Wired, wireless and wearable bioinstrumentation for high-precision recording of bioelectrical signals in bidirectional neural interfaces

It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Furthermore, electrical stimulation of specific target brain regions has been shown to alleviate symptoms of neurological disorders, such as Parkinson’s disease, essential tremor, dystonia, epilepsy etc. In recent years, the traditional practice of continuously stimulating the brain using static stimulation parameters has shifted to the use of disease biomarkers to determine the intensity and timing of stimulation. The main motivation behind closed-loop stimulation is minimization of treatment side effects by providing only the necessary stimulation required within a certain period of time, as determined from a guiding biomarker. Hence, it is clear that high-quality recording of local field potentials (LFPs) or electrocorticographic (ECoG) signals during deep brain stimulation (DBS) is necessary to investigate the instantaneous brain response to stimulation, minimize time delays for closed-loop neurostimulation and maximise the available neural data. To our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording ECoG signals, which are of particular importance in closed-loop DBS and epilepsy DBS. In addition, existing recording systems lack the ability to provide artefact-free high-frequency (> 100 Hz) LFP recordings during DBS in real time primarily because of the contamination of the neural signals of interest by the stimulation artefacts. To address the problem of limited mobility often encountered by patients in the clinic and to provide a wide variety of high-precision sensor data to a closed-loop neurostimulation platform, a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless multi-instrument (55 × 80 mm2) was designed and developed. The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments. The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5 – 500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile tool to be utilized in a wide range of applications and environments. Moreover, in order to offer the capability of sensing and stimulating via the same electrode, novel real-time artefact suppression methods that could be used in bidirectional (recording and stimulation) system architectures are proposed and validated. More specifically, a novel, low-noise and versatile analog front-end (AFE), which uses a high-order (8th) analog Chebyshev notch filter to suppress the artefacts originating from the stimulation frequency, is presented. After defining the system requirements for concurrent LFP recording and DBS artefact suppression, the performance of the realised AFE is assessed by conducting both in vitro and in vivo experiments using unipolar and bipolar DBS (monophasic pulses, amplitude ranging from 3 to 6 V peak-to-peak, frequency 140 Hz and pulse width 100 µs). Under both in vitro and in vivo experimental conditions, the proposed AFE provided real-time, low-noise and artefact-free LFP recordings (in the frequency range 0.5 – 250 Hz) during stimulation. Finally, a family of tunable hardware filter designs and a novel method for real-time artefact suppression that enables wide-bandwidth biosignal recordings during stimulation are also presented. This work paves the way for the development of miniaturized research tools for closed-loop neuromodulation that use a wide variety of bioelectrical signals as control signals.Open Acces

A Biomechanical and Physiological Signal Monitoring System for Four Degrees of Upper Limb Movement

A lack of adherence to prescribed physical therapy regimens in improper healing results in poor outcomes for those affected by musculoskeletal disorders (MSDs) of the upper limb. Societal and psychological barriers to proper adherence can be addressed through the system presented in this work consisting of the following components: an ambulatory biosignal acquisition sleeve, an electromyography (EMG) based motion repetition detection algorithm, and the design of a compatible capacitive EMG acquisition module. The biosignal acquisition sleeve was untethered, unobtrusive to motion, contained only modular components, and collected biomechanical and physiological sensor data to form full motion profiles of the following four degrees of freedom: elbow flexion—extension, forearm pronation—supination, wrist flexion—extension, and ulnar--radial deviation. The piloted sleeve simultaneously collected data from four inertial sensors, two electromyography (EMG) sensors and a flex-bend sensor. A visualization application was developed to present the information in a manner meaningful to the user. As well, an EMG based motion repetition detector was developed for use within the system. It was validated using an existing database of 23 subjects with varying musculoskeletal health, achieving a success rate of 95.43%. This algorithm was modified for use with the sleeve, resulting in a 95% success rate. An electrode and analog front end module was proposed, relying on unique material structures and low-noise, precision sensing techniques. The system prototype presented a resource-conscious tool for multi-modality tracking of elbow, forearm, and wrist motion, which could eventually be integrated into upper limb MSD rehabilitation

Unsupervised Heart-rate Estimation in Wearables With Liquid States and A Probabilistic Readout

