Methods of magnetic field switching for biomedical and power applications

Surrounded by electromagnetic (EM) fields humans continuously interact and utilize EM fields for domestic devices, telecom systems, power systems and different medical applications including MRI (Magnetic Resonance Imaging) and TMS (Transcranial Magnetic Stimulation). During the last century, numerous new electronic devices and technologies have been developed leading to an exponential increase in exposure to Electromagnetic Fields. Although all of these applications are byproducts of Maxwell\u27 experimentation, there are considerable differences in the way they interact with us. In the treatment of noninvasive treatment of the human brain, the majority of the research has been mainly focused on realizing systems that can produce gigantic current and magnetic fields. Transcranial Magnetic Stimulation (TMS) in this application has provided numerous opportunities and possibilities. It has shown more promise in the therapeutic role for treatment of neurological disorders. TMS researchers are working towards improving the technical developmental tools for modeling, and magnetic field generation study for deep body penetration. The development stage of these devices with associated risks in manufacturing, tight medical tolerances, cost and reliability pose important research challenges which are addressed in this research. The objective of this research is to understand, develop and offer alternative methods for the implementation of several magnetic field generators that satisfy the requirement for magnetic field applications in medical, and other fields. This work presents a continual progression of the magnetic field generators from larger scale to small scale with variable energy consumption, high speed, and deployable systems. Additionally challenges and practical designs are presented

Neurostimulator with Waveforms Inspired by Nature for Wearable Electro-Acupuncture

The work presented here has 3 goals: establish the need for novel neurostimulation waveform solutions through a literature review, develop a neurostimulation pulse generator, and verify the operation of the device for neurostimulation applications. The literature review discusses the importance of stimulation waveforms on the outcomes of neurostimulation, and proposes new directions for neurostimulation research that would help in improving the reproducibility and comparability between studies. The pulse generator circuit is then described that generates signals inspired by the shape of excitatory or inhibitory post-synaptic potentials (EPSP, IPSP). The circuit analytical equations are presented, and the effects of the circuit design components are discussed. The circuit is also analyzed with a capacitive load using a simplified Randles model to represent the electrode-electrolyte interface, and the output is measured in phosphate-buffered saline (PBS) solution as the load with acupuncture needles as electrodes. The circuit is designed to be used in different types of neurostimulators depending on the needs of the application, and to study the effects of varying neurostimulation waveforms. The circuit is used to develop a remote-controlled wearable veterinary electro-acupuncture machine. The device has a small form-factor and 3D printed enclosure, and has a weight of 75 g with leads attached. The device is powered by a 500 mAh lithium polymer battery, and was tested to last 6 hours. The device is tested in an electro-acupuncture animal study on cats performed at the Louisiana State University School of Veterinary Medicine, where it showed expected electro-acupuncture effects. Then, a 2-channel implementation of the device is presented, and tested to show independent output amplitude, frequency, and stimulation duration per channel. Finally, the software and hardware requirements for control of the wearable veterinary electro-acupuncture machine are detailed. The number of output channels is limited to the number of hardware PWM timers available for use. The Arduino software implements PWM control for the output amplitude and frequency. The stimulation duration control is provided using software timers. The communications protocol between the microcontroller board and Android App are described, and communications are performed via Bluetooth

