擴散峰度造影在臨床上已被提出為評估大腦白質與灰質的可行性工具。然而，擴散峰度造影的參數最佳化仍有待討論的部分。此外，傳統的擴散峰度造影利用其衍生的參數之平均值評估不同腦區之表現，但不同腦區之神經組織異質性卻常因此被忽略。本研究的目的包含了探討擴散峰度造影參數的重複時間(repetition time, TR)和擴散梯度方向數的最佳化，以及利用各腦區像素值的變異係數評估神經組織異質性的潛在價值。我們利用高血壓大鼠(spontaneously hypertensive rats, SHR)、高血壓大鼠對照的正常血壓大鼠(Wistar Kyoto rat, WKY)，以及一般的正常大鼠(Sprague Dawley rat, SD)來評估。結果發現，TR越長時可能會有來自麻醉造成的影響，導致擴散峰度造影衍生的參數值被觀察到產生改變，因此TR時間短至硬體設備上可接受時，或許即為建議的TR時間長度。而20個擴散梯度方向數與標準的30個方向數之計算結果差異不大，但少於15個方向數時計算結果的誤差較大，因此擴散梯度方向數被建議為至少20個方向。而由變異係數評估神經組織異質性的可行性在本研究被發現，由變異係數所得的神經組織異質性在SHR和與其對應的WKY，以及一般正常血壓大鼠(WKY與SD)間具有鑑別差異的能力，且其鑑別的能力優於傳統平均值的效果。因此由變異係數測量的神經組織異質性可能是個有潛力的非侵入式生物影像指標去探討組織異質性的方法，而在評估高血壓或神經退化性疾病進程時提供協助。

Diffusion kurtosis imaging (DKI) has been proposed to evaluate brain microstructural environment in both white and gray matter tissues. However, the optimization of DKI parameters is still in discussion. Besides, previous studies usually evaluate the tissue integrity by mean values and the tissue heterogeneity assessment is often disregarded. The aim of this study is to investigate the optimization of DKI parameters including repetition time (TR) and diffusion direction numbers, and the latent value of heterogeneity approached from DKI. Tissue heterogeneity evaluated by coefficient of variation (CV) of DKI was investigated to examine its capability of distinguishing diseased and normal groups. We evaluated the tissue heterogeneity by using spontaneously-hypertensive rats, Wistar Kyoto rats, and Sprague-Dawley rats. Results indicated the TR as short as hardware workable and direction numbers at least 20 directions were revealed. The tissue heterogeneity evaluated by CV of DKI showed the feasibility of differentiating hypertension strain and normotensive strains better than mean values. In conclusion, the current study demonstrated the tissue heterogeneity assessed by CV of DKI may have the potential to detect pathological changes and could be a helpful non-invasive biomarker to evaluate disease progression.

摘要
Abstract
Dedication
Chapter 1 Introduction-------------------------------------------1
1.1 Introduction of Diffusion Kurtosis Imaging (DKI)------------1
1.1.1 Diffusion MRI--------------------------------------------1
1.1.2 Theory of DKI--------------------------------------------3
1.1.3 DT and KT derived parameters-----------------------------7
1.2 Effects of parameters in DKI-------------------------------12
1.3 Tissue Heterogeneity in pathology--------------------------14
1.4 Motivation-------------------------------------------------16
Chapter 2 Materials and Methods---------------------------------18
2.1 Animal preparation-----------------------------------------18
2.2 MRI Acquisition--------------------------------------------18
2.3 Data Analysis----------------------------------------------20
2.3.1 DT and KT derived maps----------------------------------20
2.3.2 Reconstruction and RMSE evaluation of different numbers-20
2.3.3 Regions-of-interest-------------------------------------21
2.3.4 Tissue heterogeneity------------------------------------22
2.4 Statistical Analysis---------------------------------------22
Chapter 3 Results-----------------------------------------------24
3.1 Intra-strain variation evaluation--------------------------24
3.2 Different Repetition Time----------------------------------26
3.3 Different Diffusion Directions Numbers---------------------31
3.4 Inter-strains comparison-----------------------------------44
3.4.1 DT and KT derived indices in different strains----------44
3.4.2 Tissue heterogeneity in different strains---------------48
3.4.3 ROC curve analysis--------------------------------------51
Chapter 4 Discussion--------------------------------------------62
4.1 Comparison of parameters in DKI----------------------------62
4.1.1 Repetition time-----------------------------------------62
4.1.2 Diffusion directions numbers----------------------------64
4.2 Inter-strains differences in DKI---------------------------66
4.2.1 DT and KT derived indices-------------------------------66
4.2.2 Tissue heterogeneity------------------------------------71
4.3 Limitations------------------------------------------------74
Chapter 5 Conclusions-------------------------------------------76
5.1 Conclusions------------------------------------------------76
5.2 Future Work------------------------------------------------77
Chapter 6 References--------------------------------------------78
Appendix I------------------------------------------------------85
Appendix II-----------------------------------------------------86
Appendix III----------------------------------------------------87

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