Heart-rate estimation is a fundamental feature of modern wearable devices. In this paper we propose a machine intelligent approach for heart-rate estimation from electrocardiogram (ECG) data collected using wearable devices. The novelty of our approach lies in (1) encoding spatio-temporal properties of ECG signals directly into spike train and using this to excite recurrently connected spiking neurons in a Liquid State Machine computation model; (2) a novel learning algorithm; and (3) an intelligently designed unsupervised readout based on Fuzzy c-Means clustering of spike responses from a subset of neurons (Liquid states), selected using particle swarm optimization. Our approach differs from existing works by learning directly from ECG signals (allowing personalization), without requiring costly data annotations. Additionally, our approach can be easily implemented on state-of-the-art spiking-based neuromorphic systems, offering high accuracy, yet significantly low energy footprint, leading to an extended battery life of wearable devices. We validated our approach with CARLsim, a GPU accelerated spiking neural network simulator modeling Izhikevich spiking neurons with Spike Timing Dependent Plasticity (STDP) and homeostatic scaling. A range of subjects are considered from in-house clinical trials and public ECG databases. Results show high accuracy and low energy footprint in heart-rate estimation across subjects with and without cardiac irregularities, signifying the strong potential of this approach to be integrated in future wearable devices.Comment: 51 pages, 12 figures, 6 tables, 95 references. Under submission at Elsevier Neural Network

e-SCP-ECG+ Protocol: An Expansion on SCP-ECG Protocol for Health Telemonitoring—Pilot Implementation

Standard Communication Protocol for Computer-assisted Electrocardiography (SCP-ECG) provides standardized communication among different ECG devices and medical information systems. This paper extends the use of this protocol in order to be included in health monitoring systems. It introduces new sections into SCP-ECG structure for transferring data for positioning, allergies, and five additional biosignals: noninvasive blood pressure (NiBP), body temperature (Temp), Carbon dioxide (CO2), blood oxygen saturation (SPO2), and pulse rate. It also introduces new tags in existing sections for transferring comprehensive demographic data. The proposed enhanced version is referred to as e-SCP-ECG+ protocol. This paper also considers the pilot implementation of the new protocol as a software component in a Health Telemonitoring System

Multimodal Wearable Sensors for Human-Machine Interfaces

Certain areas of the body, such as the hands, eyes and organs of speech production, provide high-bandwidth information channels from the conscious mind to the outside world. The objective of this research was to develop an innovative wearable sensor device that records signals from these areas more conveniently than has previously been possible, so that they can be harnessed for communication. A novel bioelectrical and biomechanical sensing device, the wearable endogenous biosignal sensor (WEBS), was developed and tested in various communication and clinical measurement applications. One ground-breaking feature of the WEBS system is that it digitises biopotentials almost at the point of measurement. Its electrode connects directly to a high-resolution analog-to-digital converter. A second major advance is that, unlike previous active biopotential electrodes, the WEBS electrode connects to a shared data bus, allowing a large or small number of them to work together with relatively few physical interconnections. Another unique feature is its ability to switch dynamically between recording and signal source modes. An accelerometer within the device captures real-time information about its physical movement, not only facilitating the measurement of biomechanical signals of interest, but also allowing motion artefacts in the bioelectrical signal to be detected. Each of these innovative features has potentially far-reaching implications in biopotential measurement, both in clinical recording and in other applications. Weighing under 0.45 g and being remarkably low-cost, the WEBS is ideally suited for integration into disposable electrodes. Several such devices can be combined to form an inexpensive digital body sensor network, with shorter set-up time than conventional equipment, more flexible topology, and fewer physical interconnections. One phase of this study evaluated areas of the body as communication channels. The throat was selected for detailed study since it yields a range of voluntarily controllable signals, including laryngeal vibrations and gross movements associated with vocal tract articulation. A WEBS device recorded these signals and several novel methods of human-to-machine communication were demonstrated. To evaluate the performance of the WEBS system, recordings were validated against a high-end biopotential recording system for a number of biopotential signal types. To demonstrate an application for use by a clinician, the WEBS system was used to record 12‑lead electrocardiogram with augmented mechanical movement information

