Biomedical Engineering - Research Publications

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    Computational Fluid Dynamics of Stent-Mounted Neural Interfaces in an Idealized Cerebral Venous Sinus.
    Qi, W ; Ooi, A ; Grayden, DB ; John, SE (IEEE, 2023-07)
    Hemodynamic changes in stented blood vessels play a critical role in stent-associated complications. The majority of work on the hemodynamics of stented blood vessels has focused on coronary arteries but not cerebral venous sinuses. With the emergence of endovascular electrophysiology, there is a growing interest in stenting cerebral blood vessels. We investigated the hemodynamic impact of a stent-mounted neural interface inside the cerebral venous sinus. The stent was virtually implanted into an idealized superior sagittal sinus (SSS) model. Local venous blood flow was simulated. Results showed that blood flow was altered by the stent, generating recirculation and low wall shear stress (WSS) around the device. However, the effect of the electrodes on blood flow was not prominent due to their small size. This is an early exploration of the hemodynamics of a stent-mounted neural interface. Future work will shed light on the key factors that influence blood flow and stenting outcomes.Clinical Relevance-The study investigates blood flow through a stent-based electrode array inside the cerebral venous sinus. The hemodynamic impact of the stent can provide insight into neointimal growth and thrombus formation.
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    Predictive Shared Control of Robotic Arms Using Simulated Brain-Computer Interface Inputs
    Kokorin, K ; Mu, J ; John, SE ; Grayden, DB (IEEE, 2023)
    Low decoding accuracy makes brain-computer interface (BCI) control of a robotic arm difficult. Shared control (SC) can overcome limitations of a BCI by leveraging external sensor data and generating commands to assist the user. Our study explored whether reaching targets with a robot end-effector was easier using SC rather than direct control (DC). We simulated a motor imagery BCI using a joystick with noise introduced to explicitly control interface accuracy to be 65% or 79%. Compared to DC, our prediction-based implementation of SC led to a significant reduction in the trajectory length of successful reaches for 4 (3) out of 5 targets using the 65% (79%) accurate interface, with failure rates being equivalent to DC for 2 (1) out of 5 targets. Therefore, this implementation of SC is likely to improve reaching efficiency but at the cost of more failures. Additionally, the NASA Task Load Index results suggest SC reduced user workload.Clinical relevance-Shared control can minimise the impact of BCI decoder errors on robot motion, making robotic arm control using noninvasive BCIs more viable.
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    Wearable Transmitter Coil Design for Inductive Wireless Power Transfer to Implantable Devices.
    Tai, Y-D ; Widdicombe, B ; Unnithan, RR ; Grayden, DB ; John, SE (IEEE, 2023-07)
    Wireless endovascular sensors and stimulators are emerging biomedical technologies for applications such as endovascular pressure monitoring, hyperthermia, and neural stimulations. Recently, coil-shaped stents have been proposed for inductive power transfer to endovascular devices using the stent as a receiver. However, less work has been done on the external transmitter components, so the maximum power transferable remains unknown. In this work, we design and evaluate a wearable transmitter coil that allows 50 mW power transfer in simulation.Clinical Relevance-This allows more accurate measurements and precise control of endovascular devices.
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    Electrochemistry in a Two- or Three-Electrode Configuration to Understand Monopolar or Bipolar Configurations of Platinum Bionic Implants
    Harris, AR ; Grayden, DB ; John, SE (MDPI, 2023-04)
    Electrodes are used in vivo for chemical sensing, electrophysiological recording, and stimulation of tissue. The electrode configuration used in vivo is often optimised for a specific anatomy and biological or clinical outcomes, not electrochemical performance. Electrode materials and geometries are constrained by biostability and biocompatibility issues and may be required to function clinically for decades. We performed benchtop electrochemistry, with changes in reference electrode, smaller counter-electrode sizes, and three- or two-electrode configurations. We detail the effects different electrode configurations have on typical electroanalytical techniques used on implanted electrodes. Changes in reference electrode required correction by application of an offset potential. In a two-electrode configuration with similar working and reference/counter-electrode sizes, the electrochemical response was dictated by the rate-limiting charge transfer step at either electrode. This could invalidate calibration curves, standard analytical methods, and equations, and prevent use of commercial simulation software. We provide methods for determining if an electrode configuration is affecting the in vivo electrochemical response. We recommend sufficient details be provided in experimental sections on electronics, electrode configuration, and their calibration to justify results and discussion. In conclusion, the experimental limitations of performing in vivo electrochemistry may dictate what types of measurements and analyses are possible, such as obtaining relative rather than absolute measurements.