Non-Invasive Picosecond Pulse System for Electrostimulation

Picosecond pulsed electric fields have been shown to have stimulatory effects, such as calcium influx, activation of action potential, and membrane depolarization, on biological cells. Because the pulse duration is so short, it has been hypothesized that the pulses permeate a cell and can directly affect intracellular cell structures by bypassing the shielding of the membrane. This provides an opportunity for studying new biophysics. Furthermore, radiating picosecond pulses can be efficiently done by a compact antenna because the antenna size is comparable to the pulse width. However, all of the previous bioelectric studies regarding picosecond pulses have been conducted in vitro, using electrodes. There is not yet a device which can non-invasively deliver picosecond-pulsed electric fields to neurological tissue for therapeutic applications. It is unclear whether a radiated electric field at a given penetration depth can reach the threshold to cause biological effects. In this dissertation, a picosecond- pulsed electric field system designed for the electrosimulation of neural cells is presented. This begins with the design of an ultra-wideband biconical dielectric rod antenna. It consists of a dielectrically loaded V-conical launcher which feeds a cylindrical waveguide. The waveguide then transitions into a taper, which acts like a lens to focus the energy in the tissue target. To describe the antenna delivery of picosecond pulses to tissues, the initial performance was simulated using a 3-layer tissue model and then a human head model. The final model was shown to effectively deliver pulses of 11.5 V/m to the brain for a 1 V input. The spot size of the stimulation is on the order of 1 cm. The electric field was able to penetrate to a depth of 2 cm, which is equal to the pulse width of a 200 ps pulse. The antenna was constructed and characterized in free space in time domain and in frequency domain. The experimental results have a good agreement with the simulation. The ultimate biological application relies on adequate electric field. To reach a threshold electric field for effective stimulation, the antenna should be driven by a high voltage, picosecond-pulsed power supply, which, in our case, consists of a nanosecond charging transformer, a parallel-plate transmission line, and a picosecond discharging switch. This transformer was used to charge a parallel-plate transmission line, with the antenna as the load. To generate pulses with a rise time of hundreds of picoseconds, an oil switch with a millimeter gap was used. For the charging, a dual resonance pulse transformer was designed and constructed. The novel aspect of this transformer is has a fast charge time. It was shown to be capable of producing over 100 kV voltages in less than 100 ns. After the closing of the peaking switch and the picosecond rise time generation, the antenna was able to create an electric field of 600 V/cm in the air at a distance of 3 cm. This field was comparable to the simulation. Higher voltage operation was met with dielectric breakdown across the insulation layer that separates the high voltage side and the ground side. Before the designed antenna is used in vivo, it is critical to determine the biological effect of picosecond pulses. This is especially important if we focus on stimulatory effects, which require that the electric field intensity be close to the range that the antenna system can deliver. Toward that end, neural stem cells were chosen to study for the proliferation, metabolism, and gene expression. Instead of using the antenna, the electrodes were used to deliver the pulses to the cells. In order to treat enough cells for downstream analyses, the electrodes were mounted on a 3-D printer head, which could be moved freely and could be controlled accurately by programming. The results show that pulses on the order of 20 kV/cm affect the proliferation, metabolism, and gene expression of both neural and mesenchymal stem cells, without reducing viability. In general, we came to the conclusion that picosecond pulses can be a useful stimulus for a variety of applications, but the possibility of using antennas to directly stimulate tissue functions relies on the development of a pulsed power system, high voltage insulation, and antenna material

Numerical modelling in transcranial magnetic stimulation

Tese de doutoramento, Engenharia Biomédica e Biofísica, Universidade de Lisboa, Faculdade de Ciências, 2009In this work powerful numerical methods were used to study several problems that still remain unsolved in TMS.The first problem that was studied is related to the difficulties that arise when stimulating sub-cortical deep regions with TMS, due to the fact that the induced field rapidly decays and loses focality with depth. This study's approach to overcome this difficulty was to combine ferromagnetic cores with a coil designed to induce an electric field that decays slowly. The efficacy of this approach was tested by using the FEM to calculate the field induced by this coil / core design in a realistically shaped head model. The results show that the core might make this coil even more suited for deep brain stimulation.The second problem that was tackled is related to the lack of knowledge about the dominant mechanisms through which the induced electric field excites neurons in TMS. In this work the electric field along lines, representing trajectories of actual cortical neurons, was calculated using the FEM. The neurons were embedded in a realistically shaped sulcus model, with a figure-8 coil placed above the model. The electric field was then incorporated into the cable equation. The solution of the latter allowed the determination of the site and threshold of activation of the neurons. The results highlight the importance of axonal terminations and bends and tissue heterogeneities on stimulation of neurons.The third problem that was studied concerns TMS of small animals and the lack of knowledge about the optimal geometry, size and orientation of the used coils. This was studied by using the FEM to calculate the electric field induced in a realistically shaped mouse model by several commercially available coils. The results showed that the smaller coils induced fields with higher magnitude, better focality, and smaller decay than the bigger coils.These results highlight the importance of numerical modelling in TMS, either in coil design, determination of basic neurophysiologic mechanisms or optimization of experimental procedures

High power magnetic stimulation of the peripheral nervous system and the upper urinary tract.

