Delivery of Precision Acoustic Fields to Penetrating Neural Implants to Improve Longevity and Performance of the Neural Interface

Information

  • Research Project
  • 9726216
  • ApplicationId
    9726216
  • Core Project Number
    R21EB028055
  • Full Project Number
    1R21EB028055-01
  • Serial Number
    028055
  • FOA Number
    PAR-18-207
  • Sub Project Id
  • Project Start Date
    7/5/2019 - 4 years ago
  • Project End Date
    4/30/2021 - 3 years ago
  • Program Officer Name
    KING, RANDY LEE
  • Budget Start Date
    7/5/2019 - 4 years ago
  • Budget End Date
    4/30/2020 - 4 years ago
  • Fiscal Year
    2019
  • Support Year
    01
  • Suffix
  • Award Notice Date
    7/5/2019 - 4 years ago
Organizations

Delivery of Precision Acoustic Fields to Penetrating Neural Implants to Improve Longevity and Performance of the Neural Interface

This program evaluates the application of precision acoustic fields to penetrating neural implants to prevent electrode impedance rise and improve implant longevity. Problem to be solved: Chronic neural implants hold great potential for illuminating features of neural function and treating neurological disorders. Penetrating electrode arrays provide direct access to neural signals across the central and peripheral nervous system with high spatial resolution. A consistent point of failure for chronically implanted microelectrode arrays is the poor longevity and functionality of these devices, an issue that must be addressed to facilitate clinical translation of neural implant technology. One major failure mode of electrode arrays is the host tissue?s immune response (i.e., foreign body response or FBR), which causes glial scarring and neural cell loss near electrode sites, impairing recording quality. Efforts have been made to minimize the brain FBR through electrode design and pharmacological treatment, but there is no optimal solution; performance variability persists for all array types. We propose an innovative means of reducing the FBR by using low-intensity pulsed ultrasound to acoustically promote localized neurotrophic release in cortical tissue surrounding a neural implant. Studies will also focus on implanted transducers and provide new insights into the possible neuroprotective effects of frequencies above conventional transcranial ultrasound studies. Hypothesis. Application of localized ultrasonic fields of different acoustic parameters and treatment intervals can affect release of neurotrophic factors, and can be used to mitigate glial scarring, promote neural implant longevity, and neuron health. Aim 1 ? Design and characterize head-mounted ultrasound transducer for chronic in vivo studies. Acceptance Criteria: Acoustic stimulation is well-coupled and is thermally safe (<1°C temperature increase in tissue model). Aim 2 ? Identify ultrasonic parameters that safely stimulate acute neurotrophin release in cortical tissue below neural activation thresholds, in an in vivo model. Acceptance Criteria: Significantly increase neurotrophin release (e.g., BDNF) with low-intensity ultrasound stimulation, as measured through cerebral fluid sampling via an implanted microdialysis probe and tissue histology, without damaging neural tissue. Aim 3 ? Evaluate effects of low-intensity ultrasound stimulation on long-term neural electrode performance and glial scarring in cortical tissue in an in vivo model. Acceptance Criteria: Significantly (?=0.05) reduce the change in electrode impedance as compared to experimental control (no acoustic stimulation); significantly (?=0.05) improve neural recording quality (number of neural units, signal-to- noise ratios), over a 4-week period. Aim 4 ? Evaluate the effects of low-intensity ultrasound stimulation on the microglia response to a neural implant in an in vivo model. Acceptance Criteria: Significant reduction in microglia activation and migration within 200 µm of the electrode-tissue interface with periodic low-intensity ultrasound stimulation over a 4-week period.

IC Name
NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
  • Activity
    R21
  • Administering IC
    EB
  • Application Type
    1
  • Direct Cost Amount
    208373
  • Indirect Cost Amount
    120000
  • Total Cost
    328373
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    286
  • Ed Inst. Type
  • Funding ICs
    NIBIB:328373\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    BNVT
  • Study Section Name
    Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section
  • Organization Name
    ACTUATED MEDICAL, INC.
  • Organization Department
  • Organization DUNS
    791379030
  • Organization City
    BELLEFONTE
  • Organization State
    PA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    168238445
  • Organization District
    UNITED STATES