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  1. Article ; Online: Markerless Mouse Tracking for Social Experiments.

    Le, Van Anh / Sterley, Toni-Lee / Cheng, Ning / Bains, Jaideep S / Murari, Kartikeya

    eNeuro

    2024  Volume 11, Issue 2

    Abstract: Automated behavior quantification in socially interacting animals requires accurate tracking. While many methods have been very successful and highly generalizable to different settings, issues of mistaken identities and lost information on key ... ...

    Abstract Automated behavior quantification in socially interacting animals requires accurate tracking. While many methods have been very successful and highly generalizable to different settings, issues of mistaken identities and lost information on key anatomical features are common, although they can be alleviated by increased human effort in training or post-processing. We propose a markerless video-based tool to simultaneously track two interacting mice of the same appearance in controlled settings for quantifying behaviors such as different types of sniffing, touching, and locomotion to improve tracking accuracy under these settings without increased human effort. It incorporates conventional handcrafted tracking and deep-learning-based techniques. The tool is trained on a small number of manually annotated images from a basic experimental setup and outputs body masks and coordinates of the snout and tail-base for each mouse. The method was tested on several commonly used experimental conditions including bedding in the cage and fiberoptic or headstage implants on the mice. Results obtained without any human corrections after the automated analysis showed a near elimination of identities switches and a ∼15% improvement in tracking accuracy over pure deep-learning-based pose estimation tracking approaches. Our approach can be optionally ensembled with such techniques for further improvement. Finally, we demonstrated an application of this approach in studies of social behavior of mice by quantifying and comparing interactions between pairs of mice in which some lack olfaction. Together, these results suggest that our approach could be valuable for studying group behaviors in rodents, such as social interactions.
    MeSH term(s) Animals ; Humans ; Algorithms ; Social Behavior ; Rodentia
    Language English
    Publishing date 2024-02-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0154-22.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: OSERR: an open-source standalone electrophysiology recording system for rodents.

    Cheng, Ning / Murari, Kartikeya

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 16996

    Abstract: Behavioral assessment of rodents is critical for investigation of brain function in health and disease. In vivo neurophysiological recordings are powerful tools to mechanistically dissect neural pathways that underlie behavioral changes, and serve as ... ...

    Abstract Behavioral assessment of rodents is critical for investigation of brain function in health and disease. In vivo neurophysiological recordings are powerful tools to mechanistically dissect neural pathways that underlie behavioral changes, and serve as markers for dynamics, efficacy and safety of potential therapeutic approaches. However, most in vivo recording systems require tethers or telemetry receivers, limiting their compatibility with some behavioral tests. Here, we developed an open-source standalone electrophysiology recording system for rodents (OSERR). It is a tether-free, standalone recording device with two channels, a reference and a ground, that acquires, amplifies, filters and stores data all in itself. Thus, it does not require any cable or receiver. It is also compact and light-weight, and compatible with juvenile mice, as well as multiple recording modalities and standard electrode implantation methods. In addition, we provide the complete design of hardware, and software for operation. As an example, we demonstrated that this standalone system, when configured with a bandwidth of 1-120 Hz and gain of 1000, successfully collected EEG signals during induced seizure, extended recording, anesthesia, and social interactions in mice. The design of this system is practical, economical, and freely available. Thus, this system could enable recording of brain activity during diverse behavioral assays in a variety of arenas and settings, and allow simultaneous recordings from multiple subjects to examine social behaviors. Importantly, with the open-source documentation, researchers could customize the design of the system to their specific needs.
    MeSH term(s) Animals ; Behavior, Animal ; Electrodes, Implanted ; Electrophysiological Phenomena ; Electrophysiology/instrumentation ; Electrophysiology/methods ; Male ; Mice ; Mice, Inbred C57BL ; Software ; Telemetry/instrumentation
    Language English
    Publishing date 2020-10-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-73797-4
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  3. Article ; Online: A clinically relevant selective ERK-pathway inhibitor reverses core deficits in a mouse model of autism.