In theory many of the physiological effects of electrical stimulation should be repeatable with magnetic stimulation. The aim of this study was to investigate some of the potentially clinically relevant actions of high power magnetic stimulation on the mammalian peripheral nervous system. This investigation can be separated into 3 parts. Firstly, experiments examining the ability of 'wide pulse' electrical stimulation to produce complete reversible block of peripheral nerve were undertaken at both the compound and single unit level. The findings were used to estimate the magnitude of an impulse magnetic field required to produce 'magnetic nerve block'. Secondly, the design and construction of two prototype high power magnetic stimulators (HPMS) and their associated filed coils was carried out. Theoretical predictions and practical measurements of the output of each stimulator were undertaken. Thirdly physiological experiments with the HPMS's were performed, examining magnetic stimulation of unmyelinated nerve fibres in the upper renal tract. The aim of stimulating the kidney was to generate ureteric peristalsis, which may have a role in aiding stone excretion, especially post lithotripsy. For the electrical nerve block study the saphenous nerve in anaesthetized rats and rabbits was exposed. Either the whole nerve or fine filaments dissected from the cut proximal end of the nerve were studied. A-ap, A- 5 and C fibres were stimulated and blocked by wide electrical pulses with an exponential decay. The strength duration relationship of this response was studied and block was confirmed by failure of conduction of a proximally generated action potential to pass through the blocked region. Two HPMS's were designed and constructed in conjunction with Digitimer Ltd. and the department of Electrical and Electronic Engineering at Loughborough University. The first prototype was rated at 4.3 KJ and the second at 96KJ. Early on in structural testing it was found that conventional coil design was insufficient to allow repetitive shots, particularly with the 96KJ device. Redesign of the coil housing allowed multiple stimuli without failure. Finally physiological experiments with the prototype HPMS's demonstrated stimulation of C-fibres in the upper renal tract in a pig model. Magnetic stimulation of the kidney was able to generate ureteric peristalsis in the in-situ and exteriorized kidney preparations studied. Local anaesthetic applied topically to the renal pelvis and calyces blocked this response indicating that magnetic stimulation of ureteric peristalsis is a neurally mediated phenomenon. This thesis demonstrates that high power magnetic stimulation is technically feasible from both an engineering and physiological perspective. It can activate all classes of nerve fibre allowing the extracorporeal stimulation of internal organs

Real-Time Artifacts Reduction during TMS-EEG Co-Registration: A Comprehensive Review on Technologies and Procedures

Transcranial magnetic stimulation (TMS) excites neurons in the cortex, and neural activity can be simultaneously recorded using electroencephalography (EEG). However, TMS-evoked EEG potentials (TEPs) do not only reflect transcranial neural stimulation as they can be contaminated by artifacts. Over the last two decades, significant developments in EEG amplifiers, TMS-compatible technology, customized hardware and open source software have enabled researchers to develop approaches which can substantially reduce TMS-induced artifacts. In TMS-EEG experiments, various physiological and external occurrences have been identified and attempts have been made to minimize or remove them using online techniques. Despite these advances, technological issues and methodological constraints prevent straightforward recordings of early TEPs components. To the best of our knowledge, there is no review on both TMS-EEG artifacts and EEG technologies in the literature to-date. Our survey aims to provide an overview of research studies in this field over the last 40 years. We review TMS-EEG artifacts, their sources and their waveforms and present the state-of-the-art in EEG technologies and front-end characteristics. We also propose a synchronization toolbox for TMS-EEG laboratories. We then review subject preparation frameworks and online artifacts reduction maneuvers for improving data acquisition and conclude by outlining open challenges and future research directions in the field

