超快循環式磁致動超音波前哨淋巴結造影：活體小動物研究

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研究生：	張宇君 Chang, Yu-Chun
論文名稱：	超快循環式磁致動超音波前哨淋巴結造影：活體小動物研究 Ultrafast Cyclic Magnetomotive Ultrasound Imaging of Sentinel Lymph Nodes: In Vivo Small Animal Study
指導教授：	李夢麟 Li, Meng-Lin
口試委員:	葉秩光 Yeh, Chih-Kuang 沈哲州 Shen, Che-Chou
學位類別：	碩士 Master
系所名稱：	電機資訊學院 - 電機工程學系 Department of Electrical Engineering
論文出版年：	2017
畢業學年度：	105
語文別：	英文
論文頁數：	81
中文關鍵詞：	超快循環式磁致動超音波、前哨淋巴結、活體小動物研究、磁致動超音波
外文關鍵詞：	Ultrafast Cyclic Magnetomotive Ultrasound, In Vivo Small Animal Study, Sentinel Lymph Node, Magnetomotive Ultrasound
相關次數：	點閱：2 下載：0
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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    Breast cancer and sentinel lymph node (SLN)    1
2    Potential image guidance for needle biopsy    4
2.1.    Ultrasound imaging    5
2.2.    Magnetic resonance imaging (MRI)    7
2.3.    Photoacoustic imaging    7
2.4.    Magneto-motive ultrasound (MMUS)    8
2.4.1.    Concept of MMUS    9
2.4.2.    Continuous wave MMUS (CW-MMUS)    10
2.4.3.    Pulsed MMUS (pMMUS)    11
3    Superparamagnetic particles as contrast agents    12
3.1.    Characteristics of lymphatic system    12
3.2.    Mechanism of SPIO’s targeting to SLNs    14
3.3.    Superparamagnetism of SPIOs    14
3.4.    Magnetic response of SPIOs    16
4    Displacement tracking algorithm for MMUS    17
4.1.    Time-delay estimator    18
4.2.    Phase-difference estimator    19
4.3.    Cramer-Rao Lower Bound (CRLB)    22
5    Motivation    23
6    Organization of the thesis    23
Chapter 2.    Materials and Methods    25
1    Ultrafast cyclic magneto-motive ultrasound (cMMUS)    25
1.1.    Cyclic magnetic pulse    25
1.2.    Ultrafast plane wave imaging    27
1.3.    Hardware setup    29
1.3.1.    Programmable magnetic pulser    29
1.3.2.    Electromagnet    30
1.3.3.    Ultrasound engine    32
1.3.4.    cMMUS system setup    33
2    Signal processing    35
2.1.    Dynamic receiving focusing    35
2.2.    Magneto-motion tracking    36
2.3.    Motion artifact suppressing    37
2.3.1.    Normalized cross correlation    37
2.3.2.    Peak detection    38
2.4.    Practical lower bound    39
3    Animal handling    40
3.1.    Imaged lymph node on rats    40
3.2.    SPIO and methylene blue    41
3.3.    Experimental procedure    43
Chapter 3.    Results and Discussions    48
1    2.1-mg Fe dose of SPIO    48
1.1.    In-vivo experiments    48
1.2.    Ex vivo experiments    53
2    1.05-mg Fe dose of SPIO    55
2.1.    In-vivo experiments    55
2.2.    Ex-vivo experiments    58
3    0.21-mg Fe dose of SPIO    59
3.1.    In-vivo experiments    59
3.2.    Ex-vivo experiments    63
4    Discussions    64
4.1.    Relation of dose, displacement profile and limitation of tracking        64
4.2.    Accumulation time    67
4.3.    Penetration depth    69
Chapter 4.    Conclusions and Future Work    72
1    Conclusions    72
2    Future work    73
References    75


                                

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