在聚焦型超音波影響下，微氣泡所產生之穩態或慣性穴蝕效應可用來開啟血腦屏障，由於慣性穴蝕效應會造成出血，穩態穴蝕效應被視為較好的方式來開啟血腦屏障。為了降低非聚焦型超音波影響區域之傷害，視覺化聚焦點來得到精準的聚焦位置是非常重要的議題。本研究的目的是透過磁共振影像自迴訊脈衝序列即時觀察與定位聚焦超音波對微氣泡所產生的穩態穴蝕效應。
穩態穴蝕效應會造成局部的液體擾動，液體擾動會造成被激發的磁矩流進或流出取像平面進而導致磁共振影像訊號下降，同時，液體擾動也會導致磁矩相位分散進而造成訊號下降。我們將藉由五種不同條件設計的仿體實驗(超音波聲壓、超音波脈衝條件、磁共振影像取像平面厚度、微氣泡濃度、仿體擺放型態)以及活體實驗來觀察及探討訊號變化。
在五種條件中，微氣泡溶液均顯現顯著差異於生理食鹽水。在先前的研究中已指出超音波聲壓、超音波脈衝條件對穩態穴蝕效應的影響，在此研究中也發現相符的實驗結果。高強度的聲壓與較長的超音波脈衝長度會較強的訊號變化。此外，實驗結果發現磁共振影像平面厚度會高度影響訊號變化的程度，當取像平面厚度小於管徑時，取像平面厚度越薄所觀察到的訊號變化程度會越明顯。微氣泡的濃度則不會明顯影響訊號變化的程度。在活體實驗的部分，可以觀察到聚焦位置附近之腦組織有顯著的訊號下降，此訊號下降區域也可被本篇研究之影像處理方法所定位，且此定位區域與釓螯合物在磁共振影像上外漏區域及伊文斯藍在腦組織切片的染色區域皆高度相似。總而言之，本篇研究展示了使用磁共振影像即時觀察影像訊號改變的可行性，血腦屏障開啟的區域也可被本篇研究之影像處理方法定位。

Focused ultrasound (FUS) can locally cavitated gas-filled microbubbles (MBs) of stable cavitation (SC) and inertial cavitation (IC) to induce blood–brain barrier (BBB) opening. Because of the hemolysis caused by IC, SC is a more preferable effect to conduct to BBB opening. To reduce the damage of nontargeting brain tissue, imaging guidance is crucial to localize transient BBB opening. The aim of this study is to real-time localize and monitor SC-induced BBB-opening by a half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence.
SC would cause locally turbulent flow around focal point. Turbulent flow can make excited spins flow out of imaging plane and induce intravoxel dephasing effect, resulting in signal drop in MR image. In vitro experiments in static or flowing phantom and in vivo experiment were conducted in this study to observe the signal change. We designed in vitro experiment with five conditions including acoustic pressure, duty cycle and pulse repetition frequency (PRF), slice thickness, MB concentration, and posture of phantom.
We found that in vitro experiments of different experimental conditions all shown the significant difference of SI changes between microbubble and normal saline solutions. Increasing acoustic pressure would result in greater radial expansion ratio of MBs, resulting in more significant SI changes. Longer duty cycle as well as lower PRF allowed longer pulse length to accumulate the energy from FUS pulse, also increasing SI changes. Ratio of MR slice thickness to chamber/vessel diameter highly influenced the degree of signal change. As for in vivo experiment, SI changes around focal point in tissue could be observed and localized by cavitation index (CI) map, which was highly consistent with Gd leakage and EB dye. In conclusion, this study demonstrates the feasibility of real-time monitoring SC-induced SI changes, and the location of BBB opening could be identified through the computation of SC-induced SI changes.

ABSTRACT
CONTENTS
Chapter 1 Introduction………………………………………………………1
1.1 Focused ultrasound and microbubbles 1
1.1.1 Mechanisms of microbubbles combined with focused ultrasound 1
1.1.2 BBB opening 2
1.2 Monitoring of FUS cavitation 4
1.2.1 Ultrasound 4
1.2.2 Optical observation 4
1.2.3 MRI 4
1.3 Motivation 5
1.4 Dissertation Orientation 5
Chapter 2 Theory………………………………………………………………………6
2.1 HASTE sequence 6
2.2 Theory of SI change 6
2.2.1 Turbulent flow effect on MR acquisition 6
2.2.2 FUS applied on different k-lines 10
Chapter 3 Methods and Results: in vitro…………14
3.1 Methods: 3T MRI 14
3.1.1 MBs preparation 14
3.1.2 Phantom preparation 15
3.1.3 Experimental set-up 15
3.1.4 Ultrasound parameter 16
3.1.5 MRI acquisition 16
3.1.6 Data analysis process 18
3.2 Methods: 7T MRI 19
3.2.1 Phantom preparation 19
3.2.2 Experimental set-up 19
3.2.3 Ultrasound parameter 20
3.2.4 MRI acquisition 20
3.2.5 Data analysis process 22
3.3 Results: 3T MRI 23
3.3.1 Acoustic pressure 23
3.3.2 Duty cycle and PRF 25
3.3.3 Ratio of MR slice thickness to chamber diameter 29
3.3.4 MBs concentration 31
3.3.5 Posture of phantom 33
3.4 Results: 7T MRI 35
3.4.1 Static phantom 35
3.4.2 Flowing phantom: Acoustic pressure 37
3.4.3 Flowing phantom: Ratio of MR slice thickness to chamber diameter 40
Chapter 4 Methods and Results: in vivo…………42
4.1 Methods 42
4.1.1 Animal preparation 42
4.1.2 Experimental set-up 43
4.1.3 Ultrasound sonication 45
4.1.4 MRI acquisition 45
4.1.5 Data analysis process 47
4.1.6 Histology 50
4.2 General Results 51
4.3 Results: Control Rat 54
4.4 Results: Experimental Rat 58
Chapter 5 Discussion and Conclusion…………………67
5.1 In vitro: 3T and 7T 67
5.1.1 Acoustic pressure 67
5.1.2 Duty cycle and PRF 67
5.1.3 Ratio of MR slice thickness to chamber diameter 68
5.1.4 MBs concentration 69
5.1.5 Posture of phantom 70
5.2 In vivo: 7T 71
5.2.1 SI changes 72
5.2.2 Mappings 72
5.3 Limitations 74
5.4 Conclusions 75
5.5 Future Work 76
Chapter 6 References…………………………………………………………77
Chapter 7 Supplementary Materials………………………82
Appendix I……………………………………………………………………………………86
Appendix II…………………………………………………………………………………91

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