Several problems challenge mesoscopic imaging in the brain: 1) Difficulty with positioning high-NA objectives near the brain; 2) Creating a flat imaging window against the surface of the brain; 3) Adjusting the imaging window in the face of changes in swelling and pressure in the brain; 4) Preventing growth of dura and biofilms that obscure the imaging window; 5) Follow-on MRI imaging of the animal post-implantation. We propose here an ultra-large window radiolucent implant to address these issues. Our approach provides a 2 cm diameter window for non-human primates (NHPs) that regulates pressure and employs a stable, strong, and thin design. The system is mechanically modeled and stress-tested to achieve access to the brain by large objectives, with design features that allow for manual repositioning of the imaging lens. To optimize the distance between the objective and the brain, we prioritize a thin implant design. A strong radiolucent implant is created using PEEK plastic, a strong, thermoresistant and biostable material. We heighten strength of the chamber’s attachment to the skull by using titanium screws that are normal to the surface of the bone at each point. The implant design has several parts and contemplates a potential method to maintain pressure on the brain. This method uses an engineered silicone mount to maintain even pressure of the imaging window on the brain’s surface, despite brain motion. The mechanical properties of the silicone are manipulated to closely resemble that of brain tissue to be more biomimetic and act as a cushion for motion. This method also allows for the manual repositioning of the cover slip to create a flat imaging window. Lastly, our approach prevents dural growth by blocking the migration of migratory biofilm-forming cells; we hypothesize that use of dynamic pressure maintenance on the brain is key to this method’s success. We are also investigating methods to elongate the longevity of the implant and imaging site, such as silver sputtering on implants and blue light therapy. These methods have produced an ultra-large field of view with 2P image results in <60,000 neurons. As such the chambers are expected to enhance recording window longevity and may prove to be a critical advance in NHP and human brain imaging.
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Clinical viability of magnetic bead implants in muscle
Human movement is accomplished through muscle contraction, yet there does not exist a portable system capable of monitoring muscle length changes in real time. To address this limitation, we previously introduced magnetomicrometry, a minimally-invasive tracking technique comprising two implanted magnetic beads in muscle and a magnetic field sensor array positioned on the body’s surface adjacent the implanted beads. The implant system comprises a pair of spherical magnetic beads, each with a first coating of nickel-copper-nickel and an outer coating of Parylene C. In parallel work, we demonstrate submillimeter accuracy of magnetic bead tracking for muscle contractions in an untethered freely-roaming avian model. Here, we address the clinical viability of magnetomicrometry. Using a specialized device to insert magnetic beads into muscle in avian and lagomorph models, we collect data to assess gait metrics, bead migration, and bead biocompatibility. For these animal models, we find no gait differences post-versus pre-implantation, and bead migration towards one another within muscle does not occur for initial bead separation distances greater than 3 cm. Further, using extensive biocompatibility testing, the implants are shown to be non-irritant, non-cytotoxic, non-allergenic, and non-irritating. Our cumulative results lend support for the viability of these magnetic bead implants for implantation in human muscle. We thus anticipate their imminent use in human-machine interfaces, such as in control of prostheses and exoskeletons and in closed-loop neuroprosthetics to aid recovery from neurological disorders.
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- Award ID(s):
- 1832795
- NSF-PAR ID:
- 10392374
- Date Published:
- Journal Name:
- Frontiers in Bioengineering and Biotechnology
- Volume:
- 10
- ISSN:
- 2296-4185
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Several problems challenge mesoscopic imaging in the brain: 1) Difficulty with positioning high-NA objectives near the brain; 2) Creating a flat imaging window against the surface of the brain; 3) Adjusting the imaging window in the face of changes in swelling and pressure in the brain; 4) Preventing growth of dura and biofilms that obscure the imaging window; 5) Follow-on MRI imaging of the animal post-implantation. We propose here an ultra-large window radiolucent implant to address these issues. Our approach provides a 2 cm diameter window for non-human primates (NHPs) that regulates pressure and employs a stable, strong, and thin design. The system is mechanically modeled and stress-tested to achieve access to the brain by large objectives, with design features that allow for manual repositioning of the imaging lens. To optimize the distance between the objective and the brain, we prioritize a thin implant design. A strong radiolucent implant is created using PEEK plastic, a strong, thermoresistant and biostable material. We heighten strength of the chamber’s attachment to the skull by using titanium screws that are normal to the surface of the bone at each point. The implant design has several parts and contemplates a potential method to maintain pressure on the brain. This method uses an engineered silicone mount to maintain even pressure of the imaging window on the brain’s surface, despite brain motion. The mechanical properties of the silicone are manipulated to closely resemble that of brain tissue to be more biomimetic and act as a cushion for motion. This method also allows for themanual repositioning of the cover slip to create a flat imaging window. Lastly, our approach prevents dural growth by blocking the migration of migratory biofilm-forming cells; we hypothesize that use of dynamic pressure maintenance on the brain is key to this method’s success. We are also investigating methods to elongate the longevity of the implant and imaging site, such as silver sputtering on implants and blue light therapy. These methods have produced an ultra-large field of view with 2P image results in <60,000 neurons. As such the chambers are expected to enhance recording window longevity and may prove to be a critical advance in NHP and human brain imaging.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fbioe.2022.1010276
