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研究生: 邱昱植
YU-CHIH CHIU
論文名稱: 結合穿戴式脈波量測、機器學習與脈波分佈區間分析(PDA)應用於肌少症早期評估及探討
Combining wearable pulse wave measurement, machine learning, and Pulse Distribution Analysis (PDA) in early assessment and discussion of sarcopenia
指導教授: 許昕
Hsin Hsiu
口試委員: 吳立偉
Li-Wei Wu
高震宇
Chen-Yu Kao
學位類別: 碩士
Master
系所名稱: 應用科技學院 - 醫學工程研究所
Graduate Institute of Biomedical Engineering
論文出版年: 2022
畢業學年度: 110
語文別: 中文
論文頁數: 114
中文關鍵詞: 肌少症代謝症候群肌力障礙穿戴式裝置循環系統機器學習脈波分佈區間分析法PDA
外文關鍵詞: sarcopenia, metabolic syndrome, muscular disorder, wearable device, circulatory system, machine learning, pulse distribution analysis, PDA
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  • 肌少症不只影響老年人的行動能力、生活品質,同時還會增加罹病率以及死亡率。現有診斷肌少症的方式,經常伴隨著高成本、儀器低可及性以及可能有輻射曝露等問題,且通常需到醫院接受一系列檢查,因此能促進方便性、即時性且具有準確性的肌少症診斷工具便是迫切且尚未滿足的醫療需求。
    現有研究已發現循環系統疾病與肌少症之間存在關聯性。動脈血管特性變化會影響肌少症疾病的發展。本研究會藉由本實驗室自行開發的穿戴式脈波量測裝置來量測動脈脈波,藉以探討患有肌少症早期症狀族群(Possible sarcopenia,簡稱PSarco)與一般壯健民眾(Robust)於血管特性的差異,而為了達到更早期偵測肌少症的目的,亦會將肌少症的潛在因子 — 潛在代謝症候群(PreMetS)也納入與肌少症合併分析。
    有133名前來老年健康檢查的民眾接受了雙盲實驗,進行了3分鐘非侵入式的血壓波形量測。經收案統計,可得到Robust有 74人;PSarco 有59人。本研究會採用脈波頻域分析和機器學習(ML)分析(以40個頻域諧波參數為特徵:能量比例(Cn)及其變異係數(CVn),相位角(Pn)及其標準偏差(Pn_SD))來進行數據分析,並自行開發一個脈波評分系統 — 脈波分佈區間分析法 ( PDA ),來提供更輕便且快速的分析方式。
    本研究結果發現,PSarco與Robust在眾多頻域諧波參數上具有顯著差異,尤其Cn在全部10個諧波皆具有顯著性。將PreMetS也納入合併分析,可發現伴隨著兩者症狀的發生,對於血管特性會有最嚴重的影響。基於這些基礎,在ML的表現,經三倍交叉驗證(3-fold cross-validation)結果,使用LDA分類器模型分類的性能AUC可高達0.74。而使用PDA的結果AUC最終可高達0.83,兩者皆已達到可實務應用的標準。
    基於藉由觀察因肌少症引起的血管特性改變而造成動脈脈波傳輸條件變化的測量和分析,最終得到以下幾點結論:
    1. 患有肌少症症狀的病患(PSarco)與一般壯健民眾(Robust)在眾多頻域諧波上具有顯著的差異性。
    2. 與Robust相比,同時患有代謝症候群與肌少症症狀的受試者(PSarco_PreMetS)存在著最明顯的差異。
    3. 使用ML分析,經3-fold cross-validation的結果,使用 LDA 分析時分類性能AUC可高達0.74,運算相較PDA更仔細且全面,隨著樣本數持續增加預計會有更好的表現,適合雲端運算。
    4. 使用PDA分析,分類性能AUC可高達0.83,且運算簡單快速,適合裝置端運算。
    5. 目前的量測與分析(包括 ML 分析和PDA分析)檢測肌少症引起的動脈脈波傳輸條件變化,有助於提供一種非侵入式且易於使用的方法,來判別可能肌少症(PSarco),未來可望結合雲端架構,來提供使用者更全面性的服務。