    Murari, Kartikeya / Abushaibah, Abdulrahman / Rho, Jong M / Turner, Ray W / Cheng, Ning

    EBioMedicine

    2023  Volume 91, Page(s) 104565

    Abstract: Background: Extracellular signal-regulated kinase (ERK/MAPK) pathway in the brain is hypothesized to be a critical convergent node in the development of autism spectrum disorder. We reasoned that selectively targeting this pathway could reverse core ... ...

    Abstract Background: Extracellular signal-regulated kinase (ERK/MAPK) pathway in the brain is hypothesized to be a critical convergent node in the development of autism spectrum disorder. We reasoned that selectively targeting this pathway could reverse core autism-like phenotype in animal models.
    Methods: Here we tested a clinically relevant, selective inhibitor of ERK pathway, PD325901 (Mirdametinib), in a mouse model of idiopathic autism, the BTBR mice.
    Findings: We report that treating juvenile mice with PD325901 reduced ERK pathway activation, dose and duration-dependently reduced core disease-modeling deficits in sociability, vocalization and repetitive behavior, and reversed abnormal EEG signals. Further analysis revealed that subchronic treatment did not affect weight gain, locomotion, or neuronal density in the brain. Parallel treatment in the C57BL/6J mice did not alter their phenotype.
    Interpretation: Our data indicate that selectively inhibiting ERK pathway using PD325901 is beneficial in the BTBR model, thus further support the notion that ERK pathway is critically involved in the pathophysiology of autism. These results suggest that a similar approach could be applied to animal models of syndromic autism with dysregulated ERK signaling, to further test selectively targeting ERK pathway as a new approach for treating autism.
    Funding: This has beenwork was supported by Alberta Children's Hospital Research Foundation (JMR & NC), University of Calgary Faculty of Veterinary Medicine (NC), Kids Brain Health Network (NC), and Natural Sciences and Engineering Research Council of Canada (NC).
    MeSH term(s) Mice ; Animals ; Autistic Disorder/drug therapy ; Autistic Disorder/metabolism ; Autism Spectrum Disorder/metabolism ; Mice, Inbred C57BL ; MAP Kinase Signaling System ; Mice, Inbred Strains ; Disease Models, Animal
    Chemical Substances mirdametinib (86K0J5AK6M)
    Language English
    Publishing date 2023-04-21
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2023.104565
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  4. Article ; Online: Diffuse photon-remission associated with single-fiber geometry may be a simple scaling of that collected over the same area when under centered-illumination.

    Sun, Tengfei / Piao, Daqing / Yu, Linhui / Murari, Kartikeya

    Optics letters

    2021  Volume 46, Issue 19, Page(s) 4817–4820

    Abstract: Robust models for single-fiber reflectance (SFR) are relatively complex [Opt. Lett.45, 2078 (2020)OPLEDP0146-959210.1364/OL.385845] due to overlapping of the illumination and collection areas that entails probability weighting of the spatial integration ... ...

    Abstract Robust models for single-fiber reflectance (SFR) are relatively complex [Opt. Lett.45, 2078 (2020)OPLEDP0146-959210.1364/OL.385845] due to overlapping of the illumination and collection areas that entails probability weighting of the spatial integration of photon-remission. We demonstrate, via analytical means for limiting cases and Monte Carlo simulation of broader conditions, that diffuse photon-remission collected by single-fiber geometry may be scaled over the center-illuminated photon-remission. We specify for a medium revealing Henyey-Greenstein (HG) scattering anisotropy that the diffuse photon-remission from a sub-diffusive area of a top-hat illumination is ∼84.9
    Language English
    Publishing date 2021-09-30
    Publishing country United States
    Document type Journal Article
    ISSN 1539-4794
    ISSN (online) 1539-4794
    DOI 10.1364/OL.433233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Monitoring stimulus-evoked hemodynamic response during deep brain stimulation with single fiber spectroscopy.

