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    ๋”ฅ๋Ÿฌ๋‹ ๊ธฐ๋ฐ˜ ํ˜ˆ์•• ์˜ˆ์ธก ๊ธฐ๋ฒ•

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ) -- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ๊ณต๊ณผ๋Œ€ํ•™ ์ „๊ธฐยท์ •๋ณด๊ณตํ•™๋ถ€, 2020. 8. ์œค์„ฑ๋กœ.While COVID-19 is changing the world's social profile, it is expected that the telemedicine sector, which has not been activated due to low regulation and reliability, will also undergo a major change. As COVID-19 spreads in the United States, the US Department of Health \& Human Services temporarily loosens the standards for telemedicine, while enabling telemedicine using Facebook, Facebook Messenger-based video chat, Hangouts, and Skype. The expansion of the telemedicine market is expected to quickly transform the existing treatment-oriented hospital-led medical market into a digital healthcare service market focused on prevention and management through wearables, big data, and health records analysis. In this prevention and management-oriented digital healthcare service, it is very important to develop a technology that can easily monitor a person's health status. One of the vital signs that can be used for personal health monitoring is blood pressure. High BP is a common and dangerous condition. About 1 out of 3 adults in the U.S. (about 75 million people) have high BP. This common condition increases the risk of heart disease and stroke, two of the leading causes of death for Americans. High BP is called the silent killer because it often has no warning signs or symptoms, and many people are not aware they have it. For these reasons, it is important to develop a technology that can easily and conveniently check BP regularly. In biomedical data analysis, various studies are being attempted to effectively analyze by applying machine learning to biomedical big data accumulated in large quantities. However, collecting blood pressure-related data at the level of big data is very difficult and very expensive because it takes a lot of manpower and time. So in this dissertation, we proposed a three-step strategy to overcome these issues. First, we describe a BP prediction model with extraction and concentration CNN architecture, to process publicly disclosed sequential ECG and PPG dataset. Second, we evaluate the performance of the developed model by applying the developed model to privately measured data. To address the third issue, we propose the knowledge distillation method and input pre-processing method to improve the accuracy of the blood pressure prediction model. All the methods proposed in this dissertation are based on a deep convolutional neural network (CNN). Unlike other studies based on manual recognition of the features, by utilizing the advantage of deep learning which automatically extracts features, raw biomedical signals are used intact to reflect the inherent characteristics of the signals themselves.