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研究生： 陳昕緻
Chen, Hsin-Chih
論文名稱： 應用功能性近紅外光光譜儀探討肌少症患者的肌腦軸線之血流動力學
Investigating Hemodynamics of Muscle-Brain Axis in Sarcopenia Patients Using Functional Near-Infrared Spectroscopy
指導教授： 陳家進
Chen, Jia-Jin
學位類別： 碩士
Master
系所名稱： 工學院 - 生物醫學工程學系
Department of BioMedical Engineering
論文出版年： 2024
畢業學年度： 112
語文別： 英文
論文頁數： 68
中文關鍵詞： 肌少症 、功能性近紅外光譜(fNIRS) 、肌腦軸線 、肌肉因子 、腦氧合 、肌肉氧合 、血流動力學反應
外文關鍵詞： Sarcopenia, Functional near-infrared spectroscopy (fNIRS), Muscle-brain axis, Myokine, Cerebral oxygenation, Muscle oxygenation, Hemodynamic response
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    • 背景
    肌少症是一種與老化相關的症候群，其特徵是骨骼肌質量減少，伴隨肌肉力量減弱或身體機能下降兩者之一。肌少症的併發症之一是認知能力下降，這表明肌肉和大腦之間存在一種關係，稱為肌腦軸線，主要由肌肉產生的細胞因子（肌肉因子）介導。體力活動（運動）可以提高肌肉因子的血液濃度，誘導這種從骨骼肌到大腦的訊號傳導，在運動對認知的有益作用中扮演部分的角色。肌腦軸線的機制尚未完全明瞭；它不僅與肌肉因子有關，也與大腦和肌肉血流動力學的變化有關。透過生物指標（肌肉因子）分析，並應用功能性近紅外光譜儀（fNIRS），我們研究了運動期間的生理機制以及腦部和肌肉血流動力學變化，以探討肌肉收縮與大腦活動之間的關係。

    方法
    共有九位老年參與者，被分為兩組：肌少症組六名、非肌肉減少症組三名（SA組：6；非SA組：3）。他們都接受了單次重複等長膝關節伸展運動，並在運動前後進行休息狀態下的基線量測和認知測試。運動強度設定為最大自主收縮（MVC）的70%。在等長收縮和血液再灌注期間，使用fNIRS監測大腦皮質（前額葉皮質）和腿部肌肉（右側股直肌）的血流動力學變化（帶氧血紅素 HbO的濃度：[HbO]、去氧血紅素HbR的濃度：[HbR]）。計算運動過程中肌肉[HbR] 擬合曲線的參數和曲線下面積(AUC)值。此外，也收集血液樣本進行生物指標分析。研究了SA組和非SA組之間的差異。

    結果
    我們將運動區間分為兩個不同的時期：等長收縮時期和血液再灌注（恢復）時期。整體而言，在等長收縮時期，所有個體的肌肉 [HbR] 均增加。然而，肌肉 [HbO] 表現出不一致的模式：大多數顯示下降，而三位受試者顯示增加（SA組：2；非SA組：1）。在 PFC 中，所有個體的大腦 [HbO] 均增加。然而，大腦 [HbR] 顯示不一致的模式：大多數顯示下降，而兩位顯示增加（SA：1；非SA組：1）。此外，與肌少症患者相比，非肌少症參與者表現出更高的肌肉 [HbO] AUC 絕對值 (P = .0001) 、更大的肌肉 [HbR] 強度 (P = .004) 、以及血液再灌注期間中更長的拐點時間 (P = .0002)。然而，就前額葉皮質的腦血流動力學而言，兩組之間沒有統計上的顯著差異。

    結論
    使用 fNIRS 和生物指標分析，我們研究了患有和不患有肌少症的個體的肌肉和大腦血流動力學。我們的目的是從神經影像工具和生物標記的角度檢查肌腦軸線。肌少症組較低的肌肉[HbO] AUC絕對值和肌肉[HbR]強度可能表示肌少症患者腿部肌肉組織的氧提取和供氧效率較低，可能是由於肌肉血管功能較差或肌力減弱所致。肌少症組在血液再灌注期間中，有較短的拐點時間，顯示肌少症患者的血流恢復和氧氣補充機制可能受損。因此，我們的研究為患有和不患有肌少症的個體之間的血流動力學差異提供了有力的證據。fNIRS可作為一種非侵入性、低成本、便攜式方法來評估肌少症患者的肌肉和大腦血流動力學，有助於更好地了解肌腦軸線以及肌少症、肌肉、體力活動、大腦和認知功能之間的關係。

