Multimodal Photoplethysmography-Based Approaches for Improved Detection of Hypertension

Elevated blood pressure (BP) is a major cause of death, yet hypertension commonly goes undetected. Owing to its nature, it is typically asymptomatic until later in its progression when the vessel or organ structure has already been compromised. Therefore, noninvasive and continuous BP measurement methods are needed to ensure appropriate diagnosis and early management before hypertension leads to irreversible complications. Photoplethysmography (PPG) is a noninvasive technology with waveform morphologies similar to that of arterial BP waveforms, therefore attracting interest regarding its usability in BP estimation. In recent years, wearable devices incorporating PPG sensors have been proposed to improve the early diagnosis and management of hypertension. Additionally, the need for improved accuracy and convenience has led to the development of devices that incorporate multiple different biosignals with PPG. Through the addition of modalities such as an electrocardiogram, a final measure of the pulse wave velocity is derived, which has been proved to be inversely correlated to BP and to yield accurate estimations. This paper reviews and summarizes recent studies within the period 2010-2019 that combined PPG with other biosignals and offers perspectives on the strengths and weaknesses of current developments to guide future advancements in BP measurement. Our literature review reveals promising measurement accuracies and we comment on the effective combinations of modalities and success of this technology

Assessment Of Blood Pressure Regulatory Controls To Detect Hypovolemia And Orthostatic Intolerance

Regulation of blood pressure is vital for maintaining organ perfusion and homeostasis. A significant decline in arterial blood pressure could lead to fainting and hypovolemic shock. In contrast to young and healthy, people with impaired autonomic control due to aging or disease find regulating blood pressure rather demanding during orthostatic challenge. This thesis performed an assessment of blood pressure regulatory controls during orthostatic challenge via traditional as well as novel approaches with two distinct applications 1) to design a robust automated system for early identification of hypovolemia and 2) to assess orthostatic tolerance in humans. In chapter 3, moderate intensity hemorrhage was simulated via lower-body negative pressure (LBNP) with an aim to identify moderate intensity hemorrhage (-30 and -40 mmHg LBNP) from resting baseline. Utilizing features extracted from common vital sign monitors, a classification accuracy of 82% and 91% was achieved for differentiating -30 and -40 mmHg LBNP, respectively from baseline. In chapter 4, cause-and-effect relationship between the representative signals of the cardiovascular and postural systems to ascertain blood pressure homeostasis during standing was performed. The degree of causal interaction between the two systems, studied via convergent cross mapping (CCM), showcased the existence of a significant bi-directional interaction between the representative signals of two systems to regulate blood pressure. Therefore, the two systems should be accounted for jointly when addressing physiology behind fall. Further, in chapter 5, the potential of artificial gravity (2-g) induced via short-arm human centrifuge at feet towards evoking blood pressure regulatory controls analogous to standing was investigated. The observation of no difference in the blood pressure regulatory controls, during 2-g centrifugation compared to standing, strongly supported the hypothesis of artificial hypergravity for mitigating cardiovascular deconditioning, hence minimizing post-flight orthostatic intolerance

A unified methodology for heartbeats detection in seismocardiogram and ballistocardiogram signals

This work presents a methodology to analyze and segment both seismocardiogram (SCG) and ballistocardiogram (BCG) signals in a unified fashion. An unsupervised approach is followed to extract a template of SCG/BCG heartbeats, which is then used to fine-tune temporal waveform annotation. Rigorous performance assessment is conducted in terms of sensitivity, precision, Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) of annotation. The methodology is tested on four independent datasets, covering different measurement setups and time resolutions. A wide application range is therefore explored, which better characterizes the robustness and generality of the method with respect to a single dataset. Overall, sensitivity and precision scores are uniform across all datasets (p > 0.05 from the Kruskal–Wallis test): the average sensitivity among datasets is 98.7%, with 98.2% precision. On the other hand, a slight yet significant difference in RMSE and MAE scores was found (p < 0.01) in favor of datasets with higher sampling frequency. The best RMSE scores for SCG and BCG are 4.5 and 4.8 ms, respectively; similarly, the best MAE scores are 3.3 and 3.6 ms. The results were compared to relevant recent literature and are found to improve both detection performance and temporal annotation errors

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

Non-linear Heart Rate and Blood Pressure Interaction in Response to Lower-Body Negative Pressure