์ฝ”๋กœ๋‚˜ 19์— ์˜ํ•œ ์ „ ์„ธ๊ณ„์˜ ์‚ฌํšŒ์  ํ”„๋กœํ•„ ๋ณ€ํ™”๋กœ, ๊ทœ์ œ์™€ ์‹ ๋ขฐ์„ฑ์ด ๋‚ฎ๊ธฐ ๋•Œ๋ฌธ์— ํ™œ์„ฑํ™” ๋˜์ง€ ์•Š์€ ์›๊ฒฉ ์˜๋ฃŒ ๋ถ„์•ผ๋„ ํฐ ๋ณ€ํ™”๋ฅผ ๊ฒช์„ ๊ฒƒ์œผ๋กœ ์˜ˆ์ƒ๋ฉ๋‹ˆ๋‹ค. ์ฝ”๋กœ๋‚˜ 19๊ฐ€ ๋ฏธ๊ตญ์— ํผ์ง์— ๋”ฐ๋ผ ๋ฏธ๊ตญ ๋ณด๊ฑด๋ณต์ง€๋ถ€๋Š” ์›๊ฒฉ ์ง„๋ฃŒ์˜ ํ‘œ์ค€์„ ์ผ์‹œ์ ์œผ๋กœ ์™„ํ™”ํ•˜๋ฉด์„œ ํŽ˜์ด์Šค๋ถ, ํŽ˜์ด์Šค๋ถ ๋ฉ”์‹ ์ € ๊ธฐ๋ฐ˜ ํ™”์ƒ ์ฑ„ํŒ…, ํ–‰์•„์›ƒ, ์Šค์นด์ดํ”„๋ฅผ ์‚ฌ์šฉํ•œ ์›๊ฒฉ ์ง„๋ฃŒ๋ฅผ ๊ฐ€๋Šฅํ•˜๊ฒŒ ํ–ˆ์Šต๋‹ˆ๋‹ค. ์›๊ฒฉ์˜๋ฃŒ ์‹œ์žฅ์˜ ํ™•์žฅ์€ ๊ธฐ์กด์˜ ์น˜๋ฃŒ์ค‘์‹ฌ ๋ณ‘์›์ฃผ๋„์˜ ์˜๋ฃŒ์‹œ์žฅ์„ ์›จ์–ด๋Ÿฌ๋ธ”, ๋น… ๋ฐ์ดํ„ฐ ๋ฐ ๊ฑด๊ฐ•๊ธฐ๋ก ๋ถ„์„์„ ํ†ตํ•œ ์˜ˆ๋ฐฉ ๋ฐ ๊ด€๋ฆฌ์— ์ค‘์ ์„ ๋‘” ๋””์ง€ํ„ธ ์˜๋ฃŒ ์„œ๋น„์Šค ์‹œ์žฅ์œผ๋กœ ๋น ๋ฅด๊ฒŒ ๋ณ€ํ™”์‹œํ‚ฌ ๊ฒƒ์œผ๋กœ ์˜ˆ์ƒ๋ฉ๋‹ˆ๋‹ค. ์ด๋Ÿฌํ•œ ์˜ˆ๋ฐฉ ๋ฐ ๊ด€๋ฆฌ ์ค‘์‹ฌ์˜ ๋””์ง€ํ„ธ ํ—ฌ์Šค์ผ€์–ด ์„œ๋น„์Šค์—์„œ๋Š” ์‚ฌ๋žŒ์˜ ๊ฑด๊ฐ• ์ƒํƒœ๋ฅผ ์‰ฝ๊ฒŒ ๋ชจ๋‹ˆํ„ฐ๋ง ํ•  ์ˆ˜ ์žˆ๋Š” ๊ธฐ์ˆ  ๊ฐœ๋ฐœ์ด ๋งค์šฐ ์ค‘์š”ํ•œ๋ฐ ํ˜ˆ์••์€ ๊ฐœ์ธ ๊ฑด๊ฐ• ๋ชจ๋‹ˆํ„ฐ๋ง์— ์‚ฌ์šฉ๋  ์ˆ˜ ์žˆ๋Š” ํ•„์ˆ˜ ์ง•ํ›„ ์ค‘ ํ•˜๋‚˜ ์ž…๋‹ˆ๋‹ค. ๊ณ ํ˜ˆ์••์€ ์•„์ฃผ ํ”ํ•˜๊ณ  ์œ„ํ—˜ํ•œ ์งˆํ™˜์ž…๋‹ˆ๋‹ค. ๋ฏธ๊ตญ ์„ฑ์ธ 3๋ช…์ค‘ 1๋ช…(์•ฝ 7,500๋งŒ๋ช…)์ด ๊ณ ํ˜ˆ์••์„ ๊ฐ€์ง€๊ณ  ์žˆ์Šต๋‹ˆ๋‹ค. ์ด๋Š” ๋ฏธ๊ตญ์ธ์˜ ์ฃผ์š” ์‚ฌ๋ง ์›์ธ ์ค‘ ๋‘๊ฐ€์ง€์ธ ์‹ฌ์žฅ์งˆํ™˜๊ณผ ๋‡Œ์กธ์ค‘์˜ ์œ„ํ—˜์„ ์ฆ๊ฐ€ ์‹œํ‚ต๋‹ˆ๋‹ค. ๊ณ ํ˜ˆ์••์€ ์‹ ์ฒด์— ๊ฒฝ๊ณ  ์‹ ํ˜ธ๋‚˜ ์ž๊ฐ ์ฆ์ƒ์ด ์—†์–ด ๋งŽ์€ ์‚ฌ๋žŒ๋“ค์ด ์ž์‹ ์ด ๊ณ ํ˜ˆ์••์ธ ๊ฒƒ์„ ์ธ์ง€ํ•˜์ง€ ๋ชปํ•˜๊ธฐ ๋•Œ๋ฌธ์— "์‚ฌ์ผ๋ŸฐํŠธ ํ‚ฌ๋Ÿฌ"๋ผ ๋ถˆ๋ฆฌ์›๋‹ˆ๋‹ค. ์ด๋Ÿฌํ•œ ์ด์œ ๋กœ ์ •๊ธฐ์ ์œผ๋กœ ์‰ฝ๊ณ  ํŽธ๋ฆฌํ•˜๊ฒŒ ํ˜ˆ์••์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ๋Š” ๊ธฐ์ˆ ์˜ ๊ฐœ๋ฐœ์ด ๋งค์šฐ ์ค‘์š”ํ•ฉ๋‹ˆ๋‹ค. ์ƒ์ฒด์˜ํ•™ ๋ฐ์ดํ„ฐ ๋ถ„์„ ๋ถ„์•ผ์—์„œ๋Š” ๋จธ์‹  ๋Ÿฌ๋‹์„ ๋Œ€๋Ÿ‰์œผ๋กœ ์ˆ˜์ง‘๋œ ์ƒ์ฒด์˜ํ•™ ๋น… ๋ฐ์ดํ„ฐ์— ์ ์šฉํ•˜๋Š” ๋‹ค์–‘ํ•œ ์—ฐ๊ตฌ๊ฐ€ ํšจ๊ณผ์ ์œผ๋กœ ์ด๋ฃจ์–ด์ง€๊ณ  ์žˆ์Šต๋‹ˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๋น… ๋ฐ์ดํ„ฐ ์ˆ˜์ค€์œผ๋กœ ๋‹ค๋Ÿ‰์˜ ํ˜ˆ์•• ๊ด€๋ จ ๋ฐ์ดํ„ฐ๋ฅผ ์ˆ˜์ง‘ํ•˜๋Š” ๊ฒƒ์€ ๋งŽ์€ ์ „๋ฌธ์ ์ธ ์ธ๋ ฅ๋“ค์ด ์˜ค๋žœ์‹œ๊ฐ„์„ ํ•„์š”๋กœ ํ•˜๊ธฐ ๋•Œ๋ฌธ์— ๋งค์šฐ ์–ด๋ ต๊ณ  ๋น„์šฉ ๋˜ํ•œ ๋งŽ์ด ํ•„์š”ํ•ฉ๋‹ˆ๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ํ•™์œ„๋…ผ๋ฌธ์—์„œ๋Š” ์ด๋Ÿฌํ•œ ๋ฌธ์ œ๋ฅผ ๊ทน๋ณตํ•˜๊ธฐ ์œ„ํ•œ 3๋‹จ๊ณ„ ์ „๋žต์„ ์ œ์•ˆํ–ˆ์Šต๋‹ˆ๋‹ค. ๋จผ์ € ๋ˆ„๊ตฌ๋‚˜ ์‹œ์šฉํ•  ์ˆ˜ ์žˆ๋„๋ก ๊ณต๊ฐœ๋˜์–ด ์žˆ๋Š” ์‹ฌ์ „๋„, ๊ด‘์šฉ์ ๋งฅํŒŒ ๋ฐ์ดํ„ฐ์…‹์„ ์ด์šฉ, ์ˆœ์ฐจ์ ์ธ ์‹ฌ์ „๋„, ๊ด‘์šฉ์ ๋งฅํŒŒ ์‹ ํ˜ธ์—์„œ ํ˜ˆ์••์„ ์ž˜ ์˜ˆ์ธกํ•˜๋„๋ก ๊ณ ์•ˆ๋œ ์ถ”์ถœ ๋ฐ ๋†์ถ• ์ž‘์—…์„ ๋ฐ˜๋ณตํ•˜๋Š” ํ•จ์„ฑ๊ณฑ ์‹ ๊ฒฝ๋ง ๊ตฌ์กฐ๋ฅผ ์ œ์•ˆํ–ˆ์Šต๋‹ˆ๋‹ค. ๋‘๋ฒˆ์งธ๋กœ ์ œ์•ˆ๋œ ํ•ฉ์„ฑ๊ณฑ ์‹ ๊ฒฝ๋ง ๋ชจ๋ธ์„ ๊ฐœ์ธ์—๊ฒŒ์„œ ์ธก์ •ํ•œ ๊ด‘์šฉ์ ๋งฅํŒŒ ์‹ ํ˜ธ๋ฅผ ์ด์šฉํ•ด ์ œ์•ˆ๋œ ํ•จ์„ฑ๊ณฑ ์‹ ๊ฒฝ๋ง ๋ชจ๋ธ์˜ ์„ฑ๋Šฅ์„ ํ‰๊ฐ€ํ–ˆ์Šต๋‹ˆ๋‹ค. ์„ธ๋ฒˆ์งธ๋กœ ํ˜ˆ์••์˜ˆ์ธก ๋ชจ๋ธ์˜ ์ •ํ™•์„ฑ์„ ๋†’์ด๊ธฐ ์œ„ํ•ด ์ง€์‹ ์ฆ๋ฅ˜๋ฒ•๊ณผ ์ž…๋ ฅ์‹ ํ˜ธ ์ „์ฒ˜๋ฆฌ ๋ฐฉ๋ฒ•์„ ์ œ์•ˆํ–ˆ์Šต๋‹ˆ๋‹ค. ์ด ๋…ผ๋ฌธ์—์„œ ์ œ์•ˆ๋œ ๋ชจ๋“  ํ˜ˆ์••์˜ˆ์ธก ๋ฐฉ๋ฒ•์€ ํ•ฉ์„ฑ๊ณฑ ์‹ ๊ฒฝ๋ง์„ ๊ธฐ๋ฐ˜์œผ๋กœ ํ•ฉ๋‹ˆ๋‹ค. ํ˜ˆ์•• ์˜ˆ์ธก์— ํ•„์š”ํ•œ ํŠน์ง•๋“ค์„ ์ˆ˜๋™์œผ๋กœ ์ถ”์ถœํ•ด์•ผ ํ•˜๋Š” ๋‹ค๋ฅธ ์—ฐ๊ตฌ๋“ค๊ณผ ๋‹ค๋ฅด๊ฒŒ ํŠน์ง•์„ ์ž๋™์œผ๋กœ ์ถ”์ถœํ•˜๋Š” ๋”ฅ๋Ÿฌ๋‹์˜ ์žฅ์ ์„ ํ™œ์šฉ, ์•„๋ฌด๋Ÿฐ ์ฒ˜๋ฆฌ๋„ ํ•˜์ง€ ์•Š์€ ์›๋ž˜ ๊ทธ๋Œ€๋กœ์˜ ์ƒ์ฒด ์‹ ํ˜ธ์—์„œ ์‹ ํ˜ธ ์ž์ฒด์˜ ๊ณ ์œ ํ•œ ํŠน์ง•์„ ๋ฐ˜์˜ํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค.1 Introduction 1 2 Background 5 2.1 Cuff-based BP measurement methods 9 2.1.1 Auscultatory method 9 2.1.2 Oscillometric method 10 2.1.3 Tonometric method 11 2.2 Biomedical signals used in cuffless BP prediction methods 13 2.2.1 Electrocardiography (ECG) 13 2.2.2 Photoplethysmography (PPG) 20 2.3 Cuffless BP measurement methods 21 2.3.1 PWV based BP prediction methods 25 2.3.2 Machine learning based pulse wave analysis methods 26 2.4 Deep learning for sequential biomedical data 30 2.4.1 Convolutional neural networks 31 2.4.2 Recurrent neural networks 32 3 End-to-end blood pressure prediction via fully convolutional networks 33 3.1 Introduction 35 3.2 Method 38 3.2.1 Data preparation 38 3.2.2 CNN based prediction model 41 3.2.3 Detailed architecture 45 3.3 Experimental results 47 3.3.1 Setup 47 3.3.2 Model evaluation & selection 48 3.3.3 Calibration-based method 51 3.3.4 Performance comparison 52 3.3.5 Verification using international standards for BP measurement grading criteria 54 3.3.6 Performance comparison by the input signal combinations 56 3.3.7 An ablation study of each architectural component of extraction-concentration blocks 58 3.3.8 Preprocessing of input signal to improve blood pressure prediction performance 59 3.4 Discussion 61 3.5 Summary 63 4 Blood pressure prediction by a smartphone sensor using fully convolutional networks 64 4.1 Introduction 66 4.2 Method 69 4.2.1 Data acquisition 71 4.2.2 Preprocessing of the PPG signals 71 4.2.3 PPG signal selection 71 4.2.4 Data preparation for CNN model training 72 4.2.5 Network architectures 72 4.3 Experimental results 75 4.3.1 Implementation details 75 4.3.2 Effect of PPG combination on BP prediction 75 4.3.3 Performance comparison with other related works 76 4.3.4 Verification using international standards for BP measurement grading criteria 77 4.3.5 Preprocessing of input signal to improve blood pressure prediction performance 79 4.4 Discussion 81 4.5 Summary 83 5 Improving accuracy of blood pressure prediction by distilling the knowledge of neural networks 84 5.1 Introduction 85 5.2 Methods 87 5.3 Experimental results 88 5.4 Discussion & Summary 89 6 Conclusion 90 6.1 Future work 92 Bibliography 93 Abstract (In Korean) 106Docto