대규모 인구 모델과 단일 가슴 착용형 장치를 활용한 비침습적 연속 동맥 혈압 모니터링 시스템

학위논문 (박사) -- 서울대학교 대학원 : 공과대학 협동과정 바이오엔지니어링전공, 2021. 2. 김희찬.최근 수십 년 동안 비침습적 연속 혈압 모니터링에 대한 필요성이 점차 대두되면서 맥파 전달 시간, 맥파 도달 시간, 또는 광용적맥파의 파형으로부터 추출된 다양한 특징들을 이용한 혈압 추정 연구들이 전세계적으로 활발하게 진행되었다. 하지만 대부분의 연구들은 국제 혈압 표준을 만족시키지 못하는 매우 적은 수의 피험자들 만을 대상으로 주로 혈압 추정 모델을 개발 및 검증하였기 때문에 성능의 정확도가 적절하게 검증되지 못했다는 한계점이 있었고, 또한 혈압 추정 파라미터 추출을 위한 생체 신호들을 측정하기 위해 대부분 두 개 이상의 모듈을 필요로 하면서 실용성 측면에서 한계점이 있었다. 첫 번째 연구는 대규모 생체신호 데이터베이스들을 분석함으로써 임상적으로 허용 가능한 수준의 정확도가 적절히 검증된 혈압 추정 모델을 개발하는 것을 목적으로 진행되었다. 본 연구에서는 1376명의 수술 중 환자들의 약 250만 심박 주기에 대해 측정된 두 가지 비침습적 생체신호인 심전도와 광용적맥파를 활용한 혈압 추정 방식들을 분석하였다. 맥파 도달 시간, 심박수, 그리고 다양한 광용적맥파 파형 피처들을 포함하는 총 42 종류의 파라미터들을 대상으로 피처 선택 기법들을 적용한 결과, 28개의 피처들이 혈압 추정 파라미터로 결정되었고, 특히 두 가지 광용적맥파 피처들이 기존에 혈압 추정 파라미터로 가장 주요하게 활용되었던 맥파 도달 시간보다 우월한 파라미터들로 분석되었다. 선정된 파라미터들을 활용하여 혈압의 낮은 주파수 성분을 인공신경망으로 모델링하고, 높은 주파수 성분을 순환신경망으로 모델링 한 결과, 수축기 혈압 에러율 0.05 ± 6.92 mmHg와 이완기 혈압 에러율 -0.05 ± 3.99 mmHg 정도의 높은 정확도를 달성하였다. 또 다른 생체신호 데이터베이스에서 추출한 334명의 중환자들을 대상으로 모델을 외부 검증했을 때 유사한 결과를 획득하면서 세 가지 대표적 혈압 측정 장비 기준들을 모두 만족시켰다. 해당 결과를 통해 제안된 혈압 추정 모델이 1000명 이상의 다양한 피험자들을 대상으로 적용 가능함을 확인하였다. 두 번째 연구는 일상 생활 중 장기간 모니터링이 가능한 단일 착용형 혈압 모니터링 시스템을 개발하는 것을 목적으로 진행되었다. 대부분의 기존 혈압 추정 연구들은 혈압 추정 파라미터 추출을 위해 필요한 생체신호들을 측정하기 위해 두 군데 이상의 신체 지점에 두 개 이상의 모듈을 부착하는 등 실용성 측면에서 한계를 나타냈다. 이를 해결하기 위해 본 연구에서는 심전도와 광용적맥파를 동시에 연속적으로 측정하는 단일 가슴 착용형 디바이스를 개발하였고, 개발된 디바이스를 대상으로 총 25명의 건강한 피험자들로부터 데이터를 획득하였다. 손가락에서 측정된 광용적맥파와 가슴에서 측정된 광용적맥파 간 파형의 특성에 유의미한 차이가 있기 때문에 가슴에서 측정된 광용적맥파에서 추출된 피처들을 대응되는 손가락에서 측정된 광용적맥파 피처들로 특성을 변환하는 전달 함수 모델을 개발하였다. 25명으로부터 획득한 데이터에 전달 함수 모델을 적용시킨 후 혈압 추정 모델을 검증한 결과, 수축기 혈압 에러율 0.54 ± 7.47 mmHg와 이완기 혈압 에러율 0.29 ± 4.33 mmHg로 나타나면서 세 가지 혈압 측정 장비 기준들을 모두 만족시켰다. 결론적으로 본 연구에서는 임상적으로 허용 가능한 수준의 정확도로 장기간 일상 생활이 가능한 비침습적 연속 동맥 혈압 모니터링 시스템을 개발하고 다수의 데이터셋을 대상으로 검증함으로써 고혈압 조기 진단 및 예방을 위한 모바일 헬스케어 서비스의 가능성을 확인하였다.As non-invasive continuous blood pressure monitoring (NCBPM) has gained wide attraction in the recent decades, many studies on blood pressure (BP) estimation using pulse transit time (PTT), pulse arrival time (PAT), and characteristics extracted from the morphology of photoplethysmogram (PPG) waveform as indicators of BP have been conducted. However, most of the studies have used small homogeneous subject pools to generate models of BP, which led to inconsistent results in terms of accuracy. Furthermore, the previously proposed modalities to measure BP indicators are questionable in terms of practicality, and lack the potential for being utilized in daily life. The first goal of this thesis is to develop a BP estimation model with clinically valid accuracy using a large pool of heterogeneous subjects undergoing various surgeries. This study presents analyses of BP estimation methods using 2.4 million cardiac cycles of two commonly used non-invasive biosignals, electrocardiogram (ECG) and PPG, from 1376 surgical patients. Feature selection methods were used to determine the best subset of predictors from a total of 42 including PAT, heart rate, and various PPG morphology features. BP estimation models were constructed using linear regression, random forest, artificial neural network (ANN), and recurrent neural network (RNN), and the performances were evaluated. 