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    Vascular remodeling in sheep implanted with endovascular neural interface
    John, SE ; Donegan, S ; Scordas, TC ; Qi, W ; Sharma, P ; Liyanage, K ; Wilson, S ; Birchall, I ; Ooi, A ; Oxley, TJ ; May, CN ; Grayden, DB ; Opie, NL (IOP Publishing Ltd, 2022-10-01)
    Objective.The aim of this work was to assess vascular remodeling after the placement of an endovascular neural interface (ENI) in the superior sagittal sinus (SSS) of sheep. We also assessed the efficacy of neural recording using an ENI.Approach.The study used histological analysis to assess the composition of the foreign body response. Micro-CT images were analyzed to assess the profiles of the foreign body response and create a model of a blood vessel. Computational fluid dynamic modeling was performed on a reconstructed blood vessel to evaluate the blood flow within the vessel. Recording of brain activity in sheep was used to evaluate efficacy of neural recordings.Main results.Histological analysis showed accumulated extracellular matrix material in and around the implanted ENI. The extracellular matrix contained numerous macrophages, foreign body giant cells, and new vascular channels lined by endothelium. Image analysis of CT slices demonstrated an uneven narrowing of the SSS lumen proportional to the stent material within the blood vessel. However, the foreign body response did not occlude blood flow. The ENI was able to record epileptiform spiking activity with distinct spike morphologies.Significance. This is the first study to show high-resolution tissue profiles, the histological response to an implanted ENI and blood flow dynamic modeling based on blood vessels implanted with an ENI. The results from this study can be used to guide surgical planning and future ENI designs; stent oversizing parameters to blood vessel diameter should be considered to minimize detrimental vascular remodeling.
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    Computational modeling of endovascular peripheral nerve stimulation using a stent-mounted electrode array
    Liu, JY ; Grayden, DB ; Keast, JR ; John, SE (IOP Publishing Ltd, 2023-06-01)
    Objective.Endovascular neuromodulation has attracted substantial interest in recent years as a minimally invasive approach to treat neurological disorders. In this study, we investigated with a computational model the feasibility of stimulating peripheral nerves with an endovascular stent-mounted electrode array.Approach.Anatomically realistic FEM models were constructed for the pudendal and vagal neurovascular bundles. The electromagnetic fields generated from electrical stimuli were computed using Sim4Life NEURON models to predict dynamic axonal responses.Main results.The models predict that the stimulation thresholds of the endovascular stent-electrode array configurations tested are comparable to that of ring electrodes and are dependent on the inter-electrode distance and orientation of the device. Arranging multiple electrodes along the longitudinal axis of the nerve lowers surface charge density without sacrificing axon recruitment, whereas arranging electrodes along the circumference of the blood vessel reduces the risk of misalignment but lowers axon recruitment.Significance.Overall, this study predicts that the endovascular stent-electrode array is a feasible stimulation option for peripheral nerves, and the electrode array can be flexibly optimized to achieve the lowest stimulation threshold.
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    Longwave infrared multispectral image sensor system using aluminum-germanium plasmonic filter arrays
    Shaik, NEK ; Widdicombe, B ; Sun, D ; John, SEE ; Ryu, D ; Nirmalathas, A ; Unnithan, RRR (TSINGHUA UNIV PRESS, 2023-07)
    Abstract A multispectral camera records image data in various wavelengths across the electromagnetic spectrum to acquire additional information that a conventional camera fails to capture. With the advent of high-resolution image sensors and color filter technologies, multispectral imagers in the visible wavelengths have become popular with increasing commercial viability in the last decade. However, multispectral imaging in longwave infrared (LWIR, 8–14 μm) is still an emerging area due to the limited availability of optical materials, filter technologies, and high-resolution sensors. Images from LWIR multispectral cameras can capture emission spectra of objects to extract additional information that a human eye fails to capture and thus have important applications in precision agriculture, forestry, medicine, and object identification. In this work, we experimentally demonstrate an LWIR multispectral image sensor with three wavelength bands using optical elements made of an aluminum (Al)-based plasmonic filter array sandwiched in germanium (Ge). To realize the multispectral sensor, the filter arrays are then integrated into a three-dimensional (3D) printed wheel stacked on a low-resolution monochrome thermal sensor. Our prototype device is calibrated using a blackbody and its thermal output has been enhanced with computer vision methods. By applying a state-of-the-art deep learning method, we have also reconstructed multispectral images to a better spatial resolution. Scientifically, our work demonstrates a versatile spectral thermography technique for detecting target signatures in the LWIR range and other advanced spectral analyses.