소형동물의 뇌신경 자극을 위한 완전 이식형 신경자극기

학위논문(박사)--서울대학교 대학원 :공과대학 전기·정보공학부,2020. 2. 김성준.In this study, a fully implantable neural stimulator that is designed to stimulate the brain in the small animal is described. Electrical stimulation of the small animal is applicable to pre-clinical study, and behavior study for neuroscience research, etc. Especially, behavior study of the freely moving animal is useful to observe the modulation of sensory and motor functions by the stimulation. It involves conditioning animal's movement response through directional neural stimulation on the region of interest. The main technique that enables such applications is the development of an implantable neural stimulator. Implantable neural stimulator is used to modulate the behavior of the animal, while it ensures the free movement of the animals. Therefore, stable operation in vivo and device size are important issues in the design of implantable neural stimulators. Conventional neural stimulators for brain stimulation of small animal are comprised of electrodes implanted in the brain and a pulse generation circuit mounted on the back of the animal. The electrical stimulation generated from the circuit is conveyed to the target region by the electrodes wire-connected with the circuit. The devices are powered by a large battery, and controlled by a microcontroller unit. While it represents a simple approach, it is subject to various potential risks including short operation time, infection at the wound, mechanical failure of the device, and animals being hindered to move naturally, etc. A neural stimulator that is miniaturized, fully implantable, low-powered, and capable of wireless communication is required. In this dissertation, a fully implantable stimulator with remote controllability, compact size, and minimal power consumption is suggested for freely moving animal application. The stimulator consists of modular units of surface-type and depth-type arrays for accessing target brain area, package for accommodating the stimulating electronics all of which are assembled after independent fabrication and implantation using customized flat cables and connectors. The electronics in the package contains ZigBee telemetry for low-power wireless communication, inductive link for recharging lithium battery, and an ASIC that generates biphasic pulse for neural stimulation. A dual-mode power-saving scheme with a duty cycling was applied to minimize the power consumption. All modules were packaged using liquid crystal polymer (LCP) to avoid any chemical reaction after implantation. To evaluate the fabricated stimulator, wireless operation test was conducted. Signal-to-Noise Ratio (SNR) of the ZigBee telemetry were measured, and its communication range and data streaming capacity were tested. The amount of power delivered during the charging session depending on the coil distance was measured. After the evaluation of the device functionality, the stimulator was implanted into rats to train the animals to turn to the left (or right) following a directional cue applied to the barrel cortex. Functionality of the device was also demonstrated in a three-dimensional maze structure, by guiding the rats to navigate better in the maze. Finally, several aspects of the fabricated device were discussed further.본 연구에서는 소형 동물의 두뇌를 자극하기 위한 완전 이식형 신경자극기가 개발되었다. 소형 동물의 전기자극은 전임상 연구, 신경과학 연구를 위한 행동연구 등에 활용된다. 