    A Comparison of Deep Learning Techniques for Arterial Blood Pressure Prediction

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    Continuous vital signal monitoring is becoming more relevant in preventing diseases that afflict a large part of the worldโ€™s population; for this reason, healthcare equipment should be easy to wear and simple to use. Non-intrusive and non-invasive detection methods are a basic requirement for wearable medical devices, especially when these are used in sports applications or by the elderly for self-monitoring. Arterial blood pressure (ABP) is an essential physiological parameter for health monitoring. Most blood pressure measurement devices determine the systolic and diastolic arterial blood pressure through the inflation and the deflation of a cuff. This technique is uncomfortable for the user and may result in anxiety, and consequently affect the blood pressure and its measurement. The purpose of this paper is the continuous measurement of the ABP through a cuffless, non-intrusive approach. The approach of this paper is based on deep learning techniques where several neural networks are used to infer ABP, starting from photoplethysmogram (PPG) and electrocardiogram (ECG) signals. The ABP was predicted first by utilizing only PPG and then by using both PPG and ECG. Convolutional neural networks (ResNet and WaveNet) and recurrent neural networks (LSTM) were compared and analyzed for the regression task. Results show that the use of the ECG has resulted in improved performance for every proposed configuration. The best performing configuration was obtained with a ResNet followed by three LSTM layers: this led to a mean absolute error (MAE) of 4.118ย mmHg on and 2.228ย mmHg on systolic and diastolic blood pressures, respectively. The results comply with the American National Standards of the Association for the Advancement of Medical Instrumentation. ECG, PPG, and ABP measurements were extracted from the MIMIC database, which contains clinical signal data reflecting real measurements. The results were validated on a custom dataset created at Neuronica Lab, Politecnico di Torino

    Continuous blood pressure estimation using exclusively photopletysmography by LSTM-based signal-to-signal translation

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    Monitoring continuous BP signal is an important issue, because blood pressure (BP) varies over days, minutes, or even seconds for short-term cases. Most of photoplethysmography (PPG)-based BP estimation methods are susceptible to noise and only provides systolic blood pressure (SBP) and diastolic blood pressure (DBP) prediction. Here, instead of estimating a discrete value, we focus on different perspectives to estimate the whole waveform of BP. We propose a novel deep learning model to learn how to perform signal-to-signal translation from PPG to arterial blood pressure (ABP). Furthermore, using a raw PPG signal only as the input, the output of the proposed model is a continuous ABP signal. Based on the translated ABP signal, we extract the SBP and DBP values accordingly to ease the comparative evaluation. Our prediction results achieve average absolute error under 5 mmHg, with 70% confidence for SBP and 95% confidence for DBP without complex feature engineering. These results fulfill the standard from Association for the Advancement of Medical Instrumentation (AAMI) and the British Hypertension Society (BHS) with grade A. From the results, we believe that our model is applicable and potentially boosts the accuracy of an effective signal-to-signal continuous blood pressure estimation

    Novel Machine Learning and Wearable Sensor Based Solutions for Smart Healthcare Monitoring

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    The advent of IoT has enabled the design of connected and integrated smart health monitoring systems. These health monitoring systems can be utilized for monitoring the mental and physical wellbeing of a person. Stress, anxiety, and hypertension are the major elements responsible for the plethora of physical and mental illnesses. In this context, the older population demands special attention because of the several age-related complications that exacerbate the effects of stress, anxiety, and hypertension. Monitoring stress, anxiety, and blood pressure regularly can prevent long-term damage by initiating necessary intervention or clinical treatment beforehand. This will improve the quality of life and reduce the burden on caregivers and the cost of healthcare. Therefore, this thesis explores novel technological solutions for real-time monitoring of stress, anxiety, and blood pressure using unobtrusive wearable sensors and machine learning techniques. The first contribution of this thesis is the experimental data collection of 50 healthy older adults, based on which, the works on stress detection and anxiety detection have been developed. The data collection procedure lasted for more than a year. We have collected physiological signals, salivary cortisol, and self-reported questionnaire feedback during the study. Salivary cortisol is an established clinical biomarker for physiological stress. Hence, a stress detection model that is trained to distinguish between the stressed and not-stressed states as indicated by the increase in cortisol level has the potential to facilitate clinical level diagnosis of stress from the comfort of their own home. The second contribution of the thesis is the development of a stress detection model based on fingertip sensors. We have extracted features from Electrodermal Activity (EDA) and Blood Volume Pulse (BVP) signals obtained from fingertip EDA and Photoplethysmogram (PPG) sensors to train machine learning algorithms for distinguishing between stressed and not-stressed states. We have evaluated the performance of four traditional machine learning algorithms and one deep-learning-based Long Short-Term Memory (LSTM) classifier. Results and analysis showed that the proposed LSTM classifier performed equally well as the traditional machine learning models. The third contribution of the thesis is to evaluate an integrated system of wrist-worn sensors for stress detection. We have evaluated four signal streams, EDA, BVP, Inter-Beat Interval (IBI), and Skin Temperature (ST) signals from EDA, PPG, and ST sensors. A random forest classifier was used for distinguishing between the stressed and not-stressed states. Results and analysis showed that incorporating features from different signals was able to reduce the misclassification rate of the classifier. Further, we have also prototyped the integration of the proposed wristband-based stress detection system in a consumer end device with voice capabilities. The fourth contribution of the thesis is the design of an anxiety detection model that uses features from a single wearable sensor and a context feature to improve the performance of the classification model. Using a context feature instead of integrating other physiological features for improving the performance of the model can reduce the complexity and cost of the anxiety detection model. In our proposed work, we have used a simple experimental context feature to highlight the importance of context in the accurate detection of anxious states. Our results and analysis have shown that with the addition of the context-based feature, the classifier was able to reduce misclassification by increasing the confidence of the decision. The final and the fifth contribution of the thesis is the validation of a proposed computational framework for the blood pressure estimation model. The proposed framework uses features from the PPG signal to estimate the systolic and diastolic blood pressure values using advanced regression techniques

