在乳癌早期診斷中，前哨淋巴結是判斷癌細胞是否擴散的關鍵；現在臨床上主要依賴前哨淋巴結切片(sentinel lymph node biopsy, SLNB)來做判斷，過程中放射性對比劑的使用與取出淋巴結的手術所帶來後遺症促使了細針抽吸切片(fine needle aspiration biopsy, FNAB)的誕生，但其需要搭配即時影像導引細針穿刺。
在各種醫學影像中，超音波成像最適合做為影像導引；但是在傳統超音波成像中僅能辨別出淋巴結的存在，無法從影像判斷是否為前哨淋巴結。我們認為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具有在超音波影像上辨別出前哨淋巴結的能力，因此在活體上測試其可行性，部分結果中能夠看到前哨淋巴結被成功分辨出來。
此外，有文獻指出在惡性腫瘤擴散時，組織細胞之機械特性會受到影響，為此我們測試了在超快磁致動超音波下估量組織彈性的可能性。但由於位移曲線會同時受到磁奈米粒子在組織中的濃度影響，且組織中的濃度目前無從得知，使得直接從最大位移量來推算組織彈性不可行。
在聲輻射力脈波影像(acoustic radiation force impulse imaging, ARFI)中，有人提出基於特定黏彈模型之推導來估算黏彈比；由於超快磁致動超音波與聲輻射力脈波影像在原理上具有一定的相似度，因此我們認為此推導能夠擴展應用在超快磁致動超音波上，並呈現初步模擬結果。

Recently, fine needle aspiration biopsy (FNAB) has emerged as a less-invasive alternative to replace the standard surgical procedure for breast cancer staging, but a needle-guided imaging which can identify the sentinel lymph node (SLN) is needed.
Ultrasound imaging is more suitable than other non-invasive imaging methods due to the cost-effective and portable properties, but a new contrast agent is needed to identify SLN. Magneto-motive ultrasound (MMUS), which leverages the superparamagnetic iron oxide nanoparticles (SPIOs) used in MRI, has potential in SLN identification. The feasibility is demonstrated in vivo using our previously proposed pulsed MMUS (pMMUS), and the SLN is enhanced from surrounding tissues.
Since the displacement time profile in pMMUS may be correlated to mechanical property which can provide information of lesions, two factors that would influence displacement curve are discussed. The maximum displacement increases with elasticity decreasing and SPIO concentration increasing; thus it is impossible to separate these two factors and estimate elasticity simply using pMMUS displacement. A method to estimate viscosity-elasticity ratio is proposed in acoustic radiation force impulse imaging (ARFI), and it is feasible to utilize the same concept in pMMUS to solve the elasticity-estimation problem mentioned above. A preliminary simulation using this concept is also presented.

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 Noninvasive imaging modalities 3
1.2.1. Ultrasound imaging 4
1.2.2. Magnetic resonance imaging (MRI) 4
1.2.3. Photoacoustic imaging 5
1.2.4. Magneto-motive ultrasound (MMUS) 6
1.3 Viscoelasticity changes in SLN 7
1.4 Motivation 8
1.5 Organization of the thesis 9
Chapter 2. Materials and Methods 11
2.1 Ultrafast pulsed magneto-motive ultrasound (pMMUS) 11
2.1.1. Time-varying magnetic fields 11
2.1.2. Ultrafast plane wave imaging 12
2.1.3. pMMUS system setup 13
2.1.4. Signal processing 15
2.2 Animal handling 17
2.2.1. Imaged lymph node on rats 17
2.2.2. SPIO and methylene blue 18
2.2.3. Experimental procedure 20
2.3 Phantom preparation 21
Chapter 3. Results and Discussions 23
3.1 SLN identification 23
3.1.1. Ex vivo experiment 23
3.1.2. In vivo experiment 26
3.1.3. Discussions 30
3.2 Phantom experiment 31
3.2.1. Displacement vs. SPIO concentration 31
3.2.2. Displacement vs. Elasticity 32
3.2.3. Discussions 33
Chapter 4. Conclusions and Future Work 35
4.1 Conclusions 35
4.2 Future work 35
Reference 38