특히, 자유롭게 움직이는 동물을 대상으로 한 행동 연구는 자극에 의한 감각 및 운동 기능의 조절을 관찰하는 데 유용하게 활용된다. 행동 연구는 두뇌의 특정 관심 영역을 직접적으로 자극하여 동물의 행동반응을 조건화하는 방식으로 수행된다. 이러한 적용을 가능케 하는 핵심기술은 이식형 신경자극기의 개발이다. 이식형 신경자극기는 동물의 움직임을 방해하지 않으면서도 그 행동을 조절하기 위해 사용된다. 따라서 동물 내에서의 안정적인 동작과 장치의 크기가 이식형 신경자극기를 설계함에 있어 중요한 문제이다. 기존의 신경자극기는 두뇌에 이식되는 전극 부분과, 동물의 등 부분에 위치한 회로부분으로 구성된다. 회로에서 생산된 전기자극은 회로와 전선으로 연결된 전극을 통해 목표 지점으로 전달된다. 장치는 배터리에 의해 구동되며, 내장된 마이크로 컨트롤러에 의해 제어된다. 이는 쉽고 간단한 접근방식이지만, 짧은 동작시간, 이식부위의 감염이나 장치의 기계적 결함, 그리고 동물의 자연스러운 움직임 방해 등 여러 문제점을 야기할 수 있다. 이러한 문제의 개선을 위해 무선통신이 가능하고, 저전력, 소형화된 완전 이식형 신경자극기의 설계가 필요하다. 본 연구에서는 자유롭게 움직이는 동물에 적용하기 위하여 원격 제어가 가능하며, 크기가 작고, 소모전력이 최소화된 완전이식형 자극기를 제시한다. 설계된 신경자극기는 목표로 하는 두뇌 영역에 접근할 수 있는 표면형 전극과 탐침형 전극, 그리고 자극 펄스 생성 회로를 포함하는 패키지 등의 모듈들로 구성되며, 각각의 모듈은 독립적으로 제작되어 동물에 이식된 뒤 케이블과 커넥터로 연결된다. 패키지 내부의 회로는 저전력 무선통신을 위한 지그비 트랜시버, 리튬 배터리의 재충전을 위한 인덕티브 링크, 그리고 신경자극을 위한 이상성 자극파형을 생성하는 ASIC으로 구성된다. 전력 절감을 위해 두 개의 모드를 통해 사용률을 조절하는 방식이 장치에 적용된다. 모든 모듈들은 이식 후의 생물학적, 화학적 안정성을 위해 액정 폴리머로 패키징되었다. 제작된 신경자극기를 평가하기 위해 무선 동작 테스트가 수행되었다. 지그비 통신의 신호 대 잡음비가 측정되었으며, 해당 통신의 동작거리 및 데이터 스트리밍 성능이 검사되었고, 장치의 충전이 수행될 때 코일간의 거리에 따라 전송되는 전력의 크기가 측정되었다. 장치의 평가 이후, 신경자극기는 쥐에 이식되었으며, 해당 동물은 이식된 장치를 이용해 방향 신호에 따라 좌우로 이동하도록 훈련되었다. 또한, 3차원 미로 구조에서 쥐의 이동방향을 유도하는 실험을 통하여 장치의 기능성을 추가적으로 검증하였다. 마지막으로, 제작된 장치의 특징이 여러 측면에서 심층적으로 논의되었다.Chapter 1 : Introduction 1 1.1. Neural Interface 2 1.1.1. Concept 2 1.1.2. Major Approaches 3 1.2. Neural Stimulator for Animal Brain Stimulation 5 1.2.1. Concept 5 1.2.2. Neural Stimulator for Freely Moving Small Animal 7 1.3. Suggested Approaches 8 1.3.1. Wireless Communication 8 1.3.2. Power Management 9 1.3.2.1. Wireless Power Transmission 10 1.3.2.2. Energy Harvesting 11 1.3.3. Full implantation 14 1.3.3.1. Polymer Packaging 14 1.3.3.2. Modular Configuration 16 1.4. Objectives of This Dissertation 16 Chapter 2 : Methods 18 2.1. Overview 19 2.1.1. Circuit Description 20 2.1.1.1. Pulse Generator ASIC 21 2.1.1.2. ZigBee Transceiver 23 2.1.1.3. Inductive Link 24 2.1.1.4. Energy Harvester 25 2.1.1.5. Surrounding Circuitries 26 2.1.2. Software Description 27 2.2. Antenna Design 29 2.2.1. RF Antenna 30 2.2.1.1. Design of Monopole Antenna 31 2.2.1.2. FEM Simulation 31 2.2.2. Inductive Link 36 2.2.2.1. Design of Coil Antenna 36 2.2.2.2. FEM Simulation 38 2.3. Device Fabrication 41 2.3.1. Circuit Assembly 41 2.3.2. Packaging 42 2.3.3. Electrode, Feedthrough, Cable, and Connector 43 2.4. Evaluations 45 2.4.1. Wireless Operation Test 46 2.4.1.1. Signal-to-Noise Ratio (SNR) Measurement 46 2.4.1.2. Communication Range Test 47 2.4.1.3. Device Operation Monitoring Test 48 2.4.2. Wireless Power Transmission 49 2.4.3. Electrochemical Measurements In Vitro 50 2.4.4. Animal Testing In Vivo 52 Chapter 3 : Results 57 3.1. Fabricated System 58 3.2. Wireless Operation Test 59 3.2.1. Signal-to-Noise Ratio Measurement 59 3.2.2. Communication Range Test 61 3.2.3. Device Operation Monitoring Test 62 3.3. Wireless Power Transmission 64 3.4. Electrochemical Measurements In Vitro 65 3.5. Animal Testing In Vivo 67 Chapter 4 : Discussion 73 4.1. Comparison with Conventional Devices 74 4.2. Safety of Device Operation 76 4.2.1. Safe Electrical Stimulation 76 4.2.2. Safe Wireless Power Transmission 80 4.3. Potential Applications 84 4.4. Opportunities for Further Improvements 86 4.4.1. Weight and Size 86 4.4.2. Long-Term Reliability 93 Chapter 5 : Conclusion 96 Reference 98 Appendix - Liquid Crystal Polymer (LCP) -Based Spinal Cord Stimulator 107 국문 초록 138 감사의 글 140Docto

