title: Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation.
abstract: Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl2solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn2+. In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn2+ions, so that the system can release Mn2+ions rather than MnCl2solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high-resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based microelectrode arrays, the post-implantation DBS enables frequency-dependent MR imaging in vivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36 h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional neural interface engineering and controllable delivery technology, which can be utilized in more detailed exploration of the functional anatomy in the treatment of neurodegenerative diseases.
authors.affiliation: Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, P.O. Box 11010, 250 Wu-Xing Street, Taipei City, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Materials Science & Engineering, National Chiao Tung University, P.O. Box 30010, 1001 University Rd., Hsinchu, Taiwan.
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Lo
authors.affiliation: Department of Materials Science & Engineering, National Chiao Tung University, P.O. Box 30010, 1001 University Rd., Hsinchu, Taiwan.
authors.forename: Chao-Yi
authors.initials: CY
authors.lastname: Chu
authors.affiliation: Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University, No.866 Yuhangtang Rd., Hangzhou, Zhejiang Province 310058, China.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Lai
authors.affiliation: Department of Biomedical Engineering, National Yang Ming University, P.O. Box 11210, 155, Sec. 2, Linog St., Taipei, Taiwan. Electronic address: irradiance@so-net.net.tw.
authors.forename: You-Yin
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Materials Science & Engineering, National Chiao Tung University, P.O. Box 30010, 1001 University Rd., Hsinchu, Taiwan. Electronic address: sanyuanchen@mail.nctu.edu.tw.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D003287:Contrast Media / Q000008:administration & dosage; D046690:Deep Brain Stimulation / Q000295:instrumentation* / Q000379:methods; D004343:Drug Implants / Q000008:administration & dosage*; D004553:Electric Conductivity; D004567:Electrodes, Implanted; D004867:Equipment Design; D019544:Equipment Failure Analysis; D053783:Magnetic Resonance Imaging, Interventional / Q000295:instrumentation / Q000379:methods*; D008345:Manganese / Q000008:administration & dosage*; D046228:Microarray Analysis / Q000295:instrumentation; D008839:Microelectrodes; D000080385:Nanogels; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D025321:Surgery, Computer-Assisted / Q000379:methods
chemical_list: D003287:Contrast Media; D004343:Drug Implants; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D008345:Manganese; D011094:Polyethyleneimine
keywords: Controlled delivery; Deep brain stimulation; MEMRI; Nanogel; Neural interface