近年來，使用微氣泡搭配聚焦型超音波來開啟血腦屏障的研究已被廣為使用，而藉由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梯度迴訊脈衝序列即時觀察聚焦超音波對微氣泡所產生的慣性穴蝕效應，藉由七種不同條件設計的仿體實驗以及活體實驗來觀察及探討訊號變化。
慣性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上升或下降，且液體擾動會導致磁矩相位分散進而造成訊號下降。這些發現都證實使用磁共振影像梯度迴訊脈衝序列來即時觀察聚焦超音波對微氣泡所產生的慣性穴蝕效應的可行性。
七種條件分別為：微氣泡濃度、超音波聲壓、磁共振影像取像平面厚度、超音波脈衝條件、流動液體實驗、梯度流體補償。在七種條件中均顯現顯著差異於微氣泡溶液及生理食鹽水。在先前的研究中已指出微氣泡濃度、超音波聲壓、超音波脈衝條件對慣性穴蝕效應的影響，在此研究中也發現相符的實驗結果。濃度較濃的微氣泡以及高強度的聲壓會延長訊號下降的時間。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，當取向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。而流體補償梯度會導致訊號上升使訊號更容易偵測。在活體實驗的部分，無論聚焦於腦中央大靜脈或是腦組織中均可以觀察到聚焦位置有顯著的訊號下降。

Recently, gas-filled microbubble (MB) cooperated with focused ultrasound (FUS) is known as a feasible technology to open blood brain barrier. It is an important issue to visualize the focal point for detecting the accurate location of FUS pulses. The aim of this study was to use gradient echo MRI to real-time monitor focused ultrasound inertial cavitation (IC) on microbubbles. Seven kinds of in vitro experimental conditions (MB concentration, acoustic pressure, slice thickness, pulse repetition frequency (PRF) and duty cycle, intermittent FUS mode, flowing phantom, flow compensation) and in vivo experiment were tested in this study to observe the signal change.
Inertial cavitation would cause locally turbulent flow around focal point. Turbulent flow can lead to excited MR spins flow in or out of imaging slice and intravoxel dephasing effect, and therefore resulted in signal enhance or signal drop. These findings indicate the feasibility of real-time monitoring of focused ultrasound inertial cavitation on microbubbles by gradient echo MRI.
These results of seven designs all showed the significant difference between microbubble and normal saline solutions. Previous studies have showed the effects of MB concentration and FUS conditions, the corresponding results in this study also observed. Denser MB concentration and higher acoustic pressure would prolong the duration of SI drop. Moreover, ratio of MR slice thickness to chamber/vessel diameter has highly influenced on the degree of signal change. As MR slice thickness was thinner than chamber diameter, thinner MR slice thickness would cause more obvious SI changes. Flow compensation gradient would lead to signal enhance and easier to detecting. As for in vivo experiment, signal around focal point had obvious signal drop during experimental process even though FUS focused on sinus or tissue.

Chapter 1 Introduction ………………………………………………………….………1
1.1 Focused ultrasound and microbubbles 1
1.1.1 Introduction to focused ultrasound 1
1.1.2 Introduction to microbubbles 1
1.1.3 Mechanisms of microbubbles combined with focused ultrasound 2
1.1.4 Application of BBB opening 3
1.1.5 Application of MB in MRI 4
1.2 Monitoring of FUS cavitation 5
1.2.1 Ultrasound 5
1.2.2 Optical observation 5
1.2.3 MRI 6
1.3 Overview of dissertation 7
Chapter 2 Theory ……………………………………………………………………….8
2.1 FLASH sequence 8
2.2 Theory of SI change 9
2.2.1 Turbulent flow effect on MR acquisition 9
2.2.2 FUS applied on different klines 11
Chapter 3 Materials and Methods ………………………………………………...14
3.1 Microbubbles preparation 14
3.2 In vitro experiment 14
3.2.1 3T MRI 14
3.2.2 7T MRI 19
3.3 In vivo experiment 23
3.3.1 Animal preparation 23
3.3.2 Experimental set-up 23
3.3.3 Ultrasound parameter 25
3.3.4 MRI acquisition 25
3.3.5 Data analysis process 26
3.3.6 Histology 27
Chapter 4 Results ……………………………………………………………………...28
4.1 MBs concentration at 3T 28
4.2 Acoustic pressure at 3T 32
4.3 Slice thickness at 3T 39
4.4 PRF and duty cycle at 3T 43
4.5 Intermittent mode at 3T 44
4.6 Low acoustic pressure at 3T 45
4.7 Flowing phantom at 7T 46
4.8 Flow compensation at 7T 49
4.9 In vivo experiments at 7T 50
Chapter 5 Discussion ………………………………………………………………...55
5.1 MB concentration at 3T 55
5.2 Acoustic pressure at 3T 55
5.3 Slice thickness at 3T 56
5.4 PRF and duty cycle at 3T 56
5.5 Flowing phantom at 7T 57
5.6 Flow compensation at 7T 57
5.7 In vivo experiments at 7T 58
5.8 Limitations 59
Chapter 6 Conclusions ………………………………………………………………...60
6.1 Conclusions 60
6.2 Future Work 60
Chapter 7 References ………………………………………………………………...61

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