28 features out of 42 were determined as suitable for BP estimation, in particular two PPG morphology features outperformed PAT, which has been conventionally seen as the best non-invasive indicator of BP. By modelling the low frequency component of BP using ANN and the high frequency component using RNN with the selected predictors, mean errors of 0.05 ± 6.92 mmHg for systolic blood pressure (SBP), and -0.05 ± 3.99 mmHg for diastolic blood pressure (DBP) were achieved. External validation of the model using another biosignal database consisting of 334 intensive care unit patients led to similar results, satisfying three international standards concerning the accuracy of BP monitors. The results indicate that the proposed method can be applied to large number of subjects and various subject phenotypes. The second goal of this thesis is to develop a wearable BP monitoring system, which facilitates NCBPM in daily life. Most previous studies used two or more modules with bulky electrodes to measure biosignals such as ECG and PPG for extracting BP indicators. In this study, a single wireless chest-worn device measuring ECG and PPG simultaneously was developed. Biosignal data from 25 healthy subjects measured by the developed device were acquired, and the BP estimation model developed above was tested on this data after applying a transfer function mapping the chest PPG morphology features to the corresponding finger PPG morphology features. The model yielded mean errors of 0.54 ± 7.47 mmHg for SBP, and 0.29 ± 4.33 mmHg for DBP, again satisfying the three standards for the accuracy of BP monitors. The results indicate that the proposed system can be a stepping stone to the realization of mobile NCBPM in daily life. In conclusion, the clinical validity of the proposed system was checked in three different datasets, and it is a practical solution to NCBPM due to its non-occlusive form as a single wearable device.Abstract i Contents iv List of Tables vii List of Figures viii Chapter 1 General Introduction 1 1.1 Need for Non-invasive Continuous Blood Pressure Monitoring (NCBPM) 2 1.2 Previous Studies for NCBPM 5 1.3 Issues with Previous Studies 9 1.4 Thesis Objectives 12 Chapter 2 Non-invasive Continuous Arterial Blood Pressure Estimation Model in Large Population 14 2.1 Introduction 15 2.1.1 Electrocardiogram (ECG) and Photoplethysmogram (PPG) Features for Blood Pressure (BP) Estimation 15 2.1.2 Description of Surgical Biosignal Databases 16 2.2 Feature Analysis 19 2.2.1 Data Acquisition and Data Pre-processing 19 2.2.2 Feature Extraction 25 2.2.3 Feature Selection 35 2.3 Construction of the BP Estimation Models 44 2.3.1 Frequency Component Separation 44 2.3.2 Modelling Algorithms 47 2.3.3 Summary of Training and Validation 52 2.4 Results and Discussion 54 2.4.1 Feature Analysis 54 2.4.1.1 Pulse Arrival Time versus Pulse Transit Time 54 2.4.1.2 Feature Selection 57 2.4.2 Optimization of the BP Estimation Models 63 2.4.2.1 Frequency Component Separation 63 2.4.2.2 Modelling Algorithms 66 2.4.2.3 Comparison against Different Modelling Settings 68 2.4.3 Performance of the Best-case BP Estimation Model 69 2.4.4 Limitations 75 2.5 Conclusion 78 Chapter 3 Development of the Single Chest-worn Device for Non-invasive Continuous Arterial Blood Pressure Monitoring 80 3.1 Introduction 81 3.2 Development of the Single Chest-worn Device 84 3.2.1 Hardware Development 84 3.2.2 Software Development 90 3.2.3 Clinical Trial 92 3.3 Development of the Transfer Function 95 3.3.1 Finger PPG versus Chest PPG 95 3.3.2 The Concept of the Transfer Function 97 3.3.3 Data Acquisition for Modelling of the Transfer Function 98 3.4 Results and Discussion 100 3.4.1 Construction of the Transfer Function 100 3.4.2 Test of the BP Estimation Model 101 3.4.3 Comparison with the Previous Study using the Single Chest-worn Device 104 3.4.4 Limitations 106 3.5 Conclusion 108 Chapter 4 Thesis Summary and Future Direction 109 4.1 Summary and Contributions 110 4.2 Future Work 113 Bibliography 115 Abstract in Korean 129 Acknowledgement 132Docto

