Xu Gaixia,Zhai Peng,Lin Suxia,et al.The applications of tumor in vivo imaging by using transparent dorsal skin fold window chamber[J].Journal of Shenzhen University Science and Engineering,2013,30(No.5(441-550)):518-526.[doi:10.3724/SP.J.1249.2013.05518]





The applications of tumor in vivo imaging by using transparent dorsal skin fold window chamber
许改霞1 翟鹏2 林苏霞2 饶南熹1 朱小妹1 王晓梅2 牛憨笨1
2)深圳大学医学院,深圳市生物医学工程重点实验室,深圳 518060
Xu Gaixia1 Zhai Peng2 Lin Suxia2 Rao Nanxi1 Zhu Xiaomei1 Wang Xiaomei2 and Niu Hanben1
1) College of Optoelectric Engineering, Key Laboratory of Optoelectronic Devices and System of Ministry of Education and Guangdong Province, Shenzhen University, Shenzhen 518060, P.R.China
2) College of Medicine, Shenzhen Key Laboratory of Biomedical Engineering, Shenzhen University, Shenzhen 518060, P.R.China
biophysics dorsal skin fold window chamber in vivo imaging optical imaging tumor research angiogenesis
R 332
This paper introduces the history and characteristics of dorsal skin fold window chamber (DSFC), a novel optical in vivo imaging auxiliary tool. Then, the construction and the optical in vivo imaging systems based on the DSFC are summarized. The main applications for tumor optical in vivo imaging of DSFC are presented. Finally, it is pointed out that the DSFC has great potential for cancer angiogenesis and the mechanism of cancer development by in situ, real-time and long-term optical in vivo imaging.


[1] Judah F. Tumor angiogenesis: therapeutic implications[J]. New England Journal of Medicine, 1971, 285(21): 1182-1186.
[2] Branemark P L, Aspegren K, Breine U. Microcirculatory studies in man by high resolution vital microscopy[J]. Angiology, 1964, 15(8): 329-332.
[3] Beverly A T. Tumor Models in Cancer Research[M]. 2nd ed. New York: Humana Press, 2011: 641-679.
[4] Gudrun E K, Andreas G, Edward K G. Intravital microscopy of tumor angiogenesis and regression in the dorsal skin fold chamber: mechanistic insights and preclinical testing of therapeutic strategies[J]. Clinical & Experimental Metastasis, 2009, 26(4): 329-344.
[5] Arfors K E, Jonsson J A, McKenzie F N. A titanium rabbit ear chamber: assembly, insertion and results[J]. Microvascular Research, 1970, 2(4): 516-518.
[6] Eddy H A, Casarett G W. Development of the vascular system in the hamster malignant neurilemmoma[J]. Microvascular Research, 1973,6(1): 63-82.
[7] Yuan F, Salehi H A, Boucher Y, et al. Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows[J]. Cancer Research, 1994, 54(17): 4564-4568.
[8] Tam J, Duda D G, Perentes J Y, et al. Blockade of VEGFR2 and not VEGFR1 can limit diet-induced fat tissue expansion: role of local vers us bone marrow-derived endothelial cells[J]. PLoS One, 4(3): e4974-1-e4974-6.
[9] Milan M. Intravital imaging and cell invasion[J]. Methods in Enzymology, 2007, 426: 375-401.
[10] Gregory M P, Andrew N F, Shan S Q, et al. In vivo optical molecular imaging and analysis in mice using dorsal window chamber models applied to hypoxia, vasculature and fluorescent reporters[J]. Nature Protocols, 2011, 6(9): 1355-1366.
[11] Takashi C, Yohei M, Li L N, et al. Use of histoculture and green fluorescent protein to visualize tumor cell host interaction[J]. In Vitro Cellular & Developmental Biology-Animal,1997, 10(33): 745-747.
[12] Masaaki K, Hideo H, Motohiro T, et al. Dynamics of different-sized solid-state nanocrystals as tracers for a drug-delivery system in the interstitium of a human tumor xenograft[J]. Breast Cancer Research, 2009, 11(4): R43-1-R43-9.
[13] Li C Y, Shan S Q, Cao Y T, et al. Role of incipient angiogenesis in cancer metastasis[J]. Cancer and Metastasis Reviews, 2000, 19(1/2): 7-11.
[14] Rakesh K J, Lance L M, Dai F. Dissecting tumor pathophysiology using intravital microscopy[J]. Nature Review Cancer, 2002, 2(4): 266-276.
[15] Matthew R D, Liu W G, Charles R M, et al. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers[J]. Journal of the National Cancer Institute, 2006, 98(5): 335-344.
