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研究生: 賴方儀
Lay, Fang-Yi
論文名稱: 使用高頻超音波彈性成像技術偵測不同年齡之小鼠腦部彈性性質於體外研究
High Resolution Ultrasound Elastography for Mice Brain in Aging Research: In vitro Study
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: 70
中文關鍵詞: 超音波系統瞬時彈性成像剪切波速腦部老化
外文關鍵詞: Ultrasound, Transient elastography, Shear wave velocity, Aging brain
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  • 隨著醫療產業的蓬勃發展與老年人口的比例逐年增加,許多由衰老導致的疾病開始受到社會關注。其中,腦部神經退化所產生的疾病最為大家所擔憂。疾病如:阿茲海默症和帕金森氏症等,皆與腦部老化導致的記憶力退化、認知功能和運動功能喪失有關。然而,腦部退化疾病目前還沒有根治的方法,因此如何早期的診斷與預防是研究人員所關心的議題。目前已有許多文獻指出藉由量測組織的黏彈性質可以作為診斷腦部變異的指標之一,雖然臨床上大多使用核磁共振技術量測彈性影像,但在小動物的研究中,其計算出的彈性影像仍不足以分辨不同腦區的彈性性質。
    為了進一步了解彈性性質在不同年齡層與各個腦區的關聯性,此研究提出一個使用超音波原理的二維高頻瞬時彈性成像技術來估計小鼠腦部的剪切模量。在系統架構中,主要會使用到一個外部震盪器作為低頻(100-500 Hz)組織震動的來源,以及一個31.25 MHz高頻超音波換能器與超快速超音波成像系統來追蹤剪切波動的傳遞情況。此實驗中會配製兩種模擬組織的仿體用來驗證實驗架構和演算法的可行性,而其結果也表明此方法是具有可靠性且可以計算出高解析度(<300 μm)的彈性影像。
    在小鼠的動物實驗中,由於海馬迴與大腦皮質是最容易受到腦部老化影響的區域,因此實驗主要關注於這兩區域的彈性變化。實驗量測的老鼠將分為4個月與11個月大的兩個年齡組別,用來觀察老化與腦部彈性的差異。實驗結果發現不論年齡的差異,海馬迴皆會比大腦腦皮質來得軟化,但在不同腦區的比較上,海馬迴軟化的程度會比大腦皮質更容易受到年齡老化的影響。此研究結果可以作為腦部早期診斷的資訊,以利於腦部變異的發現及治療。

    The brain disorders such as Parkinson's disease (PD) and Alzheimer disease (AD) with memory loss usually happen in aging people. Due to the increment of aging population, the neurodegeneration followed by aging brain has been regarded as an important issue. In recently, viscoelastic properties are used as a diagnostic marker for brain stiffness identification and disorder progression tracking. The mainstream of diagnostic equipment in brain tissue is magnetic resonance elastography (MRE), however, the resolution of elastogram is not good enough to distinguish between different regions in the small animal brain. To obtain more elastic information between aging and brain properties, this study proposed to use high frequency 2D transient elastography based on ultrasound technique for estimating the shear modulus of the mouse brain in vitro study. The system structure includes an external vibrator with low excitation frequency (100-500 Hz) for tissue motion generation and a 31.25 MHz high frequency linear array transducer with ultrafast ultrasonic system for tracking shear wave propagation. The experiments also used two kinds of the phantom to validate the algorithm and experimental methods. The validation results show this estimation method is reliable and provides the high resolution (<300 μm) elastic image. In the small animal experiments, the region of interest is focused on the hippocampus and cortex of brain tissue. Two different ages of mice group (4, 11 months) were prepared to research the brain elastic variation. The results show the elasticity of hippocampus is softer than cortex in all groups. But compared with different regions, the hippocampus elasticity has more significant decrease with age than the cortex. These results give a clinically relevant information to discover the irregular brain tissue for previous treatment of brain’s disease.

    Contents 摘要 III Abstract IV 誌謝 V Contents VI Tables IX Figures X Chapter 1 Introduction 1 1.1 Background 1 1.2 Literature Reviews 3 1.3 Motivations and Purpose 8 Chapter 2 Basic Theory 9 2.1 Ultrasound 9 2.1.1 Fundamental of Acoustic Propagation 9 2.1.2 Stress and Strain Relationships 10 2.1.3 Compressional Wave and Shear Wave 11 2.1.4 Reflection, Refraction and Attenuation 13 2.2 Ultrasonic Imaging 15 2.2.1 A-Mode Imaging 16 2.2.2 B-Mode Imaging 16 2.2.3 M-Mode Imaging 17 2.3 Elasticity 18 2.3.1 Elastic Modulus 18 2.4 Shear Wave Elasticity 21 2.4.1 Shearwave Dispersion Ultrasound Vibrometry (SDUV) 21 2.4.2 Transient Elastography (TE) 23 Chapter 3 Materials and Methods 25 3.1 System Overview 25 3.1.1 Experimental System Structure 25 3.1.2 Ultrasound Imaging System 26 3.1.3 System Setup 27 3.2 Data Processing 29 3.2.1 IQ Data Acquisition and Displacement Calculation 29 3.2.2 Displacement Filtering 30 3.2.3 Shear Wave Research in Region of Interest (ROI) 30 3.2.4 Time of Flight and Wave Velocity Calculation 32 3.2.5 Regional Segmentation in Velocity Map 32 3.2.6 Group Elasticity Calculation 33 3.2.7 Resolution Calculation 34 3.3 Phantom Preparation 35 3.3.1 Polyvinyl Alcohol (PVA) Phantom 35 3.3.2 Gelatin Phantom 38 3.4 Compression Testing System 40 3.5 Density Assessments 41 3.6 Animal Model Preparation 43 Chapter 4 Results 45 4.1 Phantom Validation Results 45 4.1.1 PVA Phantom 45 4.1.2 Gelatin Phantom 48 4.2 Animal Experiment Results 50 Chapter 5 Discussions 54 5.1 Vibration Source Type 54 5.2 System Setup 55 5.3 Phantom Experiment 56 5.4 Animal Experiment 58 5.5 Limitations 60 Chapter 6 Conclusions 61 Chapter 7 Future Works 62 References 63

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