Researcher interview: Seung-Schik Yoo, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

Focused ultrasound researcher, Seung-Schik Yoo, PhD, is driven by a desire to help people with brain disorders. As leader of the Neuromodulation Working Group formed by the FUS Foundation’s Brain Program, he is collaborating with a multinational, multi-disciplinary team consisting of 27 specialists in neuroscience, physics, biomedical engineering and imaging. Their goal is to determine how pulsed, low intensity focused ultrasound can be used to assess region-specific brain functions and to modify and control aberrant brain activities.

The Working Group is now concentrating on advancing this approach as a tool for functional brain mapping and ideal target localization. Looking toward the future, Yoo foresees an even bigger use of FUS-mediated neuromodulation – the treatment of neurological conditions that range from epilepsy to psychiatric disorders, including chronic depression and substance abuse. 

Yoo, who works at Brigham and Women’s Hospital and is an Assistant Professor of Radiology at Harvard Medical School, has published preclinical research showing that the delivery of focused ultrasound-mediated neuromodulation to the cerebral cortex altered brain activity in a selective, reversible way. His experiments used FUS neuromodulation to both inhibit and stimulate motor activity in the brain. In the inhibitory mode, FUS suppressed epileptic seizure activity.

“Right now, we’re chasing after a temporary modulation because I think it is little too early to address the long-term efficacy of this approach,” Yoo observes. “Using this new tool to change the brain function, even temporarily, can lead into a long-term, positive change in the brain function. We call this plasticity in the brain.” Neuroplasticity, he explains, is a self-correcting mechanism that enables areas of the brain to restore balance and regain function.

Potential uses

When used to perform functional brain mapping, FUS-mediated modulation will provide clinicians with more precise veriification that they are targeting the right place in the brain before making a permanent lesion.  The first application could be in treating essential tremor. “This technique can be used in conjunction with existing focused ultrasound surgery to really confirm that the target – in this case, the specific thalamic nuclei – is the correct one to cure the essential tremor,” Yoo notes.

“Another application we are thinking about is the treatment of epilepsy. There are a lot of people who suffer from intractable epilepsy, and the current solution is to get a lobotomy, which is a very invasive type of surgery,” Yoo says. “We have found that focused ultrasound can suppress epileptic activities without having any drugs or without surgery. We hope, in the long term, this kind of technique will reduce seizures for the patient by taming and stabilizing aberrant brain areas.”

According to Yoo, the ultimate and largest application for FUS-mediated neuromodulation lies in the field of psychiatry. “Think about the number of people out there who suffer from drug misuse and from depression. We know where it’s coming from; it’s coming from aberrant brain activity patterns. This technology might be able to bring those people who are suffering from psychiatric disorders back to their normal life.”

Additional research is needed before this technique is developed to its full potential. For now, the Neuromodulation Working Group is focusing on advancing FUS-mediated functional brain mapping into human clinical trials. Toward this end, the group has created a research and development roadmap that identifies the final preclinical steps, which include determining neuromodulation parameters and demonstrating the safety of the technique.  

 “We are in dire need to move this technique to human clinical trials, even preclinical trials,” Yoo says. “We don’t believe technical issues are that much of a hurdle. I think we need more data that that has to be accumulated right before preclinical trials, and it requires more funding. The major obstacle is the need for more capital and more people. We definitely require more personnel and resources to bring this project to a successful conclusion.”

Related information:

Click here to read May 2010 newsletter article, Harvard’s Seung-Schik Yoo discusses research in FUS-mediated neuromodulation.

Nearly 80 leading scientists, researchers, public health officials and industry executives from 12 countries and 30 different institutions participated in the FUS Foundation’s third invitational Brain Workshop from October 23 to 26.

With 46 presentations on the agenda, this year’s workshop provided an in-depth progress report on the status of the Brain Program and the work ahead. As FUS Foundation Chairman Neal Kassell, MD told attendees, “Our primary interest is to rapidly advance the development and adoption of reimbursable applications that either fulfill an unmet clinical need or are significantly better than existing therapies in terms of outcomes, cost and convenience.”

In the spotlight at this year’s meeting was the essential tremor clinical trial at the University of Virginia. Spawned during the first Brain Workshop in 2009 and funded by the FUS Foundation, the 15-patient pilot study is nearing successful completion. It is considered a shining example of the fast-track progress that can be achieved by multi-disciplinary, collaborative working groups, which are a hallmark of the foundation’s Brain Program.  