[16] Makale M T, Chen P C, David A G. Variants of the tissue-sensor array window chamber[J]. American Journal of Physiology Heart and Circulatory Physiology, 2005, 289(1): 57-65.
[17] Matthew R D, Liu W G, Charles R M, et al. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers[J]. Journal of the National Cancer Institute, 2006, 98(5): 335-344.
[18] Mamta W, Casey D, Dietmar W S, et al. In vivo functional differences in microvascular response of 4T1 and Caki-1 tumors after treatment with OXi4503[J]. Oncology Reports, 2010, 23(3): 685-692.
[19] Hsiang K Y, Christopher G K, Christy M W, et al. In vivo particle tracking and photothermal ablation using plasmon-resonant gold nanostars[J]. Nanomedicine: Nanotechnology, Biology, and Medicine, 2012, 8(8): 1355-1363.
[20] Gu Xiang, Liu Xiaoxia, Sun Jianqi. Synchrotron radiation imaging technology in tumor new blood vessels experimental research[J]. Nuclear Technology, 2009, 32(7) :487-492.(in Chinese)
顾翔,刘晓霞,孙建奇. 同步辐射成像技术应用于肿瘤新生血管的实验初探[J]. 核技术,2009,32(7):487-492.
[21] Liu Ping, Xu Xuemin, Zhang Aili, et al. Applied research of thermal physics in tumor therapy and nano particles for targeted drug delivery[J]. Chinese Journal of Biomedical Engineering, 2005,24(2):212-216.(in Chinese)
刘苹,徐学敏, 张爱丽, 等.热物理在肿瘤治疗及纳米药物靶向输送方面的应用研究[J].中国生物医学工程学报,2005,24(2):212-216.
[22] Zhang G Q, Gregory M P, Mark W D, et al. A dual-emissive-materials design concept enables tumor hypoxia imaging[J]. Nature Materials, 2009(8):747-751.
[23] Zhong G G, Tian L, Hu J. Prevention of metastasis in a 4T1 murine breast cancer model by doxorubicin carried by folate conjugated pH sensitive polymeric micelles[J]. Journal of Controlled Release,2011,152(1): 84-89.
[24] Bernard C, Nicole M K, Nelson J S. Laser speckle imaging for monitoring blood flow dynamics in the in vivo rodent dorsal skin fold model[J]. Microvascular Research, 2004,68(2): 143-146.
[25] Tozer G M, Ameer-Beg S M, Baker J, et al. Intravital imaging of tumor vascular networks using multi-photon fluorescencemicroscopy[J]. Advanced Drug Delivery Reviews, 2005, 57(1): 135-152.
[26] Wofgang D, James G F. Optical Coherence Tomography: Technology and Applications[M]. New York: Springer Press, 2008: 209-287.
[27] Benjamin J V, Ryan M L, James A T, et al. Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging[J]. Nature Medicine, 2009, 15(10): 1219-1223.
[28] Ding Zhihua, Chen Minghui, Wang Kai, et al. Quick sweep frequency light source and its in optical frequency domain the applications imaging[J]. Chinese Journal of Lasers, 2009,36(10):2469-2476.(in Chinese).
丁志华, 陈明惠, 王凯, 等.快速扫频光源及其在光学频域成像中的应用[J].中国激光, 2009,36(10):2469-2476.
[29] Tsuzuki Y, Fukumura D, Oosthuyse B, et al. Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia inducible factor-1α → hypoxia response element → VEGF cascade differentially regulates vascular response and growthrate in tumors[J]. Cancer Research, 2000, 60: 6248-6252.
[30] Debergh, Van D N, Pattyn P, et al. The low-molecular-weight heparin, nadroparin, inhibits tumor angiogenesis in a rodent dorsal skin fold chamber model[J]. British Journal of Cancer, 2010, 102:837-843.
[31] Melissa C S, Andrew F, Lan L, et al. Longitudinal optical imaging of tumor metabolism and hemodynamics[J]. Journal of Biomedical Optics, 2010,15(1): 011112.
[32] Heddlestonl J M, Li Z, Lathia J D, et al. Hypoxia inducible factors in cancer stem cells[J]. British Journal of Cancer, 2010, 102: 789 -795.
[33] Kashiwagi S, Izumi Y, Gohongi T, et al. NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels[J]. Journal of Clinical Investigation, 2005, 115(7): 1816-1827.
[34] Kashiwagi S, Tsukada K, Xu L, et al. Perivascular nitric oxide gradients normalize tumor vasculature[J]. Nature Medicine, 2008, 14(3): 255-257.
