臺灣博碩士論文加值系統

擴散張量磁振造影(diffusion tensor imaging, DTI)，為一種非侵入式的磁振造影技術，目前已經被廣泛應用在神經生理學、神經解剖學及多發性硬化症等的診斷和研究。腦中白質神經纖維束(white matter tract)的部分不等向性指標(Fractional Anisotropy, FA)明顯高於灰質，所以擴散張量影像對白質的敏感度較高；且非等向性會隨著疾病的影響和神經發育而有所改變。本研究之目的為瞭解兔腦動物模式的擴散量化指標隨著發育成長的變化及腦部神經纖維之發育情形，擬建立擴散張量磁振造影之兔腦動物模式，藉由縱向觀察紐西蘭大白兔全腦白質神經纖維之部分不等向性指標、平均擴散性(Mean Diffusivity, MD)及神經纖維走向(MR Tractography)評估比較不同發育期之變化情形。本研究以動物模式擴散張量磁振造影針對各時間點紐西蘭大白兔腦部之平均擴散性、非等向性指標及神經纖維走向進行縱向評估，結果顯示隨著紐西蘭大白兔之年齡週數增加，腦部各部位之平均擴散性值皆呈現下降趨勢。反之，腦部各部位之部分不等向性FA值皆呈現上升趨勢。DTI神經纖維走向影像之評估結果則顯示隨著紐西蘭大白兔之年齡週數增加神經纖維越來越密集且逐漸趨於完整，藉此可觀察神經纖維之發育過程，希望此研究成果可進一步應用於臨床的診斷上。

Diffusion tensor imaging (DTI), a novel non-invasive method of magnetic resonance imaging (MRI), has been wildly used in neurophysiology, neurons anatomy and multiple sclerosis diagnosis and research. Brain white matter tracts’ fractional anisotropy (FA) was significantly higher than gray matter, and sensitive to white matter in diffusion tensor imaging as well. Diffusion anisotropy changes with diseases and also with neural developments. Therefore, diffusion tensor imaging was used to acquire image data and to investigate changes in regional diffusion quantitative indices, mean diffusivity (MD), FA, and white matter fiber tract during rabbit brain developments. The results were evaluated and compared longitudinally. DTI is able to fully document integrity of neural fiber tracks and presents tissue’s microstructure in rabbit brain in vivo. The goal of this study was to study changes in regional diffusion quantitative indices and white matter fiber tract of animal brain development model. In order to present neural fiber tractography and diffusion characteristics in different regions of rabbit’s brain, time course MD, FA and MR tractography of normal New Zealand rabbits were statistically quantified longitudinally. The results showed that the MD values in each part of the New Zealand rabbits’ brain gradually decreased as they became older. On the contrary, the FA values in each part of the brain showed significantly increased as the New Zealand rabbit getting older. DTI tractography also showed that the brain neural fibers became denser and gradually showing integrity as the New Zealand rabbits getting older. Hence, it might be capable of investigating the developmental process of brain neural fiber longitudinally. It is hoped that the achievements of this study can be further applied in clinical diagnosis.

致謝 Ⅰ
中文摘要 Ⅱ
Abstract Ⅳ
表目錄 Ⅷ
圖目錄 Ⅸ
第一章緒論 1
1-1研究背景及文獻回顧 1
1-2 研究動機及目的 5
1-3 論文架構 6
第二章 原理與應用 7
2-1 MR EPI成像原理 7
2-2 MR DTI成像原理 11
2-3擴散量化指標 18
2-3-1部分不等向性（FA） 18
2-3-2平均擴散率(MD) 19
2-4神經纖維走向DTI Tractography 20
2-5兔腦解剖 22
第三章 實驗方法與步驟 29
3-1實驗方法 29
3-2實驗步驟 31
3-2-1動物準備 31
3-2-2磁振造影掃描 33
3-3影像數據處理 36
3-4統計分析 47
第四章實驗結果 48
4-1擴散張量磁振造影數據分析 48
4-2擴散張量磁振造影數據統計分析 56
4-3神經纖維走向(Tractography) 65
第五章 實驗結果 68
5-1討論 68
5-2結論 71
第六章參考文獻 72

