Focused Ultrasound Ablation for Neurological Disorders

Introduction

High-intensity focused ultrasound is a transformative technology for noninvasive therapeutic thermal ablation using ultrasonic waves. The response of the tissue varies depending on the energy delivery to the treatment area, ranging from transient inhibition to therapeutic ablation. In recent years, several technological advances have positioned focused ultrasound ablation (FUSA) as an emerging modality for transcranial surgery, particularly in the area of functional neurosurgery ( ). Initial investigations into the medical applications of ultrasounds began in the early 1940s ( ). In , Lynn et al. described the biological use of ultrasonic waves in animal tissue samples and in living animals. Initially, they recorded effects of low-, medium-, and high-intensity sound waves with varying exposure durations. Eventually, they transitioned testing to ex vivo tissue blocks and in vivo canine brains ( ). The authors successfully created microscopic lesions in different cortical regions. The clinical effects of FUSA persisted after reversal of anesthesia and were specific to location of ablation (e.g., paralysis, muscular coordination disturbance, and blindness). However, scalp necrosis remained a challenge in these experiments, underscoring the need of craniotomy for a potential human application.

Almost a decade later, performed a histologic analysis of nerve tissue exposed to focused ultrasound. Eventually, the Fry brothers were the first to create lesions using focused ultrasound in humans. Their experiments highlighted the different effects of focused ultrasound on gray and white matter; for example, nerve cell bodies were more susceptible to ultrasonic exposure than were nerve fibers. Those studies also showed that gray matter ablation required higher ultrasonic energy compared with white matter, theoretically due to higher blood flow in gray matter acting as a “heat sink.” By late 1950s, despite the successful application of focused ultrasound for movement disorders ( ), the procedure was largely abandoned due to the need for a craniotomy to allow ultrasound waves to reach the target. This limited the adoption of FUSA until the early 1990s, when advances in phase correction algorithms ( ) and implementation of magnetic resonance (MR) imaging (MRI) thermometry ( ) made transcranial procedures a reality. Today, MR-guided FUSA is an emerging noninvasive approach for the treatment of a variety of neurologic diseases (e.g., essential tremor [ET] and Parkinson disease [PD]) ( ) ( Fig. 31.1 ). It is an exciting technology for functional neurosurgery, especially with its precision, immediacy of clinical effects, and reversibility of effects at low sonication energy (presonication). The results of the first multicenter trials are encouraging ( ) and provide high expectations for its use in a variety of other neurologic disorders ( ). In this chapter, we briefly review the history of neurosurgical applications of ultrasound therapy, current clinical applications, and the emerging indications for FUSA. We also review the future advances in ultrasound technology for a wider application in neurologic disorders, including neuromodulation and blood–brain barrier (BBB) opening.

Initial Applications of Focused Ultrasound Ablation for Neurosurgery

Although initial medical use of focused ultrasound therapy ncluded improving wound healing and selective tissue destruction ( ), the Fry brothers were the front runners in testing FUSA in neurosurgery ( ). Their work led to advances in an ultrasound B-mode image-guided focused ultrasound system ( ), also called the “candy machine,” used specifically to treat brain tumors in the early 1970s. Meanwhile, Padmaker Lele was independently making significant advances toward clinical applications of focused ultrasound during the 1950s ( ). He used thermocouplers with focused ultrasound to deliver energy at the target and create more precise lesioning ( ). investigations, along with those of Dr. H Thomas Ballantine, led to other new discoveries and breakthroughs. Of importance, Ballantine et al. also envisioned opening of the BBB and attenuation of pain responses with FUSA ( ). Around the same time, in Sweden, Petter Lindstrom also pioneered the use of FUSA for neurosurgery ( ). He studied FUSA for pain, psychoneuroses, anxiety, depression, and epilepsy. He later introduced the idea to Lars Leksell ( ). Leksell was especially interested in focused ultrasound use in psychiatric disorders. His investigations for transcranial therapy met with technological challenges, leading him to redirect his focus to radiosurgery.

Hynynen et al. developed ultrasound transducers with phased arrays in an attempt to resolve the distortion issues of the ultrasound fields during transcranial treatments ( ). The phased arrays corrected for the phase deviations induced by the varied pathway lengths, permitting more-efficient focusing of the ultrasound beams. Later, focused ultrasound technology integration with MRI launched the modern era of FUSA for clinical neurosurgical applications. In the next section, we discuss the current clinical and research indications of FUSA.

Transcranial Focused Ultrasound Ablation for Neurosurgery