    ๋Œ€๊ทœ๋ชจ ์ธ๊ตฌ ๋ชจ๋ธ๊ณผ ๋‹จ์ผ ๊ฐ€์Šด ์ฐฉ์šฉํ˜• ์žฅ์น˜๋ฅผ ํ™œ์šฉํ•œ ๋น„์นจ์Šต์  ์—ฐ์† ๋™๋งฅ ํ˜ˆ์•• ๋ชจ๋‹ˆํ„ฐ๋ง ์‹œ์Šคํ…œ

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ) -- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ๊ณต๊ณผ๋Œ€ํ•™ ํ˜‘๋™๊ณผ์ • ๋ฐ”์ด์˜ค์—”์ง€๋‹ˆ์–ด๋ง์ „๊ณต, 2021. 2. ๊น€ํฌ์ฐฌ.์ตœ๊ทผ ์ˆ˜์‹ญ ๋…„ ๋™์•ˆ ๋น„์นจ์Šต์  ์—ฐ์† ํ˜ˆ์•• ๋ชจ๋‹ˆํ„ฐ๋ง์— ๋Œ€ํ•œ ํ•„์š”์„ฑ์ด ์ ์ฐจ ๋Œ€๋‘๋˜๋ฉด์„œ ๋งฅํŒŒ ์ „๋‹ฌ ์‹œ๊ฐ„, ๋งฅํŒŒ ๋„๋‹ฌ ์‹œ๊ฐ„, ๋˜๋Š” ๊ด‘์šฉ์ ๋งฅํŒŒ์˜ ํŒŒํ˜•์œผ๋กœ๋ถ€ํ„ฐ ์ถ”์ถœ๋œ ๋‹ค์–‘ํ•œ ํŠน์ง•๋“ค์„ ์ด์šฉํ•œ ํ˜ˆ์•• ์ถ”์ • ์—ฐ๊ตฌ๋“ค์ด ์ „์„ธ๊ณ„์ ์œผ๋กœ ํ™œ๋ฐœํ•˜๊ฒŒ ์ง„ํ–‰๋˜์—ˆ๋‹ค. ํ•˜์ง€๋งŒ ๋Œ€๋ถ€๋ถ„์˜ ์—ฐ๊ตฌ๋“ค์€ ๊ตญ์ œ ํ˜ˆ์•• ํ‘œ์ค€์„ ๋งŒ์กฑ์‹œํ‚ค์ง€ ๋ชปํ•˜๋Š” ๋งค์šฐ ์ ์€ ์ˆ˜์˜ ํ”ผํ—˜์ž๋“ค ๋งŒ์„ ๋Œ€์ƒ์œผ๋กœ ์ฃผ๋กœ ํ˜ˆ์•• ์ถ”์ • ๋ชจ๋ธ์„ ๊ฐœ๋ฐœ ๋ฐ ๊ฒ€์ฆํ•˜์˜€๊ธฐ ๋•Œ๋ฌธ์— ์„ฑ๋Šฅ์˜ ์ •ํ™•๋„๊ฐ€ ์ ์ ˆํ•˜๊ฒŒ ๊ฒ€์ฆ๋˜์ง€ ๋ชปํ–ˆ๋‹ค๋Š” ํ•œ๊ณ„์ ์ด ์žˆ์—ˆ๊ณ , ๋˜ํ•œ ํ˜ˆ์•• ์ถ”์ • ํŒŒ๋ผ๋ฏธํ„ฐ ์ถ”์ถœ์„ ์œ„ํ•œ ์ƒ์ฒด ์‹ ํ˜ธ๋“ค์„ ์ธก์ •ํ•˜๊ธฐ ์œ„ํ•ด ๋Œ€๋ถ€๋ถ„ ๋‘ ๊ฐœ ์ด์ƒ์˜ ๋ชจ๋“ˆ์„ ํ•„์š”๋กœ ํ•˜๋ฉด์„œ ์‹ค์šฉ์„ฑ ์ธก๋ฉด์—์„œ ํ•œ๊ณ„์ ์ด ์žˆ์—ˆ๋‹ค. ์ฒซ ๋ฒˆ์งธ ์—ฐ๊ตฌ๋Š” ๋Œ€๊ทœ๋ชจ ์ƒ์ฒด์‹ ํ˜ธ ๋ฐ์ดํ„ฐ๋ฒ ์ด์Šค๋“ค์„ ๋ถ„์„ํ•จ์œผ๋กœ์จ ์ž„์ƒ์ ์œผ๋กœ ํ—ˆ์šฉ ๊ฐ€๋Šฅํ•œ ์ˆ˜์ค€์˜ ์ •ํ™•๋„๊ฐ€ ์ ์ ˆํžˆ ๊ฒ€์ฆ๋œ ํ˜ˆ์•• ์ถ”์ • ๋ชจ๋ธ์„ ๊ฐœ๋ฐœํ•˜๋Š” ๊ฒƒ์„ ๋ชฉ์ ์œผ๋กœ ์ง„ํ–‰๋˜์—ˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” 1376๋ช…์˜ ์ˆ˜์ˆ  ์ค‘ ํ™˜์ž๋“ค์˜ ์•ฝ 250๋งŒ ์‹ฌ๋ฐ• ์ฃผ๊ธฐ์— ๋Œ€ํ•ด ์ธก์ •๋œ ๋‘ ๊ฐ€์ง€ ๋น„์นจ์Šต์  ์ƒ์ฒด์‹ ํ˜ธ์ธ ์‹ฌ์ „๋„์™€ ๊ด‘์šฉ์ ๋งฅํŒŒ๋ฅผ ํ™œ์šฉํ•œ ํ˜ˆ์•• ์ถ”์ • ๋ฐฉ์‹๋“ค์„ ๋ถ„์„ํ•˜์˜€๋‹ค. ๋งฅํŒŒ ๋„๋‹ฌ ์‹œ๊ฐ„, ์‹ฌ๋ฐ•์ˆ˜, ๊ทธ๋ฆฌ๊ณ  ๋‹ค์–‘ํ•œ ๊ด‘์šฉ์ ๋งฅํŒŒ ํŒŒํ˜• ํ”ผ์ฒ˜๋“ค์„ ํฌํ•จํ•˜๋Š” ์ด 42 ์ข…๋ฅ˜์˜ ํŒŒ๋ผ๋ฏธํ„ฐ๋“ค์„ ๋Œ€์ƒ์œผ๋กœ ํ”ผ์ฒ˜ ์„ ํƒ ๊ธฐ๋ฒ•๋“ค์„ ์ ์šฉํ•œ ๊ฒฐ๊ณผ, 28๊ฐœ์˜ ํ”ผ์ฒ˜๋“ค์ด ํ˜ˆ์•• ์ถ”์ • ํŒŒ๋ผ๋ฏธํ„ฐ๋กœ ๊ฒฐ์ •๋˜์—ˆ๊ณ , ํŠนํžˆ ๋‘ ๊ฐ€์ง€ ๊ด‘์šฉ์ ๋งฅํŒŒ ํ”ผ์ฒ˜๋“ค์ด ๊ธฐ์กด์— ํ˜ˆ์•• ์ถ”์ • ํŒŒ๋ผ๋ฏธํ„ฐ๋กœ ๊ฐ€์žฅ ์ฃผ์š”ํ•˜๊ฒŒ ํ™œ์šฉ๋˜์—ˆ๋˜ ๋งฅํŒŒ ๋„๋‹ฌ ์‹œ๊ฐ„๋ณด๋‹ค ์šฐ์›”ํ•œ ํŒŒ๋ผ๋ฏธํ„ฐ๋“ค๋กœ ๋ถ„์„๋˜์—ˆ๋‹ค. ์„ ์ •๋œ ํŒŒ๋ผ๋ฏธํ„ฐ๋“ค์„ ํ™œ์šฉํ•˜์—ฌ ํ˜ˆ์••์˜ ๋‚ฎ์€ ์ฃผํŒŒ์ˆ˜ ์„ฑ๋ถ„์„ ์ธ๊ณต์‹ ๊ฒฝ๋ง์œผ๋กœ ๋ชจ๋ธ๋งํ•˜๊ณ , ๋†’์€ ์ฃผํŒŒ์ˆ˜ ์„ฑ๋ถ„์„ ์ˆœํ™˜์‹ ๊ฒฝ๋ง์œผ๋กœ ๋ชจ๋ธ๋ง ํ•œ ๊ฒฐ๊ณผ, ์ˆ˜์ถ•๊ธฐ ํ˜ˆ์•• ์—๋Ÿฌ์œจ 0.05 ยฑ 6.92 mmHg์™€ ์ด์™„๊ธฐ ํ˜ˆ์•• ์—๋Ÿฌ์œจ -0.05 ยฑ 3.99 mmHg ์ •๋„์˜ ๋†’์€ ์ •ํ™•๋„๋ฅผ ๋‹ฌ์„ฑํ•˜์˜€๋‹ค. ๋˜ ๋‹ค๋ฅธ ์ƒ์ฒด์‹ ํ˜ธ ๋ฐ์ดํ„ฐ๋ฒ ์ด์Šค์—์„œ ์ถ”์ถœํ•œ 334๋ช…์˜ ์ค‘ํ™˜์ž๋“ค์„ ๋Œ€์ƒ์œผ๋กœ ๋ชจ๋ธ์„ ์™ธ๋ถ€ ๊ฒ€์ฆํ–ˆ์„ ๋•Œ ์œ ์‚ฌํ•œ ๊ฒฐ๊ณผ๋ฅผ ํš๋“ํ•˜๋ฉด์„œ ์„ธ ๊ฐ€์ง€ ๋Œ€ํ‘œ์  ํ˜ˆ์•• ์ธก์ • ์žฅ๋น„ ๊ธฐ์ค€๋“ค์„ ๋ชจ๋‘ ๋งŒ์กฑ์‹œ์ผฐ๋‹ค. ํ•ด๋‹น ๊ฒฐ๊ณผ๋ฅผ ํ†ตํ•ด ์ œ์•ˆ๋œ ํ˜ˆ์•• ์ถ”์ • ๋ชจ๋ธ์ด 1000๋ช… ์ด์ƒ์˜ ๋‹ค์–‘ํ•œ ํ”ผํ—˜์ž๋“ค์„ ๋Œ€์ƒ์œผ๋กœ ์ ์šฉ ๊ฐ€๋Šฅํ•จ์„ ํ™•์ธํ•˜์˜€๋‹ค. ๋‘ ๋ฒˆ์งธ ์—ฐ๊ตฌ๋Š” ์ผ์ƒ ์ƒํ™œ ์ค‘ ์žฅ๊ธฐ๊ฐ„ ๋ชจ๋‹ˆํ„ฐ๋ง์ด ๊ฐ€๋Šฅํ•œ ๋‹จ์ผ ์ฐฉ์šฉํ˜• ํ˜ˆ์•• ๋ชจ๋‹ˆํ„ฐ๋ง ์‹œ์Šคํ…œ์„ ๊ฐœ๋ฐœํ•˜๋Š” ๊ฒƒ์„ ๋ชฉ์ ์œผ๋กœ ์ง„ํ–‰๋˜์—ˆ๋‹ค. ๋Œ€๋ถ€๋ถ„์˜ ๊ธฐ์กด ํ˜ˆ์•• ์ถ”์ • ์—ฐ๊ตฌ๋“ค์€ ํ˜ˆ์•• ์ถ”์ • ํŒŒ๋ผ๋ฏธํ„ฐ ์ถ”์ถœ์„ ์œ„ํ•ด ํ•„์š”ํ•œ ์ƒ์ฒด์‹ ํ˜ธ๋“ค์„ ์ธก์ •ํ•˜๊ธฐ ์œ„ํ•ด ๋‘ ๊ตฐ๋ฐ ์ด์ƒ์˜ ์‹ ์ฒด ์ง€์ ์— ๋‘ ๊ฐœ ์ด์ƒ์˜ ๋ชจ๋“ˆ์„ ๋ถ€์ฐฉํ•˜๋Š” ๋“ฑ ์‹ค์šฉ์„ฑ ์ธก๋ฉด์—์„œ ํ•œ๊ณ„๋ฅผ ๋‚˜ํƒ€๋ƒˆ๋‹ค. ์ด๋ฅผ ํ•ด๊ฒฐํ•˜๊ธฐ ์œ„ํ•ด ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์‹ฌ์ „๋„์™€ ๊ด‘์šฉ์ ๋งฅํŒŒ๋ฅผ ๋™์‹œ์— ์—ฐ์†์ ์œผ๋กœ ์ธก์ •ํ•˜๋Š” ๋‹จ์ผ ๊ฐ€์Šด ์ฐฉ์šฉํ˜• ๋””๋ฐ”์ด์Šค๋ฅผ ๊ฐœ๋ฐœํ•˜์˜€๊ณ , ๊ฐœ๋ฐœ๋œ ๋””๋ฐ”์ด์Šค๋ฅผ ๋Œ€์ƒ์œผ๋กœ ์ด 25๋ช…์˜ ๊ฑด๊ฐ•ํ•œ ํ”ผํ—˜์ž๋“ค๋กœ๋ถ€ํ„ฐ ๋ฐ์ดํ„ฐ๋ฅผ ํš๋“ํ•˜์˜€๋‹ค. ์†๊ฐ€๋ฝ์—์„œ ์ธก์ •๋œ ๊ด‘์šฉ์ ๋งฅํŒŒ์™€ ๊ฐ€์Šด์—์„œ ์ธก์ •๋œ ๊ด‘์šฉ์ ๋งฅํŒŒ ๊ฐ„ ํŒŒํ˜•์˜ ํŠน์„ฑ์— ์œ ์˜๋ฏธํ•œ ์ฐจ์ด๊ฐ€ ์žˆ๊ธฐ ๋•Œ๋ฌธ์— ๊ฐ€์Šด์—์„œ ์ธก์ •๋œ ๊ด‘์šฉ์ ๋งฅํŒŒ์—์„œ ์ถ”์ถœ๋œ ํ”ผ์ฒ˜๋“ค์„ ๋Œ€์‘๋˜๋Š” ์†๊ฐ€๋ฝ์—์„œ ์ธก์ •๋œ ๊ด‘์šฉ์ ๋งฅํŒŒ ํ”ผ์ฒ˜๋“ค๋กœ ํŠน์„ฑ์„ ๋ณ€ํ™˜ํ•˜๋Š” ์ „๋‹ฌ ํ•จ์ˆ˜ ๋ชจ๋ธ์„ ๊ฐœ๋ฐœํ•˜์˜€๋‹ค. 25๋ช…์œผ๋กœ๋ถ€ํ„ฐ ํš๋“ํ•œ ๋ฐ์ดํ„ฐ์— ์ „๋‹ฌ ํ•จ์ˆ˜ ๋ชจ๋ธ์„ ์ ์šฉ์‹œํ‚จ ํ›„ ํ˜ˆ์•• ์ถ”์ • ๋ชจ๋ธ์„ ๊ฒ€์ฆํ•œ ๊ฒฐ๊ณผ, ์ˆ˜์ถ•๊ธฐ ํ˜ˆ์•• ์—๋Ÿฌ์œจ 0.54 ยฑ 7.47 mmHg์™€ ์ด์™„๊ธฐ ํ˜ˆ์•• ์—๋Ÿฌ์œจ 0.29 ยฑ 4.33 mmHg๋กœ ๋‚˜ํƒ€๋‚˜๋ฉด์„œ ์„ธ ๊ฐ€์ง€ ํ˜ˆ์•• ์ธก์ • ์žฅ๋น„ ๊ธฐ์ค€๋“ค์„ ๋ชจ๋‘ ๋งŒ์กฑ์‹œ์ผฐ๋‹ค. ๊ฒฐ๋ก ์ ์œผ๋กœ ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์ž„์ƒ์ ์œผ๋กœ ํ—ˆ์šฉ ๊ฐ€๋Šฅํ•œ ์ˆ˜์ค€์˜ ์ •ํ™•๋„๋กœ ์žฅ๊ธฐ๊ฐ„ ์ผ์ƒ ์ƒํ™œ์ด ๊ฐ€๋Šฅํ•œ ๋น„์นจ์Šต์  ์—ฐ์† ๋™๋งฅ ํ˜ˆ์•• ๋ชจ๋‹ˆํ„ฐ๋ง ์‹œ์Šคํ…œ์„ ๊ฐœ๋ฐœํ•˜๊ณ  ๋‹ค์ˆ˜์˜ ๋ฐ์ดํ„ฐ์…‹์„ ๋Œ€์ƒ์œผ๋กœ ๊ฒ€์ฆํ•จ์œผ๋กœ์จ ๊ณ ํ˜ˆ์•• ์กฐ๊ธฐ ์ง„๋‹จ ๋ฐ ์˜ˆ๋ฐฉ์„ ์œ„ํ•œ ๋ชจ๋ฐ”์ผ ํ—ฌ์Šค์ผ€์–ด ์„œ๋น„์Šค์˜ ๊ฐ€๋Šฅ์„ฑ์„ ํ™•์ธํ•˜์˜€๋‹ค.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 ยฑ 6.92 mmHg for systolic blood pressure (SBP), and -0.05 ยฑ 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 ยฑ 7.47 mmHg for SBP, and 0.29 ยฑ 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