    Yu, Linhui / Noor, M Sohail / Kiss, Zelma H T / Murari, Kartikeya

    Journal of biophotonics

    2022  Volume 15, Issue 11, Page(s) e202200076

    Abstract: Deep brain stimulation (DBS) is a revolutionary treatment for movement disorders. Measuring DBS-induced hemodynamic responses may be useful for surgical guidance of DBS electrode implantation as well as to study the mechanism and assess therapeutic ... ...

    Abstract Deep brain stimulation (DBS) is a revolutionary treatment for movement disorders. Measuring DBS-induced hemodynamic responses may be useful for surgical guidance of DBS electrode implantation as well as to study the mechanism and assess therapeutic effects of DBS. In this study, we evaluated the performance of a single fiber spectroscopic (SFS) system for measuring hemodynamic response in different cortical layers in a DBS animal model. We showed that SFS is capable of measuring minute relative changes in oxygen saturation and blood volume fraction in-vivo at a sampling rate of 22-33 Hz. During stimulation, blood volume fraction increased, while oxygen saturation showed both increases and decreases at different cortical depths across animals. In addition, we showed the potential of using SFS for measuring other physiological parameters, for example, heart rate, and respiratory rate.
    MeSH term(s) Animals ; Deep Brain Stimulation/methods ; Spectrum Analysis ; Hemodynamics
    Language English
    Publishing date 2022-08-21
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2390063-5
    ISSN 1864-0648 ; 1864-063X
    ISSN (online) 1864-0648
    ISSN 1864-063X
    DOI 10.1002/jbio.202200076
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  6. Article ; Online: Induced pluripotency in the context of stem cell expansion bioprocess development, optimization, and manufacturing: a roadmap to the clinic.

    Colter, James / Murari, Kartikeya / Biernaskie, Jeff / Kallos, Michael Scott

    NPJ Regenerative medicine

    2021  Volume 6, Issue 1, Page(s) 72

    Abstract: The translation of laboratory-scale bioprocess protocols and technologies to industrial scales and the application of human induced pluripotent stem cell (hiPSC) derivatives in clinical trials globally presents optimism for the future of stem-cell ... ...

    Abstract The translation of laboratory-scale bioprocess protocols and technologies to industrial scales and the application of human induced pluripotent stem cell (hiPSC) derivatives in clinical trials globally presents optimism for the future of stem-cell products to impact healthcare. However, while many promising therapeutic approaches are being tested in pre-clinical studies, hiPSC-derived products currently account for a small fraction of active clinical trials. The complexity and volatility of hiPSCs present several bioprocessing challenges, where the goal is to generate a sufficiently large, high-quality, homogeneous population for downstream differentiation-the derivatives of which must retain functional efficacy and meet regulatory safety criteria in application. It is argued herein that one of the major challenges currently faced in improving the robustness of routine stem-cell biomanufacturing is in utilizing continuous, meaningful assessments of molecular and cellular characteristics from process to application. This includes integrating process data with biological characteristic and functional assessment data to model the interplay between variables in the search for global optimization strategies. Coupling complete datasets with relevant computational methods will contribute significantly to model development and automation in achieving process robustness. This overarching approach is thus crucially important in realizing the potential of hiPSC biomanufacturing for transformation of regenerative medicine and the healthcare industry.
    Language English
    Publishing date 2021-11-01
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2057-3995
    ISSN (online) 2057-3995
    DOI 10.1038/s41536-021-00183-7
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  7. Article ; Online: Redox-Concatenated Aptamer Integrated Skin Mimicking Electrochemical Patch for Noninvasive Detection of Cortisol.

    Janghorban, Mohammad / Aradanas, Irvyne / Malaeb, Karem / Abuelazm, Habiba / Nittala, Aditya / Hu, Jinguang / Murari, Kartikeya / Pandey, Richa

    ACS sensors

    2023  Volume 9, Issue 2, Page(s) 799–809

    Abstract: This research focuses on developing and validating a wearable electrochemical biosensor called the concatenated aptamer integrated skin patch, also known as the Captain Patch. The main objective is to detect cortisol levels in sweat, which can provide ... ...

