing MRgHIFU to induce BBB-opening was discovered in rabbit models [25].…”

Magnetic Resonance-Guided Focused Ultrasound in Neurosurgery: Taking Lessons from the Past to Inform the Future

“…Ultrasound is a mechanical wave that occurs through a medium and propagates at frequencies higher than the range of human hearing of 20 Hz. 14 Basically, when ultrasound passes through a specific area, reflection and refraction occur at the boundary between two media with different acoustic impedances. 15 16 Specular reflection, which occurs when the acoustic rays contact a relatively smooth surface, usually contributes to delineate the interface between two soft tissues; therefore, displaying organ boundaries that could be used as diagnostic images.…”