    Sarcopenia not only affects the mobility and quality of life of the elderly but also increases morbidity and mortality. Existing modalities for diagnosing sarcopenia are often associated with high cost, low instrument accessibility, and possible radiation exposure, and often require a series of tests in a hospital, thus facilitating convenient, timely, and accurate diagnosis. A diagnostic tool for sarcopenia is an urgent and unmet medical need.
    Existing research has found an association between circulatory disorders and sarcopenia, with changes in arterial vascular properties affecting the development of sarcopenia. This study will use the wearable pulse wave measurement device developed in our laboratory to measure the arterial pulse wave, to explore the blood vessels of the early symptom group of possible sarcopenia (PSarco) and the general healthy people (robust). For early detection of sarcopenia, underlying metabolic syndrome (PreMetS), a potential sarcopenic factor, was also included in the combined analysis with sarcopenia.
    A 3-minute non-invasive blood pressure waveform measurement was performed on 133 people who came to the elderly health check-up in a double-blind experiment. According to the statistics, there are 74 people in Robust and 59 people in PSarco. This research will use pulse wave frequency domain analysis and machine learning (ML) analysis (characterized by 40 frequency domain harmonic parameters: energy ratio (Cn) and its coefficient of variation (CVn), phase angle (Pn), and its standard deviation (Pn_SD)) for data analysis, and developed a pulse wave scoring system—Pulse Distribution Analysis (PDA) to provide a lighter and faster analysis method.
    The results of this study found that PSarco and Robust have significant differences in many frequency-domain harmonic parameters, especially Cn is significant in all 10 harmonics. When PreMetS was included in the pooled analysis, it was found that the most severe impact on vascular properties was associated with the occurrence of both symptoms. Based on these foundations, in the performance of ML, the AUC of the classification performance using the LDA classifier model can be as high as 0.74 by 3-fold cross-validation results. The AUC of the results using PDA can be as high as 0.83, both of which have reached the standard of practical application.
    Based on the measurement and analysis of changes in arterial pulse wave transmission conditions by observing changes in vascular properties due to sarcopenia, the following conclusions were drawn:
    1. Patients with sarcopenia symptoms (PSarco) and general healthy people (Robust) have significant differences in many frequency-domain harmonics.
    2. Compared with Robust, subjects with both metabolic syndrome and sarcopenia symptoms (PSarco_PreMetS) had the most significant differences.
    3. Using ML analysis, after 3-fold cross-validation results, the classification performance AUC can be as high as 0.74 when using LDA analysis. Compared with PDA, the operation is more careful and comprehensive. As the number of samples continues to increase, it is expected to have better performance. Suitable for cloud computing.
    4. Using PDA analysis, the classification performance AUC can be as high as 0.83, and the calculation is simple and fast, which is suitable for device-side calculation.
    5. Current measurements and analyses (including ML analysis and PDA analysis) to detect changes in arterial pulse wave transmission conditions caused by sarcopenia help to provide a non-invasive and easy-to-use method to identify possible sarcopenia (PSarco), in the future, it is expected to combine the cloud architecture to provide users with more comprehensive services.

    論文摘要 i Abstract iii 目錄 v 表索引 viii 圖索引 ix 第一章. 緒論 1 1.1. 研究背景 1 1.1.1. 肌少症 1 1.1.2. 目前肌少症之診斷評估 2 1.1.3. 循環系統與肌少症之關係 3 1.1.4. 穿戴式裝置用於生理的即時觀測 4 1.2. 研究動機及目的 5 第二章. 研究設計 7 2.1. 硬體開發 8 2.2. 軟體分析方式 9  頻域參數比較 9  AI機器學習分析(ML) 9  脈波分佈區間劃分法分析(PDA) 9 2.3. 臨床收案介紹 10 2.3.1. 受試者納入及排除條件 11 2.3.2. 收案流程 11 2.3.3. 量測方式 11 2.3.4. 量測步驟 12 2.4. 實驗分組 14 2.5. 實驗規劃 15 第三章. 實驗硬體介紹 17 3.1. 心電訊號描述放大器(Electrocardiography, ECG) 18 3.2. 動脈血壓波形感測器(Blood Pressure Waveform, BPW) 20 3.3. 血管光容積感測器(Photoplethysmography, PPG) 23 3.4. 數位類比轉換器(DAQ) 26 3.5. 擷取介面程式 27 第四章. 分析方法與參數介紹 28 4.1 MATLAB程式分析流程 29 4.1.1 切波分析參數 30 4.1.2 擷取介面之BPW、PPG波形圖 31 4.2 頻域參數 31 4.3 機器學習應用與演算法介紹: 33 4.3.1 機器學習演算法 33 4.3.2 機器學習方法概述 39 4.4 脈波分佈區間分析 ( PDA ) 41 4.4.1 第一版 41 4.4.2 第二版 (改良版) 42 第五章. 實驗結果 44 5.1 針對肌少症與壯健組的頻域諧波參數差異探討 45 5.2 肌少症早期偵測實驗 51 5.2.1 可能肌少症組與壯健組頻域諧波參數差異比較 52 5.2.2 透過機器學習來做可能肌少症組與壯健組自動化資料分類 56 5.3 結合代謝症候群與肌少症早期症狀深入探討 59 5.3.1 代謝症候群對於頻域諧波參數上的影響 60 5.3.2 肌少症與代謝症候群症狀綜合比較 64 5.3.3 透過結合代謝症候群症狀重新強化機器學習分類能力 69 5.4 快速肌少症早期偵測實驗 73 5.4.1 脈波分佈區間分析(PDA) 74 5.4.2 改良脈波分佈區間分析 78 5.5 性別比例控制實驗 82 5.5.1 可能肌少症組與壯健組單純女性比較及自動化分類 82 5.5.2 可能肌少症組與壯健組單純女性比較及自動化分類 88 第六章. 結論與未來展望 94 第七章. 參考文獻 99

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