[1] Olivia Jane Scully, Boon-Huat Bay, George Yip and Yingnan Yu, “Breast cancer metastasis,” Cancer Genomics and Proteomics September-October 2012 vol. 9 no.5 311–320.
[2] Lyman GH, Giuliano AE, Somerfield MR, et al, “American Society of Clinical Oncology: American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer,” J Clin Oncol. 2005 Oct 20, 23 (30): 7703–20.
[3] Umberto Veronesi, Giovanni Paganelli, Viviana Galimberti, et al, “Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes,” The Lancet, Volume 349, Issue 9069, 1864–1867.
[4] Giuliano AE, Kirgan DM, Guenther JM, Morton DL, “Lymphatic mapping and sentinel lymphadenectomy for breast cancer,” Ann Surg 1994, 220 (3): 391-398, discussion 398–401.
[5] Veronesi U, Paganelli G, Viale G, et al, “A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer,” N Engl J Med 349: 546–553, 2003.
[6] Morton DL, Thompson JF, Essner R, et al, “Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: A multicenter trial—Multicenter selective lymphadenectomy trial Group,” Ann Surg 230:453–465, 1999.
[7] Todd N. Erpelding, Chulhong Kim, Manojit Pramanik, et al, “Sentinel lymph nodes in the rat: noninvasive photoacoustic and US imaging with a clinical US system,” Radiology. 2010 Jul; 256(1): 102–110.
[8] Krishnamurthy S, Sneige N, Bedi DG, et al, “Role of ultrasound-guided fine needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma,” Cancer 2002, 95 (5): 982–988.
[9] Holwitt DM, Swatske ME, Gillanders WE, et al, “Scientific Presentation Award: The combination of axillary ultrasound and ultrasound-guided biopsy is an accurate predictor of axillary stage in clinically node-negative breast cancer patients,” Am J Surg 2008, 196 (4): 477–482.
[10] Schoenfeld A, Luqmani Y, Smith D, et al, “Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction,” Cancer Res 1994, 54 (11): 2986–2990.
[11] Noguchi S, Aihara T, Nakamori S, et al, “The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction,” Cancer 1994, 74 (5): 1595–1600.
[12] http://photo.hanyu.iciba.com/upload/encyclopedia_2/14/76/bk_1476540c915954f7a766e760ef5ec17b_c9s258.jpg
[13] R. Weissleder, “Molecular imaging in cancer,” Science, vol. 312, no. 5777, pp. 1168–1171, 2006.
[14] Brancato B, Zappa M, Bricolo D, et al, “Role of ultrasound-guided fine needle cytology of axillary lymph nodes in breast carcinoma staging,” Radiol. Med. 2004, 108 (4): 345–355.
[15] Deurloo EE, Tanis PJ, Gilhuijs KGA, et al, “Reduction in the number of sentinel lymph node procedures by preoperative ultrasonography of the axilla in breast cancer,” Eur. J. Cancer 2003, 39(8):1068–1073.
[16] Weskott, Hans-Peter, and Elena Simona Ioanitescu, “Diagnostic Approach to Lymph Node Diseases in Ultrasound.”
[17] Wilson SR, Burns PN, “Microbubble-enhanced US in body imaging: what role?” Radiology 2010, 257: 24–39.
[18] Sever A, Jones S, Cox K, et al, “Preoperative localization of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasonography in patients with breast cancer,” Br J Surg 2009, 96:1295–1299.
[19] Sever AR, Mills P, Jones SE, et al, “Preoperative sentinel node identification with ultrasound using microbubbles in patients with breast cancer,” AJR 2011, 196: 251–256.
[20] Ali R. Sever, Philippa Mills, et al, “Preoperative needle biopsy of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasound in patients with breast cancer,” American Journal of Roentgenology 2012 199:2, 465–470.
[21] Mehrmohammadi M, Oh J, Mallidi S, Emelianov SY, “Pulsed magneto-motive ultrasound imaging using ultrasmall magnetic nanoprobes,” Molecular imaging 10.2 (2011): 102–110.
[22] R. Qiao, C. Yang, and M. Gao, “Superparamagnetic iron oxide nanoparticles: From preparations to in vivo MRI applications,” J. Mater. Chem. 2009, vol. 19, no. 35, pp. 6274–6293.
[23] Tobias Neuberger, Bernhard Schöpf, Heinrich Hofmann, et al, “Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system,” Journal of Magnetism and Magnetic Materials, Volume 293, Issue 1, May 2005, pages 483–496.
[24] Mallidi S, Luke GP, Emelianov S. "Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance," Trends in biotechnology, 2011; 29 (5): 213–221.
[25] Zhang HF, Maslov K, Stoica G, Wang LV, “Functional photoacoustic microscopy for high resolution and noninvasive in vivo imaging,” Nat Biotechnol 2006, 24 (7): 848–851.
[26] Wang X, Pang Y, Ku G, et al, “Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain,” Nat Biotechnol 2003, 21 (7): 803–806.
[27] R. Jain, P. Dandekar, and V. Patravale, “Diagnostic nanocarriers for sentinel lymph node imaging,” J. Control. Release 2009, vol. 138, no. 2, pp. 90–102.
[28] J. Oh, M. D. Feldman, J. Kim, C. Condit, et al, “Detection of magnetic nanoparticles in tissue using magneto-motive ultrasound,” Nanotechnology, vol. 17, no. 16, pp. 4183–4190, 2006.
[29] Pei-Hsien Ting, Yi-Da Kang, San-Yuan Chen, Meng-Lin Li, “Ultrafast plane wave imaging based pulsed magnetomotive ultrasound,” IEEE Ultrasonics Symposium, 2014.
[30] Tanter M1, Bercoff J, Athanasiou A, et al, “Quantitative assessment of breast lesion viscoelasticity: initial clinical results using supersonic shear imaging,” Ultrasound Med Biol. 2008 Sep, 34 (9):1373–1386.
[31] McClain, Jacob, Sara L. Tuell, and Susan N. Thomas. “Tumors change the elastic and biscoelastic properties of draining lymph node tissues.” ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013.
[32] elzo, M.R.; Gallippi, C.M., “Viscoelastic response (VisR) imaging for assessment of viscoelasticity in voigt materials,” in Ultrasonics, Ferroelectrics, and Frequency Control, IEEE Transactions on , vol.60, no.12, pp.2488–2500, Dec. 2013.
[33] Mehrmohammadi M, Oh J, Mallidi S, Emelianov SY, “Pulsed magneto-motive ultrasound imaging using ultrasmall magnetic nanoprobes,” Molecular imaging. 2011;10(2):102-110.
[34] B. H. Friemel, L. N. Bohs, and G. E. Trahey, “Relative performance of two-dimensional speckle-tracking techniques: Normalized correlation, non-normalized correlation, and SAD,” IEEE Ultrasonics Symposium, 1995, pp. 1481–1484.
[35] A. S. Teja, P. Y. Koh, “Synthesis, properties, and applications of magnetic iron oxide nanoparticles,” Progress in Crystal Growth and Characterization of Materials, 55 (1–2), 2009.
[36] The original uploader was Sunshineconnelly at English Wikibooks.
[37] Oliveira Filho, Renato Santos de, Paiva, Geruza Rezende, et al, “Experimental model in rat for sentinel node biopsy,” Acta Cirurgica Brasileira 2003, vol. 18(spe), pp. 15–21.