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研究生: 黃麗娟
Li-Chuan Huang
論文名稱: 血管自動調節之血氧程度相關功能性磁振造影
Vascular autoregulation: a BOLD fMRI study
指導教授: 許靖涵
Ching-Han Hsu
葉子成
Tzu-Chi Yeh
口試委員:
學位類別: 碩士
Master
系所名稱: 原子科學院 - 生醫工程與環境科學系
Department of Biomedical Engineering and Environmental Sciences
論文出版年: 2004
畢業學年度: 92
語文別: 中文
論文頁數: 119
中文關鍵詞: 功能性磁振影像BOLD血管自動調節腦血管反應圖
外文關鍵詞: BOLD, fMRI, vascular autoregulation, hypercapnia, cerebral vascular reactivity maps
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  • 非侵襲性的血氧程度相關功能性磁振造影(BOLD fMRI) 已是目前用在研究大腦活動相當普遍且可靠的一種方法。主要是藉由神經活動和血液動力學之間的連結間接地觀察神經活動。藉由吸入不同濃度(1-5%)的二氧化碳混合氣體為刺激方法,調控影響BOLD效應的生理機制血液動力學中的腦血流(cerebral blood flow, CBF) 因子;以blip-EPI脈衝波序在3T MR磁振造影儀取像,即時量測動態二氧化碳改變所造成BOLD訊號的變化,得到相關統計參數腦血管反應圖(cerebral vascular reactivity maps)及校正曲線。藉由觀察得到的訊號差異、統計相關反應圖做為受試者施行BOLD fMRI反應的預測、和血管自動調節功能及血管殘存的評估依據。結果顯示受試者的平均BOLD訊號改變為1.36±1.73% (平均±SD, 1%CO2) 至 7.78±3.68% (平均±SD, 5%CO2),且女性的反應比男性來得顯著。在1-5%的二氧化碳濃度範圍和BOLD訊號變化間呈現劑量依存(dose-dependent)且可觀察到BOLD訊號會隨CO2濃度改變重覆地被調控。由腦血管反應圖觀察到反應區域的分佈是一整體的效應;而對於執行握拳的運動工作時,吸入5%的二氧化碳比呼吸空氣平均有1.45±1.43% (平均±SD)的BOLD百分比增強及8-9倍顯著的空間體素增加效應。本研究在探討二氧化碳和BOLD訊號間之動態連結及血管自動調節之視覺化,並可進一步應用於腦血管疾病或生理病變時的fMRI研究。


    The principal objective of the present study was to investigate the autoregulation mechanism of cerebral vascular and predication of BOLD fMRI response with BOLD vascular reactivity maps and calibration curve. By assuming no significant increase in CMRO2 during mild hypercapnia, we measure cerebral global hemodynamic changes induced by inhalation of graded CO2 (1-5%) gas mixture by utilizing blood oxygenation level dependent (BOLD) fMRI technique. In 3T MRI system, we used the global hypercapnia stimulation to modulate hemodynamic factors and estimated the change of cerebral vascular reactivity (CVR) by BOLD signal of human brain. In 11 healthy volunteers, T2* weighted gradient echo blip-EPI was applied for the mixed trial paradigm of alternating periods of inhalation graded CO2 for 1 min after air breathing for 2 min. The averaged BOLD signal changes of subjects are 1.36 ± 1.73% (mean±SD, 1%CO2) to 7.78 ± 3.68% (mean±SD, 5% CO2), with gender difference of female dominance in CO2 response. Lesion studies of brain tumor and post-operation showed the lack of autoregulation response, as demonstrated by graded CO2 study and CVR mapping. Inhalation of 5%CO2 during performing hand-clenching motor task, as compared to control with air breathing during motor task, can enhance the BOLD signal by 1.45± 1.43%(mean±SD) and spatial extension by a factor of 8-9. Established methodology of this work enhances investigation and visualization of dynamic coupling between CO2 and BOLD signal changes, which plays the key role in fMRI studies and pathophysiology of cerebral vascular diseases.

    目次 誌謝.......................................................i 摘要......................................................ii Abstract.................................................iii 目次......................................................iv 圖表索引................................................viii 第一章 緒論.............................................1 第1-1節 前言............................................1 第1-2節 研究背景........................................2 第1-3節 文獻回顧........................................5 第1-4節 研究動機與目的.................................10 第1-5節 研究方法與流程.................................13 第1-5-1節 研究方法.....................................13 第1-5-2節 研究流程.....................................14 第1-5-2-1節 BOLD訊號的測試.............................14 第1-5-2-2節 生理監視器(Maglife C)的測試與校正..........14 第1-5-2-3節 氣體傳輸管的傳輸及延遲時間的測試...........15 第1-5-2-4節 最佳基線的測試實驗(假體及受試者)...........15 第1-5-2-5節 五種濃度二氧化碳混合氣體混合任務(mixed trial) 的BOLD訊號量測.............................16 第1-5-2-6節 呼吸5%的二氧化碳加上握拳運動及呼吸空氣加上握 拳運動.................................... 16 第1-5-2-7節 臨床病患實際應用...........................16 第二章 理論基礎........................................18 第2-1節 功能性的磁振影像(f MRI.........................18 第2-1-1節 EPI成像技術..................................19 第2-2節 腦部的活動.....................................23 第2-2-1節 腦部活動時的生理改變.........................23 第2-2-2節 血氧程度相關對比.............................25 第2-3節 磁化率對比及血氧程度相關功能圖.................29 第2-3-1節 磁化率 (magnetic susceptibility).............29 第2-3-2節 血氧程度相關的磁化率效應.....................32 第2-3-3節 內源性的磁化率對比...........................33 第2-3-4節 T2* - decay和磁化率效應......................34 第2-3-5節 fMRI訊號的改變...............................35 第2-3-6節 功能性磁振影像實驗...........................36 第2-3-7節 以BOLD訊號改變得到反應腦部活動圖.............36 第2-4節 呼吸的調節機制(regulation mechanism of respiratory)...................................38 第2-4-1節 呼吸的控制及調節中樞.........................38 第2-4-2節 化學控制中心.................................39 第2-4-3節 其他影響換氣因子.............................40 第2-4-4節 二氧化碳含量增加對吸呼的效應.................41 第2-4-5節 呼吸的自動管制功能...........................42 第2-4-6節 Pco2對呼吸的調控.............................42 第2-4-7節 血中Pco2、H+、温度和DPG濃度在血紅素飽和的機 制...........................................45 第2-5節 二氧化碳和腦部循環.............................45 第2-5-1節 二氧化碳和腦血流.............................46 第2-5-2節 二氧化碳和腦血管的調節.......................47 第2-5-3節 腦血流的調節機制.............................48 第2-5-4節 血管反應的自動調節...........................49 第2-5-5節 高碳酸症的標準化.............................50 第2-6節 大腦運動皮質區.................................51 第三章 實驗設計、材料與方法............................53 第3-1節 實驗設計.......................................53 第3-1-1節 實驗範例設計.................................53 第3-1-1-1節 假體實驗範例設計...........................54 第3-1-1-2節 人體實驗範例設計...........................54 第3-1-2節 氣體流量的設定及氣體切換.....................57 第3-2節 實驗材料.......................................58 第3-2-1節 假體.........................................58 第3-2-2節 受試者.......................................59 第3-2-3節 硬體儀器設備.................................59 第3-2-3-1節 磁振造影儀.................................59 第3-2-3-2節 附件.......................................59 第3-3節 實驗方法.......................................60 第3-3-1節 受試者受檢前的準備及定位.....................60 第3-3-2節 影像資料的取得參數...........................62 第3-3-2-1節 功能性影像取得參數.........................62 第3-3-2-2節 解剖影像的取得參數.........................63 第四章 資料分析........................................64 第4-1節 分析軟體工具...................................64 第4-2節 影像資料的前處理...............................64 第4-3節 資料的統計參數分析.............................67 第4-3-1節 理想函數的建立...............................67 第4-3-2節 空間標準化(Normalization)....................69 第4-4節 交叉相關統計(Cross correlation coefficient statistics)....................................72 第4-5節 線性模型(Linear model)的線性廻歸分析...........73 第五章 結果與討論......................................75 第5-1節 最佳基線選擇實驗...............................75 第5-2節 調控不同二氧化碳濃度混合氣體的混合區段實驗.....78 第5-3節 右手握拳運動加上5%二氧化碳濃度實驗.............88 第5-4節 再現性及臨床病患實驗...........................96 第5-5節 討論..........................................102 第六章 結論與未來方向.................................110 附錄.....................................................113 參考文獻.................................................116

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