Get it Through Your Skull: Focused Ultrasound for ET

UPDATE: 6/10/2021
Originally published 3/7/2019

Since we posted the blog below, more information has been published on how skull thickness determines if an essential tremor (ET) patient qualifies for MRI-guided Focused Ultrasound (MRgFUS). As described in the original blog, it is a physics challenge to transmit ultrasound energy through solids, in this case, the cranium or skull bone. The goal is to maximize the efficiency of the ultrasound to produce destructive heat at the target without getting so hot that it damages neighboring tissue. How much energy to deliver is determined by the density (or thickness) of the cranium.

Therefore, before an ET patient can be assured their MRgFUS will be safe and effective, their skull density ratio (SDR) must be calculated. This is done using a cranium scan. An SDR score is determined. The lower the SDR, the more ultrasound energy is required to penetrate through bone to the target, and the standard threshold is a score of 0.40. How many patients actually meet this threshold?

The most recent statistic (as of this writing) is a 2021 study by Tsai, et al.[i] They evaluated the SDR of 246 tremor-dominant patients interested in receiving MRgFUS who enrolled in their study. Their ages ranged from 23-89 years old, and the group was made up of 162 males and 84 females. Out of the group, 114 had been diagnosed with ET, while the rest had other tremor types (e.g., Parkinson’s disease, psychogenic tremor, etc.)

Using the standard threshold, the authors found that roughly half of the patients qualified for MRgFUS based on their SDR. While this might seem on the low side, a multi-center study by Boutet, et al. (2019)[ii] suggests that scores below 0.40 may not necessarily exclude a patient from MRgFUS. In their study of 98 patients who has MRgFUS, 17 had a lower score, and required greater energy delivery which did not affect clinical outcomes. It is ultimately up to the neurosurgeon to evaluate each individual’s cranial thickness to determine the best probability that MRgFUS will be safe and successful.

 

Submarine movies can be gripping. They are particularly tense when the crew, trapped underwater in a silent-running sub, listens tensely to the enemy’s echo-locator from a surface battleship. “Ping … ping … ping … “They can run but not hide. The soundwaves bounce off the sub’s metal skin and are detected by the surface receiver. We understand why the crew is terrified, anticipating the imminent depth charges.

Echo-detection devices actually began with ocean use after the sinking of the Titanic in 1912. In 1915, “…physicist Paul Langevin was commissioned to invent a device that detected objects at the bottom of the sea. Laugevin invented a hydrophone – what the World Congress Ultrasound in Medical Education refers to as the ‘first transducer’.”iii

From echo-location to ultrasound

Nearly 30 years passed before the first efforts to beam “supersonic waves” into the body to detect unhealthy tissue. Austrian neurologist Karl Dussik is credited with developing the first apparatus to do so. Dr. Dussik reasoned, “Living cells are now colloidal systems, and most probably life and illness consist in a modification of these colloidal structures.”iv In other words, disease modifies healthy tissue, and supersonic waves—what we now call ultrasound—will pick up the structural differences. He experimented on himself by submerging all but his face in water (using the water as a medium for transmitting the sonic waves), then sending ultrasound waves through one side of his cranium (skull) to a receiver on the other side.

Dr. Dussik showed that the received waves could be transformed into electric energy and converted to photographic images. He became convinced that ultrasound could be used to detect brain tumors, similar to the way x-rays could detect tumors in lungs or other soft tissue. Of course, ultrasound has a definite advantage over x-rays. With no radiation exposure, it can be repeated as needed.

However, Dr. Dussik encountered a barrier to getting ultrasound information on the brain: the cranium itself. It is made of bone, not soft tissue, and this diminished the efficiency of ultrasound access to the brain. Fortunately, Dr. Dussik had a brother, Friederich, who was a physicist. Together, they worked on overcoming the problems posed by the cranium. “By 1947, the brothers had constructed ultrasonic equipment that was capable of producing images of intracranial [inside the cranium] regions that provided enough information to diagnose tumors.”v

Treating essential tremor with transcranial ultrasound

Then came the leap from using imaging ultrasound for diagnostic purposes to using focused ultrasound (FUS) to treat diseased tissue. By the new millennium, devices were in development that could generate multiple beams from different angles onto a targeted focus, where they create heat sufficient to destroy the target. Advanced imaging methods give FUS a great boost. In particular, Magnetic Resonance Imaging (MRI) allows accurate identification of the target, and provides a thermal tracking mechanism during treatment to assure effectiveness.

For essential tremor (ET), over 1,000 ultrasound “beams” are aimed at a tiny area of the brain’s thalamus called the VIM nucleus. This miniscule nucleus is a relay station that receives abnormal movement messages and forwards them ultimately to the hands, head or other body part where they result in tremors. The 1,000 beams that converge (meet) at the VIM nucleus interrupt the tremor signals by precisely destroying the “relay station” without harming neighboring brain tissue! Tremors stop, with minimal-to-no risk of side effects.

Getting FUS through the skull

“But wait!” you think. “What about the problem Dr. Dussik encountered in getting ultrasound through the skull’s bone?” Well, today’s FUS uses phased array transducers that enhance its ability to pass efficiently through difficult obstacles such as bone. In addition, “Clinicians can modulate the parameters of sonication in recent systems, including the intensity of acoustic energy and frequency and sonication time depending on the purpose of treatment and characteristics of the subject.”vi

As a precaution, those considering FUS to control their tremors have a pretreatment imaging scan to determine their skull density ratio (SDR). This ensures they are good candidates for the treatment. If so, they can look forward to the same experience of regaining quality of life as our ET patients at Sperling Neurosurgery Associates. For more information, visit our website.

i Tsai KW, Chen JC, Lai HC, Chang WC et al. The Distribution of Skull Score and Skull Density Ratio in Tremor Patients for MR-Guided Focused Ultrasound Thalamotomy. Front Neurosci. 2021 May 17;15:612940.
ii Boutet A, Gwun D, Gramer R, Ranjan M et al. The relevance of skull density ratio in selecting candidates for transcranial MR-guided focused ultrasound. J Neurosurg. 2019 May 3;132(6):1785-1791.
iii“The History of Ultrasound.” Diagnostic Medical Sonography. https://www.ultrasoundschoolsinfo.com/history/
ivhttp://www.ob-ultrasound.net/dussik_apparatus.html
vShampo MA, Kyle RA. “Karl Theodore Dussik – Pioneer in Ultrasound.” Mayo Clinic Proceedings. 1995 Dec.;70(12):1136. https://www.mayoclinicproceedings.org/article/S0025-6196(11)63437-X/abstract
viJung NY, Chang JW. Magnetic Resonance-Guided Focused Ultrasound in Neurosurgery: Taking Lessons from the Past to Inform the Future. J Korean Med Sci. 2018 Oct 4;33(44):e279. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200905/

About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Neurosurgery Associates.

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