Advance Technologies Center

High Intensity Focus Ultrasound mediated Neuro-Modulation

CNS (Central Nervous System) diseases require multi hospitalizations and long term care. Currently, most clinical options available for treatment are suboptimal; thus, the development of new therapeutic technologies is required. Applications for neuromodulation runs from Subdural and epidural cortical stimulation to deep brain stimulation (DBS), invasive methods that accompany inevitable risks. Other applications include Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation which are non invasive but are limited by their depth of penetration and their spatial specify. Therefore, Ultrasound, a non invasive method that can overcome these limitations can offer a better alternative. Focused Ultrasound (FUS), can noninvasively focus acoustic energy to specific locations in the brain and thus, create effects that can be exploited to develop new technologies for diagnostic and clinical application methods for a wide range of CNS disorders and diseases.

FUS has been studied for more than 50 years, specifically for its noninvasive potential ablation for brain tumors, epilepsy and movement disorders. Its technology development was delayed as a result of lack of proper imaging technologies and the need for craniotomy in order to allow efficient ultrasound entry into the brain (due to the skull irregular shape and thickness which results in high ultrasound absorption and heating of the skull bone). In the past years, the emergences of new technologies that allow safe and precise focus high-intensity beams have made FUS a realistic technology. FUS technology can be applied throughout the body, but its greatest potential lies in the brain and is attributed to its lack of invasiveness. FUS can be integrated with MRI which allows image-guided neuromodulation and thus, enable a better control of the process, such as energy deposition and focus guidance.

The primary goal of our research is to develop a technology enabling non-invasive and safe FUS-based reversible neuromodulation as an alternative treatment for Deep Brain Stimulation (DBS) technology. With recent advancements in the FUS technique, highly focused acoustic energy can be delivered to specific areas of biological tissues, as small as 1-2 millimeters in diameter. Ultrasound, typically operating at a frequency of

The potential of applying FUS to induce neuromodulation is still in initial stages and only very few studies have been published, suggesting its feasibility. Tufail et al (Tufail et al. 2010) first demonstrated in 2010 the feasibility of applying FUS for obtain neurostimulation in vivo, in a mouse model. Later on, Yoo et al (Yoo et al. 2011) demonstrated that FUS can modulate neural tissue excitability in the motor and visual cortices of rabbits. This feature has also been applied to decrease the electrographic seizure activities from chemically-induced epileptic rats (Min et al. 2011a), and to modify the extracelluar level of neurotransmitters (Min et al. 2011b; Yang et al. 2012) .These studies demonstrate the feasibility of applying FUS for inducing neuromodulation, thus confirming the motivation for this study.

Our research group has successfully achieved neurostimulation as well as neuroinhibitionin in rats undergoing FUS in a reproducible mode. These results encouraged us to focus on FUS as potential substitute/parallel technology for DBS for the treatment of various diseases such as Parkinson's disease (PD), pain, depression and other disorders.  Using FUS, we also intend to develop a functional/imaging tool for planning, guiding and monitoring FUS-induced neuromodulation. Our goal is to develop a methodology for calculating 3D Neuro-Modulation Maps (NMMs) which will depict/reflect the level of neuro-modulation induced by FUS with high resolution (1-2 mm). The NMMs will be used to significantly improve efficacy and applicability of deep brain stimulation (DBS) treatment for PD, pain, depression and other neurological and psychiatric disorders using focused ultrasound (FUS).In the future, this strategy will improve personalized treatment planning and will help to determine appropriate targets within these regions on a per patient basis.

Current and future  projects:

  1. Demonstrate feasibility for neuromodulation by FUS
  2. Study the feasibility of using FUS-based neuromodulation as a non-invasive treatment as an alternative treatment to DBS
  3. Demonstrate feasibility for non-invasive monitoring using MRI and NIRS
  4. Demonstrate the feasibility of producing FUS neuromodulation maps for DBS treatment planning (Pig Parkinson’s model)

Images:

FUS system:

 

FUS targeted at the motor cortex, thalamus and cerebellum regions

 

 

Project members-

    • Shirley Sharabi is a student of the direct root to PhD at Sackler school of  Medicine, Tel-Aviv University. the department of medical science. She is working on her thesis titled electroporation as a treatment for brain tumors at the Advanced Technology Center, Sheba Medical Center (Ramat Gan, Israel) since 2011.  She obtained a degree in physical therapy from Ben Guryon University in Beer-Sheva Israel and worked for several years as a physical therapist in the field of neurological rehabilitation.

    • David Last is a research fellow at the Advanced Technology Center, Sheba Medical Center (Ramat Gan, Israel) since 2006. He obtained an electrical and electronic engineering degree from the National Institute for Applied Sciences (Lyon, France) and a PhD in Electronics from the University Paris Sud (Orsay, France). He was a postdoctoral fellow at Beth Israel Deaconess Medical Center, Harvard Medical School (Boston, MA). His work is mainly focused on MRI, image processing and instrumentation.
    • David Guez obtained a PhD in Nuclear physics from the University Paris Sud (Orsay, France) and then worked for five years in development of nuclear imaging devices - three years in academic position in the field of nuclear medicine and two years as consultant in industry in charge of developing a prototype of neutron imager for homeland security application. He’s working since 2008 at the Sheba Medical center (Israel) as research fellow and is developing new MRI techniques for improved characterization of brain tumors.

    • Dana Berneman-Zeitouni, obtained her PhD in Human Genetics and Biochemistry from the school of Medicine, Tel-Aviv University.
      She's working since 2010 at the Sheba Medical center (Israel) as project manager, three years at the "Stem cell and regenerative medicine center" as a project manager, in the field of tissue replacement therapy for Type 1 diabetes. Since 2013 she is working as a project manager in the field of High Intensity Focus UltraSound mediated Neuro-modulation at the  neurosurgery department and the Advanced Technology Center, Sheba Medical Center (Ramat Gan, Israel).

    • DZion Zibly, neurosurgeon of the Department of Neurosurgery at Sheba Medical Center. After completion of medical School at the Technion, haifa, Dr Zibly completed the neurosurgery training program at Sheba Medical center followed by a couple of years of clinical and research fellowship at the National Institutes of Health, USA and in the Ohio State University in the field of functional stereotactic neurosurgery in the fields of DBS, PD and Pain therapy.

    • Sagi Harnof, attending neurosurgeon and Deputy chairman of the Department of Neurosurgery at Sheba Medical Center. After completion of medical School at TAU, Dr Harnof completed the neurosurgery training program at Sheba Medical Center followed by a two years clinical and research fellowship at the Department of Neurosurgery at the University of Virginia in the field of microsurgery and vascular surgery. Dr Harnof was part of the team that developed the tumor ablation application and was the leader of HIFU thrombolysis for stroke and ICH. Dr Harnof awarded the first fellowship position under his mentorship sponsored by the FUS foundation.

    • Yael Mardor, PhD, is the Chief Scientist and Head of the Magnetic Resonance Research Group at the Advanced Technology Center of the Sheba Medical Center. She is also a senior lecturer at Tel-Aviv University (TAU) Medical School. After completion of her PhD in Nuclear Physics at TAU in collaboration with Brookhaven National Lab, she proceeded to medical research with a focus on brain tumors and brain MRI. The Sheba setup, enabling pre-clinical/clinical research, close access to physicians/patients, and close collaboration with the industry, forms an optimal environment for translational medical research.