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    Preliminary Minimum Reporting Requirements for In-Vivo Neural Interface Research: I. Implantable Neural Interfaces
    Eiber, C ; Delbeke, J ; Cardoso, J ; de Neeling, M ; John, S ; Lee, CW ; Skefos, J ; Sun, A ; Prodanov, D ; McKinney, Z (Institute of Electrical and Electronics Engineers (IEEE), 2021)
    The pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such standards for neurotechnologies limits the transparency, reproducibility, and meta-analysis of this growing body of research, posing an ongoing barrier to research, clinical, and commercial objectives. Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by a full spectrum of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE Working Group P2794, developing a Reporting Standard for in-vivo Neural Interface Research (RSNIR). Index Terms— Neurotechnology, reproducibility, scientific reporting, standardization, bioelectronic medicine Impact Statement— This work provides a preliminary set of reporting guidelines for implantable neural interface research, developed by IEEE WG P2794 in open collaboration between a range of stakeholders to accelerate the research, development, and integration of innovative neurotechnologies.
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    Motor neuroprosthesis implanted with neurointerventional surgery improves capacity for activities of daily living tasks in severe paralysis: first in-human experience
    Oxley, TJ ; Yoo, PE ; Rind, GS ; Ronayne, SM ; Lee, CMS ; Bird, C ; Hampshire, V ; Sharma, RP ; Morokoff, A ; Williams, DL ; MacIsaac, C ; Howard, ME ; Irving, L ; Vrljic, I ; Williams, C ; John, SE ; Weissenborn, F ; Dazenko, M ; Balabanski, AH ; Friedenberg, D ; Burkitt, AN ; Wong, YT ; Drummond, KJ ; Desmond, P ; Weber, D ; Denison, T ; Hochberg, LR ; Mathers, S ; O'Brien, TJ ; May, CN ; Mocco, J ; Grayden, DB ; Campbell, BC ; Mitchell, P ; Opie, NL (BMJ PUBLISHING GROUP, 2021-02)
    BACKGROUND: Implantable brain-computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation. METHODS: Two participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks. RESULTS: Unsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%-100.00%) (trial mean (median, Q1-Q3)) at a rate of 13.81 (13.44, 10.96-16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%-100.00%) at 20.10 (17.73, 12.27-26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants. CONCLUSION: We describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis.
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    Distinct Neural Correlates Underlie Inhibitory Mechanisms of Motor Inhibition and Motor Imagery Restraint
    Yoo, PE ; Oxley, TJ ; Hagan, MA ; John, S ; Ronayne, SM ; Rind, GS ; Brinded, AM ; Opie, NL ; Moffat, BA ; Wong, YT (Frontiers Media, 2020-06-03)
    There is evidence to suggest that motor execution and motor imagery both involve planning and execution of the same motor plan, however, in the latter the output is inhibited. Currently, little is known about the underlying neural mechanisms of motor output inhibition during motor imagery. Uncovering the distinctive characteristics of motor imagery may help us better understand how we abstract complex thoughts and acquire new motor skills. The current study aimed to dissociate the cognitive processes involved in two distinct inhibitory mechanisms of motor inhibition and motor imagery restraint. Eleven healthy participants engaged in an imagined GO/NO-GO task during a 7 Tesla fMRI experiment. Participants planned a specific type of motor imagery, then, imagined the movements during the GO condition and restrained from making a response during the NO-GO condition. The results revealed that specific sub-regions of the supplementary motor cortex (SMC) and the primary motor cortex (M1) were recruited during the imagination of specific movements and information flowed from the SMC to the M1. Such condition-specific recruitment was not observed when motor imagery was restrained. Instead, general recruitment of the posterior parietal cortex (PPC) was observed, while the BOLD activity in the SMC and the M1 decreased below the baseline at the same time. Information flowed from the PPC to the SMC, and recurrently between the M1 and the SMC, and the M1 and the PPC. These results suggest that motor imagery involves task-specific motor output inhibition partly imposed by the SMC to the M1, while the PPC globally inhibits motor plans before they are passed on for execution during the restraint of responses.