Focused ultrasound in the brain has recently been made possible by the advent of MRI monitoring and phased array transducers. The method is currently FDA-approved for ablation of the VIM for essential tremor, and BBB opening and neuromodulation are also being explored. In this talk I will review each of these applications and discuss how they drive the design of MR-guided FUS systems.
Though today ultrasound is mainly associated with imaging, therapeutic ultrasound actually precedes ultrasound imaging by a few decades, and was first tested for body applications back in the 1920s. In the 1950s the Fry brothers at U of Illinois worked on the first brain applications including ablation for movement disorders and neuromodulation. They used a four element system. After that though there wasn’t a lot of activity in the field of transcranial focused ultrasound (FUS), eventhough other body applications such as breaking kidney stones did continue to develop. And this was for two major reasons, first there was the lack of intraoperative guidance: what is the use of a non-invasive modality like FUS if you have to open up the skull to use it for anything? And then there was the challenge to deliver acoustic waves transcranially. The skull is highly absorptive of ultrasound so it heats up and prevents sound from penetrating into the brain, and at the same time it has a much higher speed of sound than soft tissue which creates phase aberrations so what little sound does make it through is defocused.
But then in the 1990s two technical developments converged to make brain FUS possible. The first was the development of low-frequency phased arrays, which enable more efficient acoustic transmission through the skull to the focal spot, since the user can tune the time delays on each of a thousand elements to make sure all the acoustic waves reach the intended focus at the same time. That is, the array could adapt to the subject’s skull. The lower the frequency the less the skull absorption, and so the current Insightec system used for ET runs at 650 kHz, and a newer system intended for targets outside the midbrain runs at 220 kHz. The second was MR imaging, including temperature imaging, which enables targeting and dosimetry without opening up the skull, the treatment is truly non invasive and so the value proposition started to make sense. Specifically, the transducer is built into a scan bed that conducts both degassed water and all the ultrasound generator signals to the transducer, and the whole thing is controlled from a PC sitting next to the scanner host PC outside the scan room.
Today, there are three major applications for FUS in the brain, each of which dictates different system designs. The first is ablation in which brain tissue is destroyed thermally, and ablation of the VIM for essential tremor is now FDA approved in the US. In this application, relatively short, high power sonications are applied to rapidly raise the tissue temperature with a very tight focus, but cavitation is avoided. The second is BBB opening using FUS and microbubbles, and the first clinical trials in using this for delivering therapeutic agents in the brain for Alzheimers are underway. In this application, a wider focus is tolerated to enable off-center brain steering, and cavitation is actually used to monitor treatment. The third emerging application is neuromodulation, in which low-pressure FUS is applied to inhibit or excite neurons, and both thermal rises and cavitation are to be avoided. In this talk, I will discuss these three applications and how they drive the design of systems specific to each.