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研究生: 李炘哲
Li, Hsin-Che
論文名稱: 高頻超快速超音波血流成像技術應用於阿茲海默症老鼠大腦
High Frequency Ultrafast Ultrasound Blood Flow Mapping for Mice Brain with Alzheimer’s Disease
指導教授: 黃執中
Huang, Chih-Chung
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: 2018
畢業學年度: 106
語文別: 英文
論文頁數: 57
中文關鍵詞: 阿茲海默症腦血管密度高頻超音波超快速超音波成像血流成像
外文關鍵詞: Alzheimer’s disease, Cerebrovascular density, High frequency ultrasound, Ultrafast ultrasound imaging, Blood flow mapping
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  • 腦血管密度的降低是阿茲海默症發病機制中的重要指標。由於臨床前研究對於了解阿茲海默症的真正病因十分重要,因此小動物模型已經廣泛應用於阿茲海默症的研究之中。在先前的研究中,組織學分析和掃描式電子顯微鏡常用於量化腦血管,但若要得到腦血流的動態資訊,活體內的量測是必要的。本論文中提出了高頻超快速超音波血流成像技術,用於繪製活體內小鼠腦血管。因為目前還沒有關於此技術用於小鼠大腦的研究,所以在本論文中討論了此技術的表現:能偵測到最小48 μm的血管且能區分兩個血管的最小距離是73 μm。
    此外,此技術應用在年輕及老年正常小鼠和阿茲海默症小鼠的腦血管密度量測,用以比較各組之間的差異。實驗結果顯示,不同年齡的正常小鼠在腦皮質與海馬迴的腦血管密度相似,但與同齡的正常小鼠相比,阿茲海默症小鼠的腦血管密度在腦皮質與海馬迴分別降低了30%和50%。這些結果與先前的研究結果一致。
    在本論文中,對於高頻超快速超音波血流成像技術應用在小動物大腦中的表現進行討論,並且成功發展此技術以建立了在小鼠腦血管密度與阿茲海默症的相關性。

    Reduced cerebrovascular density is an important indicator in the pathogenesis of Alzheimer’s disease (AD). Preclinical study is essential to understand the true cause of AD, as a result, AD small animal models have been applied widely on AD researches. In the previous studies, histologic analysis and SEM are often used for quantifying the cerebral blood vessels, however, an in vivo method is required for the dynamic information of cerebral blood flow in the small animals. A high frequency ultrafast ultrasound blood flow mapping technique was proposed for in vivo mapping the blood vessels of the mice brain in this study. Because there is no research with this technique for the brain in mice currently, the performance of this technique was discussed: the minimal vessel of 48 μm was detected and the distance of 73 μm between two different vessels was distinguished by using this technique.
    In addition, this technique was applied on the measurement of cerebrovascular densities in vivo in young and aged wild-type (WT) mice and genetically modified AD mice to compare the difference between each group. Experimental results show that cerebrovascular densities are similar in the cortex and hippocampus for WT mice with different ages but reduced 30% in the cortex and 50% in the hippocampus for AD mice compared with age-matched WT mice. These results are consistent with the previous studies.
    In this study, an in vivo high frequency ultrafast ultrasound blood flow mapping technique was discussed its performance for the brain in the small animals and developed successfully to establish the correlation between reduced cerebrovascular density and AD in the mice.

    摘要 I Abstract II 誌謝 III Contents IV List of Tables VI List of Figures VII Chapter 1 Introduction 1 1.1 Alzheimer’s Disease (AD) 1 1.2 Brain Microvascular Imaging Modalities 3 1.3 Motivation and Specific Aims 6 Chapter 2 Theoretical Foundation 7 2.1 Ultrasound 7 2.1.1 Reflection, Refraction and Attenuation 8 2.1.2 Doppler Effect 10 2.1.3 Ultrasound Transducer 11 2.2 Ultrasound Imaging 13 2.3 Ultrafast Ultrasound Imaging 17 2.3.1 Plane Wave Transmission 18 2.3.2 Coherent Plane Wave Compounding 19 2.3.3 Ultrafast Blood Flow Imaging 24 Chapter 3 Materials and Methods 27 3.1 Animal Models 27 3.1.1 Wide-type (WT) Mice 28 3.1.2 Alzheimer’s Disease (AD) Mice 29 3.2 Experimental Setup 30 3.3 Ultrafast Ultrasound Imaging Procedure 31 3.4 Parameter Comparison 33 3.5 Cerebrovascular Density Quantification 33 3.6 Statistics 34 Chapter 4 Results 35 4.1 Parameter Comparison 35 4.2 Image Resolution 38 4.3 Directional Information 39 4.4 Evaluation from AD Mice 40 Chapter 5 Discussion 44 Chapter 6 Conclusion 47 Chapter 7 Future Work 48 References 49

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