    Sarcopenia is an age-related syndrome characterized by decreased skeletal muscle mass, reduced muscle strength, and a decline in physical performance. One of the complications of sarcopenia is cognitive decline, indicating a relationship between muscle and brain, known as the muscle-brain axis, which is mediated by muscle-produced cytokines called myokines. Physical activity (PA) can elevate the myokine level, inducing this kind of signaling from skeletal muscle to the brain, which at least partially contributes to the beneficial effect of PA on cognition. The mechanism of the muscle-brain axis is not fully elucidated. It is not merely related to myokines but also the cerebral and muscle hemodynamic changes. The aim of this study is to apply functional near-infrared spectroscopy (fNIRS) for investigating the physiological mechanism and the cerebral and muscle hemodynamic changes during PA which further explores the relationship between muscle contraction and brain activity.
    A total of 9 elderly participants were divided into two groups: 6 in the sarcopenia group and 3 in the non-sarcopenia group (SA: 6; non-SA: 3). They all underwent a single session of repetitive isometric knee extension exercise with baseline recording and cognitive tests conducted before and after the exercise. The exercise intensity was set at 70% of the maximal voluntary contraction (MVC). Using fNIRS, hemodynamic changes (concentration of HbO and HbR) in the brain cortex (prefrontal cortex, PFC) and leg muscle (right rectus femoris, RF) were monitored during the isometric contraction and reperfusion periods. The parameters of the fitting curve for muscle [HbR] and the area under the curve (AUC) values during the exercise were calculated. Additionally, blood samples were collected for biomarker analysis. Differences between the SA and non-SA groups were examined.
    We divided a single exercise block into two distinct periods: isometric contraction and reperfusion (recovery) periods. Overall, during the isometric contraction period, all individuals experienced an increase in muscle [HbR]. However, muscle [HbO] exhibited an inconsistent pattern: most showed a decrease, while three showed an increase (SA: 2; non-SA: 1). In the PFC, all individuals showed an increase in brain [HbO]. However, brain [HbR] displayed an inconsistent pattern: most showed a decrease, while two showed an increase (SA: 1; non-SA: 1). Additionally, compared to sarcopenia patients, non-sarcopenia participants demonstrated higher absolute AUC values for muscle [HbO] (P = .0001), greater intensity for muscle [HbR] (P = .004), and longer inflection time during the reperfusion period (P = .0002). However, regarding cerebral hemodynamics in the PFC, there are no statistically significant differences between these two groups.
    Using fNIRS and biomarker analysis, we investigated the muscle and cerebral hemodynamics of individuals with and without sarcopenia. We aimed to examine the muscle-brain axis from a neuroimaging tool and biomarker perspective. The lower absolute muscle [HbO] AUC value and muscle [HbR] intensity may indicate that sarcopenia patients have lower efficiency of oxygen extraction and supply in leg muscle tissues, possibly due to poor muscle vascular function or weakened muscle strength. The shorter inflection time during the reperfusion period suggests that sarcopenia patients' blood flow recovery and oxygen replenishment mechanisms may be impaired. Accordingly, our study provides robust evidence of hemodynamic differences between individuals with and without sarcopenia. fNIRS may serve as a non-invasive, low-cost, and portable method to evaluate muscle and cerebral hemodynamics in sarcopenia, aiding in a better understanding of the muscle-brain axis and the relationship among sarcopenia, muscle, physical activity, brain, and cognition.

    摘要 I Abstract III 誌謝 VI Table of Contents VII List of Tables X List of Figures XI Chapter 1 Introduction 1 1.1. Sarcopenia 1 1.1.1. Diagnosis of sarcopenia 1 1.1.2. Etiology of sarcopenia 2 1.1.3. Sarcopenia, cognitive impairment, and potential mechanisms 3 1.2. Physical Activity and Role of Myokines in the Muscle-Brain Axis 4 1.2.1. The muscle-brain axis and the role of myokines 4 1.2.2. The importance and roles of myokines in brain function 4 1.2.3.  The relationship between physical activities and cognition, and the potential mechanisms 6 1.3. Functional Near-Infrared Spectroscopy (fNIRS) for Investigating Tissue Oxygenation 7 1.3.1 Principle of functional near-infrared spectroscopy (fNIRS) 8 Chapter 2 Materials and Methods 12 2.1. Participants 12 2.2. Procedures 14 2.2.1 Experimental procedures 14 2.2.2. Blood sample collection and analysis 16 2.3.  fNIRS Recordings 17 2.4.  Data Analysis 18 2.5.  Statistical Analysis 22 Chapter 3 Results 23 3.1.  Overall Muscle and Cerebral Hemodynamic Changes during Isometric Exercise 23 3.2.  Muscle [HbR] Changes during the Isometric Contraction and Reperfusion Periods 28 3.3.  Muscle [HbO] Changes during the Isometric Contraction Period 33 3.4.  Brain [HbR] Changes during the Isometric Contraction Period 35 3.5.  Brain [HbO] Changes during the Isometric Contraction Period 37 3.6.  Cognitive Test Results for Each Subject 39 Chapter 4 Discussion and Conclusion 41 4.1. Hemodynamic Response Function Difference Between Sarcopenia and Non-Sarcopenia Elderly Adults 41 4.1.1.  Hemodynamic response of muscle (RF) [HbR] 41 4.1.2.  Hemodynamic response of muscle (RF) [HbO] 42 4.1.3.  Hemodynamic response of brain (PFC) [HbR] and [HbO] 42 4.2.  Impact of Different Exercise Intensities on PFC and Muscle Activation 44 4.3.  Inconsistencies in Cerebral and Muscle [HbO] and [HbR] Responses during Isometric Exercise 45 4.3.1.  Comparison with previous studies 45 4.3.2.  Our study findings 45 4.3.3.  Gender differences in hemodynamic response function 47 4.4. Study Limitations and Future Directions 47 4.4.1.  Studies limitations 47 4.4.2.  Future directions 48 4.5. Conclusion 48 References 50

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