    Abstract This research focuses on developing and validating a wearable electrochemical biosensor called the concatenated aptamer integrated skin patch, also known as the Captain Patch. The main objective is to detect cortisol levels in sweat, which can provide valuable insights into an individual's health. The biosensor utilizes a corrugated surface that mimics the skin, allowing for better attachment and an improved electrochemical performance. The study demonstrates the successful application of Captain Patch on the human body by using artificially spiked sweat samples. The results indicate good measurement accuracy and conformity when the patch is worn on the body. However, for long-term usage, the patch needs to be changed every 3-4 h or worn three times a day to enable monitoring of cortisol levels. Despite the need for frequent patch changes, the cost-effectiveness and ease of operation make these skin patches suitable for longitudinal cortisol monitoring and other sweat analytes. By customization of the biorecognition probe, the developed biowearable can be used to monitor a variety of vital biomarkers. Overall, Captain Patch, with its capability of detecting specific health markers such as cortisol, hints at the future potential of wearables to offer valuable data on various other biomarkers. Our approach presents the first step in integrating a cost-effective wearable electrochemical patch integrated with a redox-concatenated aptamer for noninvasive biomarker detection. This personalized approach to monitoring can lead to improved patient outcomes and increased patient engagement in managing their health.
    MeSH term(s) Humans ; Wearable Electronic Devices ; Hydrocortisone ; Biosensing Techniques/methods ; Oxidation-Reduction ; Biomarkers
    Chemical Substances Hydrocortisone (WI4X0X7BPJ) ; Biomarkers
    Language English
    Publishing date 2023-12-26
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3694
    ISSN (online) 2379-3694
    DOI 10.1021/acssensors.3c02110
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  8. Article ; Online: Neurovascular coupling during deep brain stimulation.

    Noor, M Sohail / Yu, Linhui / Murari, Kartikeya / Kiss, Zelma Ht

    Brain stimulation

    2020  Volume 13, Issue 3, Page(s) 916–927

    Abstract: Background: Deep brain stimulation (DBS) is an effective treatment for movement disorders, yet its mechanisms of action remain unclear. One method used to study its circuit-wide neuromodulatory effects is functional magnetic resonance imaging (fMRI) ... ...

    Abstract Background: Deep brain stimulation (DBS) is an effective treatment for movement disorders, yet its mechanisms of action remain unclear. One method used to study its circuit-wide neuromodulatory effects is functional magnetic resonance imaging (fMRI) which measures hemodynamics as a proxy of neural activity. To interpret functional imaging data, we must understand the relationship between neural and vascular responses, which has never been studied with the high frequencies used for DBS.
    Objective: To measure neurovascular coupling in the rat motor cortex during thalamic DBS.
    Method: Simultaneous intrinsic optical imaging and extracellular electrophysiology was performed in the motor cortex of urethane-anesthetized rats during thalamic DBS at 7 different frequencies. We related Maximum Change in Reflectance (MCR) from the imaging data to Integrated Evoked Potential (IEP) and change in broadband power of multi-unit (MU) activity, computing Spearman's correlation to determine the strength of these relationships. To determine the source of these effects, we studied the contributions of antidromic versus orthodromic activation in motor cortex perfusion using synaptic blockers.
    Results: MCR, IEP and change in MU power increased linearly to 60 Hz and saturated at higher frequencies of stimulation. Blocking orthodromic transmission only reduced the DBS-induced change in optical signal by ∼25%, suggesting that activation of corticofugal fibers have a major contribution in thalamic-induced cortical activation.
    Conclusion: DBS-evoked vascular response is related to both evoked field potentials as well as multi-unit activity.
    MeSH term(s) Animals ; Deep Brain Stimulation/methods ; Evoked Potentials/physiology ; Magnetic Resonance Imaging/methods ; Male ; Motor Cortex/diagnostic imaging ; Motor Cortex/physiology ; Neurovascular Coupling/physiology ; Rats ; Rats, Sprague-Dawley ; Thalamus/diagnostic imaging ; Thalamus/physiology
    Language English
    Publishing date 2020-03-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2394410-9
    ISSN 1876-4754 ; 1935-861X
    ISSN (online) 1876-4754
    ISSN 1935-861X
    DOI 10.1016/j.brs.2020.03.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Design of a single-fiber, wavelength-resolved system for monitoring deep tissue oxygenation.