Early detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP) from 0 to -40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate (i.e., baroreflex response) is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG) signals were acquired simultaneously from young, healthy participants (27 ± 1 years, N = 27) during each LBNP stage, from which heart rate (represented by RR interval), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were derived. The heart rate and blood pressure causal interaction (RR SBP and RR MAP) was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR SBP and RR MAP) showed a significantly (p \u3c 0.001) higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP RR and MAP RR). In response to moderate category hemorrhage (-30 mmHg LBNP), no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10) along with the RR SBP (p = 0.76), RR MAP (p = 0.60), and SBP RR (p = 0.07) causality compared to the resting stage. Contrarily, a significant elevation in the MAP RR (p = 0.004) causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP RR) of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from the resting stage. Therefore, monitoring baroreflex causality can have a clinical utility in making triage decisions to impede hemorrhage progression

Characterization, Classification, and Genesis of Seismocardiographic Signals

Seismocardiographic (SCG) signals are the acoustic and vibration induced by cardiac activity measured non-invasively at the chest surface. These signals may offer a method for diagnosing and monitoring heart function. Successful classification of SCG signals in health and disease depends on accurate signal characterization and feature extraction. In this study, SCG signal features were extracted in the time, frequency, and time-frequency domains. Different methods for estimating time-frequency features of SCG were investigated. Results suggested that the polynomial chirplet transform outperformed wavelet and short time Fourier transforms. Many factors may contribute to increasing intrasubject SCG variability including subject posture and respiratory phase. In this study, the effect of respiration on SCG signal variability was investigated. Results suggested that SCG waveforms can vary with lung volume, respiratory flow direction, or a combination of these criteria. SCG events were classified into groups belonging to these different respiration phases using classifiers, including artificial neural networks, support vector machines, and random forest. Categorizing SCG events into different groups containing similar events allows more accurate estimation of SCG features. SCG feature points were also identified from simultaneous measurements of SCG and other well-known physiologic signals including electrocardiography, phonocardiography, and echocardiography. Future work may use this information to get more insights into the genesis of SCG

Enabling Wearable Hemodynamic Monitoring Using Multimodal Cardiomechanical Sensing Systems

Hemodynamic parameters such as blood pressure and stroke volume are instrumental to understanding the pathogenesis of cardiovascular disease. Unfortunately, the monitoring of these hemodynamic parameters is still limited to in-clinic measurements and cumbersome hardware precludes convenient, ubiquitous use. To address this burden, in this work, we explore seismocardiogram-based wearable multimodal sensing techniques to estimate blood pressure and stroke volume. First, the performance of a multimodal, wrist-worn device capable of obtaining noninvasive pulse transit time measurements is used to estimate blood pressure in an unsupervised, at-home setting. Second, the feasibility of this wrist-worn device is comprehensively evaluated in a diverse and medically underserved population over the course of several perturbations used to modulate blood pressure through different pathways. Finally, the ability of wearable signals—acquired from a custom chest-worn biosensor—to noninvasively quantify stroke volume in patients with congenital heart disease is examined in a hospital setting. Collectively, this work demonstrates the advancements necessary towards enabling noninvasive, longitudinal, and accurate measurements of these hemodynamic parameters in remote settings, which offers to improve health equity and disease monitoring in low-resource settings.Ph.D

Wearable and Nearable Biosensors and Systems for Healthcare

Biosensors and systems in the form of wearables and “nearables” (i.e., everyday sensorized objects with transmitting capabilities such as smartphones) are rapidly evolving for use in healthcare. Unlike conventional approaches, these technologies can enable seamless or on-demand physiological monitoring, anytime and anywhere. Such monitoring can help transform healthcare from the current reactive, one-size-fits-all, hospital-centered approach into a future proactive, personalized, decentralized structure. Wearable and nearable biosensors and systems have been made possible through integrated innovations in sensor design, electronics, data transmission, power management, and signal processing. Although much progress has been made in this field, many open challenges for the scientific community remain, especially for those applications requiring high accuracy. This book contains the 12 papers that constituted a recent Special Issue of Sensors sharing the same title. The aim of the initiative was to provide a collection of state-of-the-art investigations on wearables and nearables, in order to stimulate technological advances and the use of the technology to benefit healthcare. The topics covered by the book offer both depth and breadth pertaining to wearable and nearable technology. They include new biosensors and data transmission techniques, studies on accelerometers, signal processing, and cardiovascular monitoring, clinical applications, and validation of commercial devices