Exploring the possibilities

A special symposium at the EAN 2021 meeting explored the possibilities of navigated transcranial ultrasound for surgery, blood-brain barrier (BBB) opening, and neuromodulation. It could be a new frontier in neurotherapy.

Prof. Andres Lozano (University of Toronto, Canada) delivered a lecture on focused ultrasound energy across the skull as a novel, non-invasive method to make therapeutic lesions in the brain [1]. “Deep brain stimulation (DBS) is effective, and it would almost seem like a step backwards to make lesions in the brain,” Prof. Lozano noted. However, an important difference is that focused ultrasound is a non-invasive procedure, often done in an outpatient basis. “There is a general trend to use non-invasive therapy in outpatient neurosurgery. Some patients and physicians who are shunning surgery, will accept magnetic resonance-guided focused ultrasound. There is no delay in its effects, they are immediate.” In the eyes of Prof. Lozano, another important aspect of this technique is the harmonisation and blurring of boundaries between neurology, radiology, and neurosurgery. “I think there will be a new discipline of interventional neurology or interventional radiology, where perhaps neurologists and radiologists will work together with neurosurgeons to do these procedures. In some centres, neurologists are leading these efforts; in my personal belief, anyone with a proper training should be able to carry out these procedures.”

The first indication is tremor. Another possibility is lesioning the globus pallidus and subthalamic nucleus in addition to the thalamus to treat Parkinson’s disease. The anterior limb of the internal capsule, the subgenual cingulate, and other neuropsychiatric targets are also being considered to treat obsessive-compulsive disorder or depression, among others. In addition, several new indications are in development. “Particularly exciting are the possibilities to non-invasively treat epilepsy, trigeminal neuralgia, brain tumours, and maybe even dissolving blood clots.”

Prof. Jean-François Aubry (Physics for Medicine Paris, France) talked about focal BBB opening by focused ultrasound [2]. He said there is a need to safely and transiently open the BBB to enable drug delivery in the brain. This paves the way to more efficient drug therapies, such as chemotherapy for glioblastomas. He explained the principles and first results in humans of pioneering BBB opening with magnetic resonance guidance. The same clinical systems were used to induce thermal lesions, but at lower frequency (220 kHz) and in conjunction with intravenous injection of ultrasonic contrast (micro-bubble) agents. In a feasibility study, this was applied in 5 patients with high-grade glioma to deliver chemotherapy, in most cases temozolomide [3]. Focused ultrasound was also used to open the BBB in 5 patients with early-to-moderate Alzheimer’s disease (AD) in a phase 1 safety trial as a potential novel treatment and delivery strategy for AD patients [4]. Low-cost, lightweight handheld, and neuro-navigated systems specifically for BBB opening are now available. Prof. Aubry also said BBB opening can be used to deliver neuroactive drugs to modulate brain activity.

Focal neuromodulation with ultrasound transcranial pulse stimulation (TPS) was the third application of transcranial ultrasound that was discussed, by Prof. Roland Beisteiner (Medical University of Vienna, Austria) [5]. He said that highly focal brain stimulation and non-invasive DBS are feasible with modern ultrasound neuromodulation technologies. “These allow for unprecedented precision in targeting brain areas in pathological brains with altered connectivity.” Brain heating and generation of secondary stimulation maxima can be avoided with TPS. Clinical benefits of TPS are likely for all diseases which benefit from neuroplastic reorganisation (neurodegenerative diseases, psychiatric disorders). Secondly, benefits are likely for all diseases which rely on deep network nodes, since focused ultrasound allows for the first time for non-invasive DBS. Thirdly, TPS could be effective to treat diseases and conditions with focal pathologies which require precise targeting, most notably Parkinson’s disease, stroke, pain, and MS.

Data of the University of Vienna has shown:

• modulation of neuronal responses (SEP data);
• stimulation of neuroplastic reorganisation (fMRI data);
• reduction of cortical atrophy (MR data);
• improvement of brain performance in AD;
• motor improvements in Parkinson's disease, as shown by very recent clinical observations.

TPS data of application in over 2,000 patients have shown that ultrasound neuromodulation is safe.

1. Lozano A. Focal surgery with ultrasound. SYMP08-1, EAN 2021 Virtual Congress, 19–22 June.
2. Aubry JF. Focal blood brain barrier opening with ultrasound. SYMP08-2, EAN 2021 Virtual Congress, 19–22 June.
3. Mainprize T, et al. Sci Rep. 2019;9:321.
4. Lipsman N, et al. Nat Commun. 2018;9:2336.
5. Beisteiner R. Focal neuromodulation with ultrasound. SYMP08-3, EAN 2021 Virtual Congress, 19–22 June.

 

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Posted on 18 August 202118 August 2021