This year’s Brain Workshop had three specific goals:

1. Produce a white paper documenting the state-of-the-art of MR-guided focused ultrasound and the brain. That document will be circulated to Brain Workshop participants and posted on the foundation’s website in December 2011.
    
2. Develop action plans for 2012-2013, including technical projects, preclinical studies, and clinical trials leading to reimbursable indications.
    
   • Essential Tremor – Develop a protocol for a multicenter, pivotal clinical trial that satisfies the requirements of the medical and scientific communities, the FDA and reimbursement organizations.
      
   • Parkinson’s Disease – Submit a pilot clinical trial protocol for FDA approval.
      
   • Brain Tumors – Develop new path forward to reach the goal of launching a pilot clinical trial for treating the whole intracranial volume. Keep plans for blood-brain barrier study on track.
      
   • Temporal Lobe Epilepsy – Continue preclinical investigation of feasibility and safety of treatment. Develop a dialog around a clinical treatment strategy for mesial temporal lobe epilepsy using focused ultrasound.
      
   • Ischemic Stroke – Rethink approach and chart a new direction that is beyond recanalizing a blocked artery. Investigate the use of unfocused ultrasound to treat the microcirculation in the ischemic region.
      
   • Intracerebral Hemorrhage – Draft a pilot clinical trial protocol while a preclinical study is being completed early next year.
      
3. Create a collaborative environment and infrastructure to facilitate achieving the above initiatives as rapidly as possible.

During the workshop, participants created new working groups to complete several technical projects, including:

Treatment envelope expansion for temporal lobe epilepsy, brain tumors, etc. – Effective and efficient treatment of brain tumors will require a much larger treatment envelope than currently provided by the InSightec ExAblate 650KHz brain system. The enlarged envelope will need to encompass the entire intracranial space, if possible.

Leader: JF Aubry, PhD (Institut Langevin); Working Group: Arik Hananel, MD (FUS Foundation), John Snell, PhD (FUS Foundation), Matthew Eames, PhD (FUS Foundation), Kullervo Hynynen, PhD (Sunnybrook), Thilo Hoelscher, MD (UCSD) and Ferenc Jolez, MD (Brigham & Women’s)
 

Controlled cavitation – For several applications, including blood-brain barrier opening and brain tumor ablation, bioeffects arising from cavitation become important. Hence, ways of robustly and safely detecting, characterizing and controlling cavitation will be investigated.

Leader: JF Aubry , PhD (Institut Langevin); Working Group: Thilo Hoelscher, MD (UCSD), Arne Voie, PhD (UCSD), Beat Werner, PhD (University Children’s Hospital, Zurich) plus representatives from InSightec and Brigham & Women’s Hospital
 

Acoustic Radiation Force Imaging (ARFI) – This technique will allow the position of the acoustic focus to be identified with very low energy and negligible heating. ARFI will be important for functional procedures, drug delivery, non-thermal ablation and clot lysis applications. It also looks to be a primary tool in the development of MR-based focusing schemes which promise to make pre-procedure CT unnecessary.

Leader: Mickael Tanter, PhD (Institut Langevin); Working Group: Kim Butts Pauley, PhD (Stanford), Nathan McDannold, PhD (Brigham & Women’s), Beat Werner, PhD (University Children’s Hospital, Zurich)
 

Volumetric thermometry – It is critically important to provide real-time, intraoperative thermal feedback during focused ultrasound procedures in the brain. This provides necessary safety monitoring and also verification of the targeted area. Currently, only a single plane through the target is monitored. This group is investigating ways of providing real-time thermal monitoring in three dimensions in order to allow better target verification and more comprehensive safety monitoring in and around the brain.

Leader: Dennis Parker, PhD (Utah); Working Group: Nathan McDannold, PhD (Brigham & Women’s) and Kim Butts Pauley, PhD (Stanford)
 

The next Brain Program update will occur next October during the foundation’s 2012 International Symposium on Focused Ultrasound Therapy. The next invitational Brain Workshop is tentatively scheduled for 2013.

Related information:

Brain Program overview
FUSF sponsors Landmark MRgFUS Brain Workshop (April 2009)
Brain Workshop Summary (July 2009)
FUS Foundation’s Brain Program is off to a strong start (May 2010)