    Yu, Linhui / Murari, Kartikeya

    Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

    2015  Volume 2014, Page(s) 3707–3710

    Abstract: We propose a single-fiber, zero source-detector separation system with wavelength-resolved detection for measuring oxygen saturation in deep brain structures. The system consists of a white light emitting diode (LED) source, optics to couple light into a ...

    Abstract We propose a single-fiber, zero source-detector separation system with wavelength-resolved detection for measuring oxygen saturation in deep brain structures. The system consists of a white light emitting diode (LED) source, optics to couple light into a 240-μm-diameter fiber, a beam splitter to separate the collected from the delivered photons and a spectrometer for detection. Depth resolution is achieved by inserting the fiber, comparable in size to microelectrodes used for electrophysiology, into the tissue of interest. Since most of the diffuse reflected light travels through a small volume at the tip of the fiber, this arrangement allows efficient collection of signal. Fresnel reflections are minimized using polarizers. Monte Carlo simulations across 400-1000 nm indicate that ~0.5% of the incident light can be collected and effectively interrogate a ~0.02 mm(3) volume at the fiber tip. System design, characterization data and phantom experiments using an absorptive dye in scattering media are presented. The simple nature of the instrumentation can potentially lead to a miniaturized system capable of detecting oxygen saturation in deep brain structures in freely-moving animals.
    MeSH term(s) Animals ; Brain/metabolism ; Hemoglobins/chemistry ; Hemoglobins/metabolism ; Light ; Miniaturization ; Monte Carlo Method ; Oxygen/analysis ; Phantoms, Imaging ; Photons ; Spectroscopy, Near-Infrared/instrumentation ; Spectroscopy, Near-Infrared/methods
    Chemical Substances Hemoglobins ; Oxygen (S88TT14065)
    Language English
    Publishing date 2015-01-06
    Publishing country United States
    Document type Journal Article
    ISSN 2694-0604
    ISSN (online) 2694-0604
    DOI 10.1109/EMBC.2014.6944428
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  10. Article: Fiber photometry for monitoring cerebral oxygen saturation in freely-moving rodents.

    Yu, Linhui / Thurston, Elizabeth M S / Hashem, Mada / Dunn, Jeff F / Whelan, Patrick J / Murari, Kartikeya

    Biomedical optics express

    2020  Volume 11, Issue 7, Page(s) 3491–3506

    Abstract: Hemodynamic parameters, such as tissue oxygen saturation and blood volume fraction, are important markers of brain physiology. They are also widely used surrogate markers of electrophysiological activity. Here, we present a single fiber spectroscopic ( ... ...

    Abstract Hemodynamic parameters, such as tissue oxygen saturation and blood volume fraction, are important markers of brain physiology. They are also widely used surrogate markers of electrophysiological activity. Here, we present a single fiber spectroscopic (SFS) system for monitoring cerebral oxygen saturation in localized, non-line-of-sight brain regions in freely-moving rodents. We adapted the implantation ferrule and patch cable design from commercialized optogenetics and fiber photometry systems, enabling stereotaxic fiber implantation, longitudinal tissue access and measurement from freely-moving animals. The optical system delivers and collects light from the brain through a 200
    Language English
    Publishing date 2020-06-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2572216-5
    ISSN 2156-7085
    ISSN 2156-7085
    DOI 10.1364/BOE.393295
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