Focused ultrasound a new evidence of modulation of neurotransmitters in cns
This presentation is the property of its rightful owner.
Sponsored Links
1 / 12

Focused Ultrasound: a New Evidence of Modulation of Neurotransmitters in CNS PowerPoint PPT Presentation


  • 93 Views
  • Uploaded on
  • Presentation posted in: General

Focused Ultrasound: a New Evidence of Modulation of Neurotransmitters in CNS. Seung-Schik Yoo, Ph.D., M.B.A. Tissue Imaging/Engineering Laboratory Dept. of Radiology, Brigham and Women’s Hospital, Harvard Medical School (USA). Non-invasive Direct Neuromodulation. 1. 2. 3.

Download Presentation

Focused Ultrasound: a New Evidence of Modulation of Neurotransmitters in CNS

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Focused ultrasound a new evidence of modulation of neurotransmitters in cns

Focused Ultrasound: a New Evidence of Modulation of Neurotransmitters in CNS

Seung-Schik Yoo, Ph.D., M.B.A.

Tissue Imaging/Engineering Laboratory

Dept. of Radiology, Brigham and Women’s Hospital,

Harvard Medical School (USA)


Non invasive direct neuromodulation

Non-invasive Direct Neuromodulation

1

2

3

  • Needed for the assessment of region-specific brain function

    • A new modality for functional brain mapping, including the evaluation of white matter connectivity.

  • Needed for the modification and control of brain function

    • Control of aberrant brain activities in neural circuitries

    • High-impact, potential therapeutic applications covering wide spectrum of neurological and psychiatric disorders.

      Limitations of current neuromodulation technique

    • ECT,DBS,EpCS: Invasive

    • tDCS, TMS: Lack spatial specificity and have limited depth penetration

ECT

tDCS

DBS

EpCS

TMS

Adapted from Hoy and Fitzgerald, Nature Review/Neurology, 2010


Attempted neuromodulation via ultrasound

‘Attempted’ Neuromodulation via Ultrasound

  • Fry et al. (1958): Discovery of reversible neural suppression by focused ultrasound in cats

  • Gavrilov (1970’s-1980’s): Creation of neural sensation via FUS in humans

  • Magee (1993): Accidental discovery of auditory sensation during transcranial Doppler exam

  • Bachtold (1998): Reversible modulation of activity in ex vivo rodent brain tissue.

    But..…

  • Lacked systematic/modern approach

  • Lacked adequate hardware for the focused ultrasound

  • Use of mixed bands of frequencies, which are not optimized for the transcranial use.

Gavrilov, et al. 1985


Idea pulsed fus

Idea: Pulsed FUS

  • FUS can deliver acoustic energy to small and steerable regions of the brain (e.g HIFU for thermal ablative therapy of tumor).

    • Transcranial application < 1 MHz

    • Pressure waves are focused to small spot

  • Use only mechanical energy

    • Heat is not desired for safety reasons.

    • Pulsating acoustic pressure can alter the excitability

      in neurons.

  • Proposed method: Instead of continuous application of HIFU, apply the low intensityFUS stimulation as a train of pulses with sufficient inter-pulse intervals.

Ultrasound transducer

Acoustic Focus


Hardware single fus transducer

Hardware: Single FUS Transducer

  • Human applicator with image-guided tracking

  • Dual-channel, collimated ultrasound applicator for animal

IR Marker

Transducer

Transducer

Laser guide

Motion camera


Hardware software

Hardware/Software

  • Software

  • MRI-CT guided 3D Visualization

  • Ability to track head motion

  • Automatic data logging and archive

  • Integrated sonication control panel

  • Hardware

  • SonomoTM: Commercially-available

  • FUS unit + image-guidance unit

  • Base on a commercial IR optical tracking device (NDI, Canada)


Changes in extracellular neurotransmitters

Changes in Extracellular Neurotransmitters

  • Suppressive sonication (TBD=0.5msec, PRF=100Hz, Ispta=130mW/cm2) was delivered to the thalamus.

  • Microdialysis was performed to sample GABA, glutamate, dopamine, and serotonin from the frontal lobe.

  • Samples were collected every 20 minutes through the circulation of artificial CSF.


Modulation of ec neurotransmitters

Modulation of Ec Neurotransmitters

  • No change in Ec Glutamate

  • Decreased Ec GABA: Increased up-take of GABA ?

  • Increased Ec Dopamine: Potential facilitation of DA release?

  • Increased Ec Serotonin: Potential inhibition of 5HT re-uptake?

Glutamate

GABA

Dopamine

5HT


Expedited recovery from the anesthesia

Expedited Recovery from the Anesthesia

  • Excitatory FUS was given to the thalamus of the rats

  • Shortened the ketamine/xylazine anesthesia time

  • DBS to the intrathalamic nuclei (human) improved the awareness of the minimally-conscious state (MCS) patients

  • Potential application toward the consciousness


Potential mechanism

Potential Mechanism?

  • Not temperature-related

    • e.g. MR thermometry shows no temperature change.

  • Not electro-magnetic (Eddy currents related)

    • e.g. observed regardless of the MR environment

  • Most likely, mechanical

    • FUS induces microscopic vibration

    • Mediates mechanoreceptor

    • Induces Ion channel operation

Ultrasound Sonication

Further neuro-modulation

via plasticity

And more…

Changes in

Excitability &

Neuro-transmission

Neuronal membrane


Summary

Summary

1

2

3

4

Focused ultrasound can provide a new means for non-invasive, localized functional neuro-modulation.

Bi-modal modes of modulation, i.e. excitation and suppression, are possible.

FUS also changes the level of neurotransmitters, with potential implication in the treatment of psychiatric disorders.

Future works

  • Assessment of different FUS frequency and parameters

  • Larger animal testing including the primates

  • Assessment of session-specific/accumulative effects

  • Assessment of neuromodulatory role in PNS, which may have impact on pain management


Acknowledgement

Acknowledgement

  • Gerald J and Dorothy R Friedman Foundation

  • Focused Ultrasound Foundation

  • NARSAD

  • Center for Integration of Medicine and Innovative Technology

  • Incheon Saint Mary’s Research Grant

  • NIH National Center for Research Resources & NIH grant K24 RR018875 (to A. Pascual-Leone)

  • Byoung-kyong Min, Ph.D., Yongzhi Zhang, M.D., Krisztina Fischer, M.D., Ph.D., Nathan McDannold, Ph.D. (BWH), Kwang-ik Jung (Hallyn Univ)

  • Alvaro Pascual-Leone (BIDMC), Felipe Fregni (SRH)

  • Yongan Chung, M.D., Iso Maeng, M.D. (Incheon Saint Mary)

  • Emmanuel Filandrianos and Javig Taghahos (Boston Univ)


  • Login