[35] Hansen-Algenstaedt N, Stoll B R, Padera T P, et al. Tumor oxygenation during VEGF-R2 blockage, hormone ablation, and chemotherapy[J]. Cancer Research, 2000, 60(16): 4556-4560.
[36] Martin N A, Gaffney E A, Gatenby R A, et al. Leaky vessels as a potential source of stromal acidification in tumours[J]. Journal of Theoretical Biology, 2010, 267(3): 454-460.
[37] Ondeelis J, Singer Rt H, Segall J E. The great escape: when cancer cells hijack the genes for chemotaxis and motility[J]. Annual Review of Cell and Developmental Biology, 2005,21:695-718.
[38] Dewhirst M W, Shan S, Cao Y T, et al. Intravital fluorescence facilitates measurement of multiple physiologic functions and gene expression in tumors of live animals[J]. Disease Markers, 2002,18(5/6): 293-311.
[39] Mark W Dt, Yiting C, Li C Y, et al. Exploring the role of HIF-1 in early angiogenesis and response to radiotherapy[J]. Radiotherapy and Oncology, 2007, 83(3): 249-255.
[40] Gregory M P, Andrew N F, Zhang G Q, et al. Optical imaging of tumor hypoxia dynamics[J]. Journal of Biomedical Optics, 2010,15(6): 066021-1-066021-7.
[41] Wen Chongwei, Ning Degang, Liu Ruijiang, et al. A novel target for starving tumor therapy: endocrine-gland-derived vascular endothelial growth factor[J]. Progress in Biochemistry and Biophysics, 2011, 38(1): 5-10. (in Chinese)
闻崇炜, 宁德刚, 刘瑞江, 等. 肿瘤饥饿疗法的新靶标: 内分泌腺衍生血管内皮生长因子[J].生物化学与生物物理学进展, 2011, 38(1): 5-10.
[42] Nie S M, Xing Y, Gloria J K, et al. Nanotechnology applications in cancer[J]. Annual Review of Biomedical Engineering, 2007,9: 257-288.
[43] Resch-Genger U, Grabolle M, Cavaliere-Jaricot M, et al. Quantum dots versus organic dyes as fluorescent labels[J]. Nature Methods, 2008, 5(9): 763-775.
[44] Chan W C W, Nie S M. Quantum dot bioconjugates for ultrasensitive nonisotopic detection[J]. Science,1998, 281(5385): 2016-2018.
[45] Michale X, Pinaud F F, Bentolila L A, et al. Quantum dots for live cells, in vivo imaging, and diagnostics[J]. Science, 2005, 307(5709): 538-544.
[46] Smith A M, Nie S M. Next-generation quantum dots[J]. Nature Biotechnology, 2009, 27(8): 732-733.
[47] So M K, Xu C J, Loening A M, et al. Self-illuminating quantum dot conjugates for in vivo imaging[J]. Nature Biotechnology, 2006, 24(3): 339-343.
[48] Tada H, Higuchi H, Wanatabe T M, et al. In vivo real-time tracking of single quantum dots conjugated with monoclonal anti-HER2 antibody in tumors of mice[J]. Cancer Research, 2007, 67(3): 1138-1144.
[49] Stroh M, Zimmer J P, Duda D G, et al. Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo[J]. Nature Medicine, 2005, 11(6): 678-682.
[50] Voura E B, Jaiswal J K, Mattoussi H, et al. Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy[J]. Nature Medicine, 2004,10(9):993-998.


 CHEN Si-ping,ZENG Si-ning,WANG Tian-fu,et al.Numerical simulation on acoustic radiation force induced by ultrasonic coded excitation[J].Journal of Shenzhen University Science and Engineering,2011,28(No.5(441-550)):165.


Foundation:National Basic Research Program of China(2012CB85802); Technological and Scientific Innovation Project of Guangdong Educational Commission(2012KJCX0094)
Corresponding author:Professor Wang Xiaomei. E-mail: xmwang@szu.edu.cn
Citation:Xu Gaixia, Zhai Peng, Lin Suxia, et al. The applications of tumor in vivo imaging by using transparent dorsal skin fold window chamber[J]. Journal of Shenzhen University Science and Engineering, 2013, 30(5): 518-526.(in Chinese)
作者简介:许改霞(1977-),女(汉族),内蒙古自治区巴彦淖尔市人,深圳大学副研究员、博士. E-mail: xugaixia@szu.edu.cn
引文:许改霞, 翟鹏, 林苏霞,等. 透明背脊皮翼视窗在肿瘤活体成像中的应用[J]. 深圳大学学报理工版,2013,30(5):518-526.
更新日期/Last Update: 2013-09-02