Amplifiers in Biomedical Engineering: A Review from Application Perspectives

Continuous monitoring and treatment of various diseases with biomedical technologies and wearable electronics has become significantly important. The healthcare area is an important, evolving field that, among other things, requires electronic and micro-electromechanical technologies. Designed circuits and smart devices can lead to reduced hospitalization time and hospitals equipped with high-quality equipment. Some of these devices can also be implanted inside the body. Recently, various implanted electronic devices for monitoring and diagnosing diseases have been presented. These instruments require communication links through wireless technologies. In the transmitters of these devices, power amplifiers are the most important components and their performance plays important roles. This paper is devoted to collecting and providing a comprehensive review on the various designed implanted amplifiers for advanced biomedical applications. The reported amplifiers vary with respect to the class/type of amplifier, implemented CMOS technology, frequency band, output power, and the overall efficiency of the designs. The purpose of the authors is to provide a general view of the available solutions, and any researcher can obtain suitable circuit designs that can be selected for their problem by reading this survey

Double-Differential Amplifier for sEMG Measurement by Means of a Current-Mode Approach

This work proposes a Double Differential (DD) amplifier topology which exploits the advantages of the current-mode approach. DD amplifiers are useful as front-ends in standalone active electrodes for superficial electromyography (sEMG) wearable applications and electroneurography (ENG) measurement devices. Front-ends for these applications need to attain low noise, high common-mode rejection ratio, and high input impedance to measure biopotential signals and can further benefit from low power operation, a small size, and an easily adaptable output. Presently published DD amplifiers are either complex in terms of a high part count, leading to higher power consumption and size, or suffer from limited interference-rejection capabilities and require further analog processing for compatibility with single-ended systems. Therefore, in this work, second-generation current conveyors have been leveraged to obtain a simple topology combining a small active-part count, a high common-mode rejection ratio, and a flexible output stage. The current-mode DD amplifier is presented and analyzed in detail to estimate its parameters and model the effects of nonidealities in the circuit. In order to validate the proposed topology, a discrete-component implementation was realized as a proof-of-concept. The results experimentally demonstrated the properties of the proposed topology and its feasibility for measuring superficial sEMG DD signals.Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señale

Decentralized Federated Learning for Epileptic Seizures Detection in Low-Power Wearable Systems

In healthcare, data privacy of patients regulations prohibits data from being moved outside the hospital, preventing international medical datasets from being centralized for AI training. Federated learning (FL) is a data privacy-focused method that trains a global model by aggregating local models from hospitals. Existing FL techniques adopt a central server-based network topology, where the server assembles the local models trained in each hospital to create a global model. However, the server could be a point of failure, and models trained in FL usually have worse performance than those trained in the centralized learning manner when the patient's data are not independent and identically distributed (Non-IID) in the hospitals. This paper presents a decentralized FL framework, including training with adaptive ensemble learning and a deployment phase using knowledge distillation. The adaptive ensemble learning step in the training phase leads to the acquisition of a specific model for each hospital that is the optimal combination of local models and models from other available hospitals. This step solves the non-IID challenges in each hospital. The deployment phase adjusts the model's complexity to meet the resource constraints of wearable systems. We evaluated the performance of our approach on edge computing platforms using EPILEPSIAE and TUSZ databases, which are public epilepsy datasets.RYC2021-032853-