Functional magnetic resonance imaging (fMRI) has become one of the leading research tools to study brain function and is playing a pivotal role in several large-scale brain mapping projects worldwide. Despite ongoing technical advancements in MRI which have greatly increased its availability and helped improve the resolution for functional brain mapping, we still have very limited understanding of what fMRI signals really represent. The fact that hemodynamic fMRI does not provide direct measurement of neuronal activities precludes many potential applications involving studies of neuronal circuit function. In contrast, electrophysiology detects actual electrical signaling with unsurpassed temporal and spatial resolution, but generally falls short of providing information in a large-scale network levl due to a limited number of recording sites. The desire to combine the strengths of both approaches prompted us to develop a high-resolution MR- compatible microelectrode array, permitting examination of electrophysiological signatures during MRI as well as evaluation of deep brain stimulation (DBS) efficacy using fMRI. Our pilot data have demonstrated success in using an advanced micromachining approach to fabricate a miniature electrode array with high-density electrodes (down to 75 m pitch). In contrast to many platinum-iridium, glass, and silicon-based electrodes, our microelectrode uses a flexible, highly biocompatible, and MR-compatible base substrate - polyimide, which is known to better match the mechanical impedance of the brain than the other materials commonly used. Our previous work has optimized the rigidity of our electrode by experimenting with various thicknesses and layer designs. This unique tool is extremely important to accommodate a variety of over-head MR coils and gradient inserts with small inner-diameters because the majority of the brain coils, particularly the ones for preclinical small animal systems, are too large to permit the placement of a percutaneous connector on the head. Additionally, the probe has a built in ribbon cable to the connector which can be placed few centimeters away from the MR radio-frequency (RF) coils, reducing the potential for RF-induced heating, voltage changes, and MR-related noise during electrophysiological recording. In this Phase 1 STTR award, we will quantitatively evaluate this novel microelectrode array in vivo using rat subjects, with Aim 1 studying ultra-high resolution DBS-fMRI, and Aim 2 developing/validating tools for simultaneous fMRI and electrophysiological recording. These studies will be crucial for the future success in commercializing the probe as it will generate preliminary data for marketing and also set the foundation for various types of applications to study neural circuits in normal and diseased brains. We believe our work will result in a highly unique product, opening up a new avenue to explore and validate functional connectivity in the brain with a resolution and scale that cannot be achieved by traditional fMRI or electrophysiology alone.

Public Health Relevance

Given the increasing use of magnetic resonance imaging (MRI) in brain research, understanding of what MRI signals really represent has become a fundamental yet fully elusive research topic. Recent neuroscience/neuroimaging research has also emphasized the importance of using multi-modal approaches, in which the data are acquired by multiple approaches so as to comprehensively interpret a specific neural event. Our project aims to bridge two of the most powerful and widely used research/clinical tools used in neuroscience - MRI and electrophysiology - by creating a novel MR-compatible 16-channel microelectrode array. The unique design of our tool allows the electrode shank to be bent to accommodate various insertion scenarios in the MRI environment while maintaining the stiffness required to penetrate brain tissue. This microelectrode array addresses two major applications: high resolution electrophysiology and deep brain stimulation. Both of which, in combination with simultaneous MRI, comprise a highly innovative platform which vastly improves our understanding of brain function and neural circuit connectivity.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
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Special Emphasis Panel (ZRG1)
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Grabb, Margaret C
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Blackrock Microsystems
Salt Lake City
United States
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Kao, Yu-Chieh Jill; Oyarzabal, Esteban A; Zhang, Hua et al. (2017) Role of Genetic Variation in Collateral Circulation in the Evolution of Acute Stroke: A Multimodal Magnetic Resonance Imaging Study. Stroke 48:754-761
Van Den Berge, Nathalie; Albaugh, Daniel L; Salzwedel, Andrew et al. (2017) Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI. Neuroimage 146:1050-1061