以核磁共振之灌流、擴散與磁共振頻譜影像分析高脂飲食與CRMP-1基因缺乏老鼠之海馬迴

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研究生：	洪子明 Hung, Tzu-Ming
論文名稱：	以核磁共振之灌流、擴散與磁共振頻譜影像分析高脂飲食與CRMP-1基因缺乏老鼠之海馬迴 Magnetic resonance perfusion, diffusion, and spectroscopy in hippocampus of high fat diet and CRMP-1 gene deficiency mouse models
指導教授：	彭旭霞 Peng, Hsu-Hsia
口試委員:	周銘鐘 Chou, Ming-Chung 金亭佑 Chin, Ting-Yu 蔡炳煇 Tsai, Ping-Huei
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：	2022
畢業學年度：	111
語文別：	英文
論文頁數：	126
中文關鍵詞：	磁共振影像、灌流、擴散、頻譜、CRMP-1基因缺乏、高脂飲食、失智
外文關鍵詞：	Magnetic resonance imaging, Perfusion, Diffusion, Spectroscopy, CRMP-1 gene deficiency, High fat diet, Dementia
相關次數：	點閱：2 下載：0
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使用磁共振成像(magnetic resonance imaging, MRI)的研究對於了解失智症的病理機制至關重要。失智症的發生常伴隨海馬體的病變。失智症可以藉由CRMP-1基因敲除(crmp-1−/−)來先天性地造成，亦可由後天食用高脂飲食(high fat diet, HFD)來誘發。據悉，尚未有研究使用不同 MRI 技術來對先天和後天造成的失智症進行綜合的分析。因此，本研究的目的為使用核磁共振之灌流、擴散與磁共振頻譜影像來更全面地評估先天性(CRMP-1小鼠模型)與後天性(HFD小鼠模型)失智老鼠對海馬迴的影響。在對失智小鼠的海馬迴分析中，crmp-1−/−和HFD小鼠的平均擴散係數(mean diffusivity, MD)亦均增加。crmp-1−/−小鼠具有較高的非等向性指標(fractional anisotropy, FA)，而 HFD小鼠則有相反趨勢。在 crmp-1−/−小鼠中，麩醯胺酸/麩胺酸 (glutamine/glutamate, Glx)和總肌酸(total creatine, t-Cr)的比率上升，而在HFD小鼠中則發現N-乙酰天冬氨酸(N-acetyl aspartate, NAA)和 t-Cr比率呈下降趨勢。綜上所述，本研究對先天性和後天性失智小鼠的海馬迴進行灌注、擴散和磁共振頻譜參數的定量。且由分析結果可觀測到此二失智症狀小鼠模型對於海馬迴造成了不同程度的改變情形。

Research applying magnetic resonance imaging (MRI) has been essential to understand the pathological mechanisms of dementia. The occurrence of dementia is often accompanied with hippocampus abnormalities. Dementia can be congenitally caused by CRMP-1 gene knockout (crmp-1−/−) or developed by consumption of high fat diet (HFD). To the best of our knowledge, the integrated analysis of dementia between congenital and developed model utilizing different MRI techniques have not been explored. The aim of this study was to estimate the influence of congenital (crmp-1−/− mouse model) and developed (HFD mouse model) dementia on the hippocampus in a more comprehensive manner by applying MR perfusion, diffusion, and spectroscopy techniques. In the hippocampus of the dementia mouse model, mean diffusivity (MD) increased in both crmp-1−/− and HFD mice. crmp-1−/− mice possessed enhanced fractional anisotropy (FA) while HFD mice demonstrated an opposite trend. The ratio of glutamine/glutamate (Glx) between total creatine (t-Cr) increased in crmp-1−/− mice while a decreased trend of N-acetyl aspartate (NAA) and t-Cr ratio was found in HFD mice. In conclusion, this study examined the perfusion, diffusion and MRS parameters on the hippocampus of congenital and developed dementia mice and suggested the different impact to the hippocampus of the two models.

Chapter 1 Introduction-----1
1 Dementia-----1
2 Magnetic resonance imaging (MRI) techniques-----2
2.1 Perfusion MRI-----2
2.2 Diffusion MRI-----2
2.3 Magnetic resonance spectroscopy (MRS)-----4
3 Effects of CRMP-1 gene knockout (crmp-1−/−) on the hippocampus---4
4 Effects of high fat diet (HFD) consumption on the hippocampus----5
5 Motivation-----6

Chapter 2 Methods-----8
1 Animal preparation-----8
1.1 crmp-1−/− model-----8
1.2 HFD model-----8
2 Perfusion MRI-----9
2.1 MRI acquisition-----9
2.2 Preprocessing-----11
Preprocessing: SPM-----11
Preprocessing: De-spike-----12
2.3 Gamma variate fitting-----13
2.4 rCBV calculation and normalization-----16
2.5 Hippocampus ROI selection-----17
2.6 Statistical analysis-----17
3 Diffusion MRI-----18
3.1 MRI acquisition-----18
3.2 Mathematical calculation-----18
Mathematical calculation: Fitting of apparent diffusion and kurtosis coefficient-----18
Mathematical calculation: Derivation of DTI parameters-----19
Mathematical calculation: Derivation of DKI parameters-----21
3.3 Hippocampus ROI selection-----23
3.4 Statistical analysis-----28
4 MRS-----29
4.1 MRI acquisition-----29
4.2 Data analysis-----30

Chapter 3 Results: Optimization of perfusion calculation-----31
1 signal processing-----31
1.1 ΔR2* peak truncation-----31
1.2 Gamma variate fitting-----34
2 rCBV & normalization-----37
2.1 rCBV & normalization: Normalization using AIF-----37
2.2 rCBV & normalization: Normalization using other ROIs-----42

Chapter 4 Results: crmp-1−/− model-----44
1 Perfusion MRI-----44
2 Diffusion MRI-----47
3 MRS-----59

Chapter 5 Results: HFD model-----60
1 Perfusion MRI-----60
2 Diffusion MRI-----63
3 MRS-----74

Chapter 6 Discussion-----75
1 Optimization of perfusion calculation-----76
1.1 Negative ΔR2* peak-----76
1.2 rCBV normalization-----77
2 crmp-1−/− model-----78
2.1 Perfusion MRI-----78
2.2 Diffusion MRI-----78
2.3 MRS-----80
3 HFD model-----81
3.1 Perfusion MRI-----81
3.2 Diffusion MRI-----81
3.3 MRS-----82
4 Comparison of the two models-----84
5 Slice comparison of DTI parameters-----85
6 Limitations-----86
7 Conclusions-----88
8 Future work-----89

Chapter 7 Reference-----91

Chapter 8 Appendix-----98
1 Abbreviation list-----98
2 Supplementary materials-----101
2.1 Quantification of diffusion parameters of slice 3-5 altogether-----101
2.2 Intra-observer ROI selection-----106
2.3 Susceptibility of self-developed code and DKE to noise-----108
2.4 Bonferroni correction of slice comparison-----111
3 Response of oral defense-----121
4 Plagiarism detection-----126
                                

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