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      In-vitro Recordings of Neural Magnetic Activity From the Auditory Brainstem Using Color Centers in Diamond: A Simulation Study

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          Abstract

          Magnetometry based on nitrogen-vacancy (NV) centers in diamond is a novel technique capable of measuring magnetic fields with high sensitivity and high spatial resolution. With the further advancements of these sensors, they may open up novel approaches for the 2D imaging of neural signals in vitro. In the present study, we investigate the feasibility of NV-based imaging by numerically simulating the magnetic signal from the auditory pathway of a rodent brainstem slice (ventral cochlear nucleus, VCN, to the medial trapezoid body, MNTB) as stimulated by both electric and optic stimulation. The resulting signal from these two stimulation methods are evaluated and compared. A realistic pathway model was created based on published data of the neural morphologies and channel dynamics of the globular bushy cells in the VCN and their axonal projections to the principal cells in the MNTB. The pathway dynamics in response to optic and electric stimulation and the emitted magnetic fields were estimated using the cable equation. For simulating the optic stimulation, the light distribution in brain tissue was numerically estimated and used to model the optogenetic neural excitation based on a four state channelrhodopsin-2 (ChR2) model. The corresponding heating was also estimated, using the bio-heat equation and was found to be low (<2°C) even at excessively strong optic signals. A peak magnetic field strength of ∼0.5 and ∼0.1 nT was calculated from the auditory brainstem pathway after electrical and optical stimulation, respectively. By increasing the stimulating light intensity four-fold (far exceeding commonly used intensities) the peak magnetic signal strength only increased to 0.2 nT. Thus, while optogenetic stimulation would be favorable to avoid artefacts in the recordings, electric stimulation achieves higher peak fields. The present simulation study predicts that high-resolution magnetic imaging of the action potentials traveling along the auditory brainstem pathway will only be possible for next generation NV sensors. However, the existing sensors already have sufficient sensitivity to support the magnetic sensing of cumulated neural signals sampled from larger parts of the pathway, which might be a promising intermediate step toward further maturing this novel technology.

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          Going deeper than microscopy: the optical imaging frontier in biology.

          Optical microscopy has been a fundamental tool of biological discovery for more than three centuries, but its in vivo tissue imaging ability has been restricted by light scattering to superficial investigations, even when confocal or multiphoton methods are used. Recent advances in optical and optoacoustic (photoacoustic) imaging now allow imaging at depths and resolutions unprecedented for optical methods. These abilities are increasingly important to understand the dynamic interactions of cellular processes at different systems levels, a major challenge of postgenome biology. This Review discusses promising photonic methods that have the ability to visualize cellular and subcellular components in tissues across different penetration scales. The methods are classified into microscopic, mesoscopic and macroscopic approaches, according to the tissue depth at which they operate. Key characteristics associated with different imaging implementations are described and the potential of these technologies in biological applications is discussed.
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              Nitrogen-vacancy centers in diamond: nanoscale sensors for physics and biology.

              Crystal defects in diamond have emerged as unique objects for a variety of applications, both because they are very stable and because they have interesting optical properties. Embedded in nanocrystals, they can serve, for example, as robust single-photon sources or as fluorescent biomarkers of unlimited photostability and low cytotoxicity. The most fascinating aspect, however, is the ability of some crystal defects, most prominently the nitrogen-vacancy (NV) center, to locally detect and measure a number of physical quantities, such as magnetic and electric fields. This metrology capacity is based on the quantum mechanical interactions of the defect's spin state. In this review, we introduce the new and rapidly evolving field of nanoscale sensing based on single NV centers in diamond. We give a concise overview of the basic properties of diamond, from synthesis to electronic and magnetic properties of embedded NV centers. We describe in detail how single NV centers can be harnessed for nanoscale sensing, including the physical quantities that may be detected, expected sensitivities, and the most common measurement protocols. We conclude by highlighting a number of the diverse and exciting applications that may be enabled by these novel sensors, ranging from measurements of ion concentrations and membrane potentials to nanoscale thermometry and single-spin nuclear magnetic resonance.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                13 May 2021
                2021
                : 15
                : 643614
                Affiliations
                [1] 1Department of Health Technology, Technical University of Denmark , Kongens Lyngby, Denmark
                [2] 2Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark
                [3] 3Department of Physics, Technical University of Denmark , Kongens Lyngby, Denmark
                [4] 4Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre , Hvidovre, Denmark
                Author notes

                Edited by: Michele Giugliano, International School for Advanced Studies (SISSA), Italy

                Reviewed by: Patrick Degenaar, Newcastle University, United Kingdom; Joerg Wrachtrup, University of Stuttgart, Germany

                *Correspondence: Axel Thielscher, axelt@ 123456drcmr.dk

                These authors have contributed equally to this work

                This article was submitted to Neural Technology, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2021.643614
                8155532
                34054404
                60873914-c356-4b1c-b0b2-b5069d4f13a9
                Copyright © 2021 Karadas, Olsson, Winther Hansen, Perrier, Webb, Huck, Andersen and Thielscher.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 December 2020
                : 12 April 2021
                Page count
                Figures: 7, Tables: 0, Equations: 13, References: 74, Pages: 17, Words: 0
                Funding
                Funded by: Novo Nordisk Fonden 10.13039/501100009708
                Funded by: Innovationsfonden 10.13039/100012774
                Categories
                Neuroscience
                Original Research

                Neurosciences
                cable equation,neural magnetic field,magnetometry,nv centers,monte carlo,optogenetics,fiber optics,kubelka-munk model

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