乳癌的前期治癒率極高，隨著癌細胞開始轉移，其治癒率大幅下降，使得監測乳癌轉移與否對於控制病情至關重要，而關鍵要角即是癌細胞轉移首站：前哨淋巴結；臨床上使用前哨淋巴結切片手術判斷癌症是否發生轉移，然而此侵入式手術會產生一定的後遺症，使得細針抽吸切片的低侵入特性受到重視，但其需要搭配影像系統輔助導引。
我們先前提出的超快磁致動超音波與其使用的超順磁性奈米粒子能夠在超音波影像上辨別出前哨淋巴結的能力，然而單一脈衝形式之外加磁場，其激發之磁致動位移量同為單一脈衝形式，不僅雷同於生物體中的組織位移形式，其振幅亦小於一個波長，使磁致動位移遭生物體中的組織位移所掩蓋。本研究為了突破單一脈衝法在活體上的應用瓶頸，採取了循環式脈衝以差異化磁致動位移與組織位移，並進一步驗證其於小動物活體研究之可靠度。
活體研究使用三種磁奈米粒子之注射濃度，2.1毫克鐵、1.05毫克鐵，以及最低濃度為 0.21毫克鐵。最低濃度略低於臨床劑量 0.23毫克。各濃度皆測試三組以上以強化可靠度，結果皆成功分辨前哨淋巴結。離體實驗被進一步用以證實其結果之正確性。在以上各組研究中，我們皆討論了 90分鐘內磁奈米粒子的累積狀況、磁致動位移量與劑量之關係、系統穿透深度、系統辨識位移量之低限。

For the prognosis in breast cancer, the detection of metastasis at the early stage is important. The sentinel lymph node biopsy (SLNB) is the golden standard to determine metastasis. However, it is invasive. A less-invasive choice, fine needle aspiration biopsy (FNAB), would be beneficial for staging the axillary lymph nodes without surgical intervention while it needs image guidance.
Our previously proposed pulsed magneto-motive ultrasound (pMMUS) with superparamagnetic iron oxide nanoparticles (SPIOs) injection has shown the feasibility of non-invasive SLN identification. However, the sub-wavelength displacement profile corresponding to the applied single pulsed excitation can be easily overwhelmed by tissue motion. In this study, we propose cyclic magneto-motive ultrasound (cMMUS) to overcome the difficulties that pMMUS has met.
In vivo rat experiments with 2.1, 1.05 and 0.21 mg doses of SPIO have been repeated for 5, 3 and 3 times, respectively. The 0.21-mg dose in our experiment is lower than the clinical used one. The SLN identification and reliability of the proposed method have been confirmed. Ex vivo experimental results comfirmed the in vivo ones. Overall, we demonstrated the capability of the proposed cMMUS for noninvasive SLN identification in vivo, which owns a great potential in image guidance of SLN FNAB.

摘要 I
Abstract II
Table of Contents III
List of Figures VI
Chapter 1. Introduction 1
1.1 Breast cancer and sentinel lymph node (SLN) 1
1.2 Potential image guidance for needle biopsy 4
1.2.1. Ultrasound imaging 5
1.2.2. Magnetic resonance imaging (MRI) 7
1.2.3. Photoacoustic imaging 7
1.2.4. Magneto-motive ultrasound (MMUS) 8
1.2.4.1. Concept of MMUS 9
1.2.4.2. Continuous wave MMUS (CW-MMUS) 10
1.2.4.3. Pulsed MMUS (pMMUS) 11
1.3 Superparamagnetic particles as contrast agents 12
1.3.1. Characteristics of lymphatic system 12
1.3.2. Mechanism of SPIO’s targeting to SLNs 14
1.3.3. Superparamagnetism of SPIOs 14
1.3.4. Magnetic response of SPIOs 16
1.4 Displacement tracking algorithm for MMUS 17
1.4.1. Time-delay estimator 18
1.4.2. Phase-difference estimator 19
1.4.3. Cramer-Rao Lower Bound (CRLB) 22
1.5 Motivation 23
1.6 Organization of the thesis 23
Chapter 2. Materials and Methods 25
2.1 Ultrafast cyclic magneto-motive ultrasound (cMMUS) 25
2.1.1. Cyclic magnetic pulse 25
2.1.2. Ultrafast plane wave imaging 27
2.1.3. Hardware setup 29
2.1.3.1. Programmable magnetic pulser 29
2.1.3.2. Electromagnet 30
2.1.3.3. Ultrasound engine 32
2.1.3.4. cMMUS system setup 33
2.2 Signal processing 35
2.2.1. Dynamic receiving focusing 35
2.2.2. Magneto-motion tracking 36
2.2.3. Motion artifact suppressing 37
2.2.3.1. Normalized cross correlation 37
2.2.3.2. Peak detection 38
2.2.4. Practical lower bound 39
2.3 Animal handling 40
2.3.1. Imaged lymph node on rats 40
2.3.2. SPIO and methylene blue 41
2.3.3. Experimental procedure 43
Chapter 3. Results and Discussions 48
3.1 2.1-mg Fe dose of SPIO 48
3.1.1. In-vivo experiments 48
3.1.2. Ex vivo experiments 53
3.2 1.05-mg Fe dose of SPIO 55
3.2.1. In-vivo experiments 55
3.2.2. Ex-vivo experiments 58
3.3 0.21-mg Fe dose of SPIO 59
3.3.1. In-vivo experiments 59
3.3.2. Ex-vivo experiments 63
3.4 Discussions 64
3.4.1. Relation of dose, displacement profile and limitation of tracking 64
3.4.2. Accumulation time 67
3.4.3. Penetration depth 69
Chapter 4. Conclusions and Future Work 72
4.1 Conclusions 72
4.2 Future work 73
References 75

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