A Subject-Specific Multiscale Model of Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a neuromodulation technique used to treat a variety of neurological disorders. While many types of neuromodulation therapy are invasive, TMS is an attractive alternative because it is noninvasive and has a very strong safety record. However, clinical use of TMS has preceded a thorough scientific understanding: its mechanisms of action remain elusive, and the spatial extent of modulation is not well understood. We created a subject-specific, multiscale computational model to gain insights into the physiological response during motor cortex TMS. Specifically, we developed an approach that integrates three main components: 1) a high-resolution anatomical MR image of the whole head with diffusion weighted MRI data; 2) a subject-specific, electromagnetic, non-homogeneous, anisotropic, finite element model of the whole head with a novel time-dependent solver; 3) a population of multicompartmental pyramidal cell neuron models. We validated the model predictions by comparing them to motor evoked potentials (MEPs) immediately following single-pulse TMS of the human motor cortex. This modeling approach contains several novel components, which in turn allowed us to gain greater insights into the interactions of TMS with the brain. Using this approach we found that electric field magnitudes within gray matter and white matter vary substantially with coil orientation. Our results suggest that 1) without a time-dependent, subject-specific, non-homogeneous, anisotropic model, loci of stimulation cannot be accurately predicted; 2) loci of stimulation depend upon biophysical properties and morphologies of pyramidal cells in both gray and white matter relative to the induced electric field. These results indicate that the extent of neuromodulation is more widespread than originally thought. Through medical imaging and computational modeling, we provide insights into the effects of TMS at a multiscale level, which would be unachievable by either method alone. Finally, our approach is amenable to clinical implementation. As a result, it could provide the means by which TMS parameters can be prescribed for treatment and a foundation for improving coil design

Integrated Circuits and Systems for Smart Sensory Applications

Connected intelligent sensing reshapes our society by empowering people with increasing new ways of mutual interactions. As integration technologies keep their scaling roadmap, the horizon of sensory applications is rapidly widening, thanks to myriad light-weight low-power or, in same cases even self-powered, smart devices with high-connectivity capabilities. CMOS integrated circuits technology is the best candidate to supply the required smartness and to pioneer these emerging sensory systems. As a result, new challenges are arising around the design of these integrated circuits and systems for sensory applications in terms of low-power edge computing, power management strategies, low-range wireless communications, integration with sensing devices. In this Special Issue recent advances in application-specific integrated circuits (ASIC) and systems for smart sensory applications in the following five emerging topics: (I) dedicated short-range communications transceivers; (II) digital smart sensors, (III) implantable neural interfaces, (IV) Power Management Strategies in wireless sensor nodes and (V) neuromorphic hardware