30.1 Introduction

Brain applications for high-intensity focused ultrasound (HIFU) were originally conceptualized and developed in the 1950s as an instrument to create discrete, precise lesions within the brain. ¹ , ² Widespread use of HIFU in the brain was hampered by high levels of energy dissipation at the skull, which resulted in heating of the scalp and cortical surface, and by competing noninvasive modalities such as radiosurgery.

Over the course of the past 20 years, there have been considerable technological advances allowing more efficient transcranial ultrasound delivery to the brain. Modern transcranial ultrasound transducers are arranged hemispherically with hundreds of individual ultrasound elements (▶Fig. 30.1). ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ A hemispherical configuration minimizes skull and soft-tissue heating by distributing acoustic energy over a large surface area. Second, a wave phase correction algorithm was developed to account for the variable thickness, density, and contour of the skull, making it possible to correct alterations in the acoustic wave while traveling through media with large discrepancies in acoustic impedance. ¹⁰

Among the first reported uses of modern transcranial ultrasound transducer systems for human brain ablations were medial thalamotomies for chronic neuropathic pain syndromes. Martin et al treated nine patients suffering from a wide array of therapy-resistant pain syndromes with bilateral centro-lateral thalamotomies with a mean initial pain relief of 68%. ¹¹ Jeanmonod et al later reported their longer-term outcomes with an average improvement in pain of 57% at 1 year. ¹² These initial studies led investigators around the world to seek additional applications for focused ultrasound (FUS) technology.

Following successful thalamic ablations for the treatment of chronic pain by Martin et al and Jeanmonod et al, three pilot studies were performed to assess the feasibility of using transcranial FUS Vim thalamotomy for the treatment of medication-refractory essential tremor. Elias et al reported a 75% improvement in hand tremor at 1 year as well as an 85% improvement in disability and a 66% improvement in quality of life, ¹³ and Lipsman et al reported 81% improvement in hand tremor at 3 months. ¹⁴ Chang et al reported similar improvements in tremor control among a cohort of 11 patients. ¹⁵

These three studies led to a randomized, double-blind control trial at eight international centers that included 76 patients. At 3 months, there was a 47% improvement in hand tremor and sustained 62% improvement in quality-of-life measures. ¹⁶ The results of this trial led to FDA approval of FUS for the treatment of essential tremor.

With recent technological advances, early success in pilot studies for tremor, and recent FDA approval, there is renewed interest in HIFU brain applications among neurosurgeons. Currently, ablative HIFU is being investigated as a treatment for Parkinson disease, psychiatric disorders, brain tumors, and a wide array of neurological diseases. ¹⁷ Studies consistently demonstrate submillimeter precision with this transcranial lesioning modality ¹² , ¹³ , ¹⁵ ; so, treatment for focal epilepsy and palliation of nonlocalized epilepsy would obviously be considered as a neurologic application. Despite encouraging laboratory and feasibility studies, there have been no published clinical trials thus far. In this chapter, we discussed some of the barriers in applying current FUS technology to the treatment of epilepsy, and several candidate epilepsy conditions for FUS treatment.

30.2 Barriers in Transcranial MR-Guided FUS for Epilepsy Treatments

The major limitation of transcranial FUS treatments continues to be transmitting enough energy through the skull. It is estimated that more than 90% of the delivered ultrasound energy is either reflected or absorbed by the skull. ¹⁸ Despite advancements in transducer design and skull correction algorithms, some patients enrolled in tremor trials have had failed treatments secondary to inadequate tissue heating at the acoustic focus.

Current transcranial FUS systems optimally deliver acoustic energy toward the geometric center of the skull where the most beams converge. Also, the acoustic focus of the currently FDA-approved midfrequency clinical system is discrete to within a few millimeters. In order to treat focal epilepsy lesions of different locations and sizes, these two factors will have to be considered in planning future clinical trials for epilepsy.

30.2.1 Therapeutic Envelope of Current Systems

As an ultrasound wave propagates from a medium of low density to another of higher density, an acoustic impedance mismatch causes a reflection, absorption, or distortion of energy at the interface of the two media. This phenomenon is especially important for transcranial ultrasound as there is a high mismatch between soft tissues of the scalp and the skull. Incident acoustic waves that are perpendicular to the impedance mismatch are more likely to propagate unimpeded. Thus, the multi-element, hemispherical transducer configuration not only disperses acoustic heating over a large surface area of the scalp but also promotes the likelihood that individual ultrasound elements will interact perpendicularly with the skull.

This configuration establishes the geometric center of the skull as the theoretical optimal target for the most efficient transcranial ultrasound delivery, while peripherally located targets closer to the skull would have less efficient delivery. As such, deeply located epileptic foci such as periventricular nodules or hypothalamic hamartoma are more ideally located for FUS targeting than superficially located lesions such as cortical dysplasia with current transcranial FUS systems (▶Fig. 30.2).

Although this presents a theoretical challenge for treating peripherally located epileptic lesions, there is little direct evidence that excludes these lesions. Furthermore, there are several individualized skull factors that can affect the efficiency of transcranial ultrasound delivery, which could allow for adequate tissue heating of lesions near the skull.

A second consideration regarding the skull and its heating are far-field effects of ultrasound especially regarding targets near the skull base. In a laboratory study, Monteith et al studied skull base heating during modeled treatments for trigeminal neuralgia. Significant heating of the skull base was observed, particularly near the internal auditory canal and adjacent cranial nerves. ¹⁹ The authors also found that this could be largely mitigated with careful masking of ultrasound elements analogous to shielding with radiosurgical treatments. ¹⁹ This study highlights the importance of far-field ultrasound effects on the skull base and its structures—a factor that will be important for treating the mesial temporal lobe. As the number of transcranial FUS treatments increases, there will be a better understanding of transcranial sonications and refinement of skull simulation algorithms that may allow for further efficiency and safety.

Related posts:

29 Radiosurgery for Medically Refractory Epilepsy 1 Collaborative Planning in Epilepsy Surgery 8 Parahippocampectomy: A New Surgical Technique for Temporal Lobe Epilepsy 17 Motor, Sensory, and Language Mapping in Epilepsy Surgery 22 Functional Hemispherectomy and Peri-insular Hemispherotomy 13 Surgery of the Insula

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