表目錄
表2-1 兔子與人類的年齡對照表 25
表2-2 兔腦nNOS陽性神經元的密度、胞體直徑、第一級突觸數及最長突觸長度 28
表3-1 MRI掃描波序及參數 34
表4-1 紐西蘭大白兔全腦及腦部分葉區MD值之線性迴歸分析 59
表4-2 紐西蘭大白兔全腦及腦部分葉區FA值之線性迴歸分析 59
表4-3 紐西蘭大白兔全腦不同成長期MD值之線性迴歸分析 60
表4-4 紐西蘭大白兔枕葉區FA值之時變曲線 61
表4-5 紐西蘭大白兔全腦及各腦部分葉區間MD值之獨立樣本t檢定分析 62
表4-6 紐西蘭大白兔全腦及各腦部分葉區間FA值之獨立樣本t檢定分析 62
表4-7 紐西蘭大白兔全腦及各腦部分葉區間不同成長期MD值之單因子變異數多重分析 63
表4-8 紐西蘭大白兔全腦及各腦部分葉區間不同成長期FA值之單因子變異數多重分析 64

圖目錄
圖1-1 磁振擴散張量造影每年在Pubmed中收集之出版論文估計數 4
圖2-1 傳統MRI掃描波序 k-space之填入方式 7
圖2-2 EPI掃描波序k-space之填入方式 8
圖2-3 SE-EPI波序圖 9
圖2-4 擴散橢圓球體與三個特徵向量及特徵值 15
圖2-5 FA色碼圖像(color-coded FA map) 16
圖2-6 向量追蹤 21
圖2-7 兔腦冠狀面解剖構造 22
圖2-8 兔腦矢狀面解剖構造 23
圖2-9 人類腦部發育程序示意圖 25
圖2-10 兔腦之組織切片及CT影像 26
圖3-1 Siemens MAGNETOM Skyra 3.0T全身磁振造影掃描儀 30
圖3-2 15通道高解析度膝線圈 30
圖3-3 紐西蘭大白兔 31
圖3-4 Zoletil 50麻醉劑 32
圖3-5 Rompun麻醉劑 32
圖3-6 紐西蘭大白兔擺位及固定 33
圖3-7 Siemens影像處理工作站syngo影像分析軟體之操作介面 35
圖3-8 上：紐西蘭大白兔腦部解剖圖，下：與上圖對應之T2加權影像 40
圖3-9 紐西蘭大白兔各切面擴散張量影像中EPI影像 38
圖3-10 紐西蘭大白兔各切面擴散張量影像中ADC影像之ROI圈選 40
圖3-11 紐西蘭大白兔各切面擴散張量影像中FA影像之ROI圈選 42
圖3-12 紐西蘭大白兔頭部之MRI 3D T2 SPACE連續切面解剖影像 44
圖3-13 影像處理分析流程圖 46
圖4-1 紐西蘭大白兔全腦及腦部枕葉、頂葉顳葉及額葉區MD值之時變曲線 50
圖4-2 紐西蘭大白兔全腦及腦部枕葉、頂葉顳葉及額葉區
圖4-3 紐西蘭大白兔枕葉區MD值之時變曲線 51
圖4-4 紐西蘭大白兔枕葉FA值之時變曲線 51
圖4-5 紐西蘭大白兔頂葉及顳葉MD值之時變曲線 54
圖4-6 紐西蘭大白兔頂葉及顳葉FA值之時變曲線 52
圖4-7 紐西蘭大白兔額葉區MD值之時變曲線 52
圖4-8 紐西蘭大白兔額葉區FA值之時變曲線 52
圖4-9 紐西蘭大白兔全腦MD值之時變曲線 54
圖4-10 紐西蘭大白兔全腦FA值之時變曲線 54
圖4-11 紐西蘭大白兔全腦不同成長期MD值之時變曲線 55
圖4-12 紐西蘭大白兔全腦不同成長期FA值之時變曲線 55
圖4-13 第5週齡紐西蘭大白兔腦部神經纖維走向圖 65
圖4-14 第11週齡紐西蘭大白兔腦部神經纖維走向圖 66
圖4-15 第17週齡紐西蘭大白兔腦部神經纖維走向圖 66
圖4-16 第24週齡紐西蘭大白兔腦部神經纖維走向圖 67
圖4-17 紐西蘭大白兔腦組織海馬迴之神經纖維走向圖 67
 

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