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研究生: 巫俊毅
Wu, Chun-I
論文名稱: 利用雙腦半球間相關係數監測急性腦缺血之血流震盪的不對稱性
Using Inter-Hemispheric Correlation Coefficient to Monitor Asymmetric Hemodynamic Oscillation in Acute Cerebral Ischemia
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: 2019
畢業學年度: 107
語文別: 英文
論文頁數: 30
中文關鍵詞: 腦血流動力學半球間相關係數缺血性中風大腦中腦動脈閉塞近紅外光譜學
外文關鍵詞: cerebral hemodynamics, interhemispheric correlation coefficient, ischemic stroke, middle cerebral artery occlusion, near infrared spectroscopy
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  • 近紅外光譜儀(NIRS)是一種使用電磁波譜(波長范圍為700-900nm)的非侵入性腦成像技術,通過確定組織的光學特性來測量血紅蛋白濃度和氧飽和度。已經許多研究顯示了近紅外光譜儀用於監測腦血管疾病(例如中風)中的腦血流動力學的臨床潛力。 然而,研究中測量的不一致性被認為部分地歸因於解剖學差異和疾病呈現的多樣性,限制了NIRS用於中風監測的臨床可行性。在本研究中,我們首先應用頸總動脈結紮,以觀察快速的血液動力學變化。其次,對具有兩種類型的梗塞嚴重性的大腦中腦動脈閉塞(MCAO)大鼠(Koizumi’s方法)利用近紅外光譜儀進行了生物雙腦半球頻域測量。為了估計由大腦中腦動脈閉塞手術誘導的腦梗塞的程度,用2,3,5-三苯基四唑氯化物(TTC)(1.08380.0010,Merck Millipore)染色腦的冠狀切片用於組織學分析。與輕度梗死相比,嚴重梗塞的半球在急性閉塞期間表現出較低的血氧飽和度,而灌注早期的雙腦半球間相關係數(IHCC)較低,並且灌注後期的散射係數(μs')較低。雙腦半球間相關係數是區域微灌注的生物標誌物,用於驗證由動態腦自動調節中斷引起的異常半球微血管血流動力學,這可以提供梗塞面積相關的強有力證據。急性閉塞期間血紅蛋白濃度和血液飽和度的變化。有趣的是,在早期再灌注階段出現的血流動力學振蕩的半球間同步性差異與三天后發生的梗塞面積有關。最後,更強的組織散射可能反映了腦水腫的程度。
    基於大腦中腦動脈閉塞動物模型和雙腦半球間相關係數觀察,最終目標是將這些技術應用於中風患者的臨床試驗。這些近紅外光譜儀參數可能有可能成為未來轉化研究中長期卒中風監測的早期預後生物標誌物。

    Near-infrared spectroscopy (NIRS) is a non-invasive brain imaging technique using electromagnetic spectrum (wavelength ranges from 700-900nm) that measures hemoglobin concentration and oxygen saturation by determining the optical properties of tissue. Clinical potential of NIRS for monitoring cerebral hemodynamics in cerebrovascular diseases, such as stroke, has been studied. However, inconsistencies in measurements among studies, which are believed to be partly due to anatomical variance and diversity in disease presentation, limit the clinical feasibility of NIRS for stroke monitoring. In the present study, we first apply common carotid artery ligation to see the rapid hemodynamic changes. Secondly, frequency-domain NIRS measurements on hemispheres of middle cerebral artery occlusion (MCAO) rats (Koizumi’s method) with two types of infarction severity were performed. To estimate the extent of brain infarction induced by the MCAO surgery, coronal sections of the brain were stained with 2,3,5-triphenyltetrazolium chloride (TTC) (1.08380.0010, Merck Millipore) for histological analysis. Compared to minor infarction, the severely infarcted hemispheres showed lower blood oxygenation during acute occlusion, a lower interhemispheric correlation coefficient (IHCC) during the early stage of reperfusion, and a higher reduced scattering coefficient (μs’) in the late stage of reperfusion. The inter-hemispheric correlation coefficient (IHCC), a biomarker of regional micro-perfusion, is used for validating abnormal hemispheric micro-vascular hemodynamics resulting from disruption in dynamic cerebral auto-regulation, which could provide a strong evidence of infarct-size-related changes in hemoglobin concentration and blood saturation during acute occlusion. Interestingly, the discrepancy in interhemispheric synchronicity in hemodynamic oscillation appeared during the early reperfusion stage is related to the size of infarct developed three days later. Finally, the stronger tissue scattering might reflect the degree of brain edema. The ultimate goal is to apply these NIRS techniques and parameters as early prognostic biomarkers for long-term stroke monitoring in the future translational investigation.

    摘要 I ABSTRACT II 致謝 IV CONTENTS V LIST OF FIGURES VI LIST OF ABBREVIATIONS VIII CHAPTER I INTRODUCTION 1 Stroke 1 Inter-Hemispheric Correlation Coefficient 2 Near-infrared diffuse correlation spectroscopy 2 Types of NIRS 4 The aims of this study 5 CHAPTER II MATERIALS AND METHODS 7 Animal preparation 7 NIRS measurement 7 Inter-Hemispheric Correlation Coefficient Measurement 8 Common Carotid Artery Ligation (CCAL) 8 Middle Cerebral Artery Occlusion (MCAO) 12 Histological examination – TTC stain 15 CHAPTER III RESULTS 17 TTC Staining 17 Common Carotid Artery Ligation Experiment 18 Middle Cerebral Artery Occlusion 20 IHCC for MCAO model 23 CHAPTER IV DISCUSSION AND CONCLUSION 24 Non-invasive NIRS measurement 24 CCAL model 24 Quantitative NIRS measurements. in MCAO model 24 μa and μs’and in MCAO model 25 Conclusion and future work 26 REFERENCES 28

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