    Spectrogram Analysis of Blood Pressure on Neonates with Hypoxic Ischemic Encephalopathy (HIE)

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    This paper explores the correlation between blood pressure fluctuations and the severity of Hypoxic Ischemic Encephalopathy (HIE). Via isolating particular frequency bands of blood pressure signal and calculating their power, the researcher was able to discern patients with different HIE severity and verified the assumption that less fluctuation in blood pressure is correlated with more severe brain injury. Furthermore, the researcher attempted to construct a prediction algorithm based on power within certain frequency bands of the blood pressure signal

    Increased beat-to-beat blood pressure variability is associated with impaired cognitive function

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    ACKNOWLEDGEMENTS We are grateful to Prof Dr Chin Ai Vyrn and Prof Dr Shahrul Bahyah Kamaruzzaman from Faculty of Medicine, University of Malaya for their help in MELoR study. Ageing and Age Associated Disorders Research Group for helping with patient recruitment and data collection. SOURCE OF FUNDING The Malaysian Elders Longitudinal Research (MELoR) study is now part of the Transforming Cognitive Frailty into Later Life Self-Sufficiency (AGELESS) longitudinal cohort study, currently funded by the Ministry of Higher Education Long Term Research Grant Scheme (LRGS/1/2019/UM/01/1).Peer reviewedPostprin

    Advanced Signal Processing in Wearable Sensors for Health Monitoring

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    Smart, wearables devices on a miniature scale are becoming increasingly widely available, typically in the form of smart watches and other connected devices. Consequently, devices to assist in measurements such as electroencephalography (EEG), electrocardiogram (ECG), electromyography (EMG), blood pressure (BP), photoplethysmography (PPG), heart rhythm, respiration rate, apnoea, and motion detection are becoming more available, and play a significant role in healthcare monitoring. The industry is placing great emphasis on making these devices and technologies available on smart devices such as phones and watches. Such measurements are clinically and scientifically useful for real-time monitoring, long-term care, and diagnosis and therapeutic techniques. However, a pertaining issue is that recorded data are usually noisy, contain many artefacts, and are affected by external factors such as movements and physical conditions. In order to obtain accurate and meaningful indicators, the signal has to be processed and conditioned such that the measurements are accurate and free from noise and disturbances. In this context, many researchers have utilized recent technological advances in wearable sensors and signal processing to develop smart and accurate wearable devices for clinical applications. The processing and analysis of physiological signals is a key issue for these smart wearable devices. Consequently, ongoing work in this field of study includes research on filtration, quality checking, signal transformation and decomposition, feature extraction and, most recently, machine learning-based methods

    Cuffless Blood Pressure Estimation

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    The blood pressure is an important factor in the diagnosis and evaluation of several diseases, such as acute myocardial infarction and stroke. This way, continuous monitorization of this parameter is crucial to a correct health evaluation. The current methods, like the oscillometric method, have some major drawbacks, that can influence the output values or even make the measurements impossible. One example is the high frequency evaluation of the blood pressure, in the standard used methods the process of measuring can take up to 3 minutes, and a waiting time is necessary between consecutive measurements. This dissertation presents two different cuffless solution to solve those problems. One based on physical models of the human body, and the other using machine learning techniques. In the first solution seven models that correlate pulse transit time and blood pressure, deducted by different authors, were tested to evaluate which one performed better. The testes were performed in a custom dataset acquired at Fraunhofer AICOS and in clinical environment, with two different devices (low cost device and medical grade device). The results indicate that pulse transit time can be used to track blood pressure, the developed device/method was evaluated as grade A based in the Standard IEEE 1708-2014. The second solution itโ€™s a proof of concept using a public database and three different machine learning methods (Random Forest, Neural Network and AdaBoost). Two sets of features are calculated from the ECG and PPG signals, one using TSFEL (spectral, frequency and time domain features) and a total of 15 custom features. The proposed method outperforms the methods presented in bibliography with mean absolute error of 3.6 mmHg and 2.0 mmHg to systolic and diastolic blood pressure respectively
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