Metastasis, the spread of a primary cancer to distant organs, continues to be the most significant cause of cancer mortality. Isolated primary tumors can often be treated surgically with a relatively high success rate. However, if the primary tumor has invaded the surrounding tissue and metastasized to secondary sites in the body, treatment options are often limited to systemic chemotherapies with much lower success rates and greater toxicity. Thus, it is imperative that a greater understanding of the biology of the metastatic process be acquired in order to achieve a significant reduction in the morbidity and mortality associated with cancer diagnosis.
The process of metastasis consists of multiple biological steps governed by a wide range of molecular processes (Chambers et al., 2002). The cells in a developing primary tumor must invade the surrounding tissue and gain access to a blood or lymphatic vessel to facilitate dissemination. Once the metastatic cell has arrived at a secondary site, the cell must arrest in the vascular system, survive, undergo cell division in the new microenvironment, and eventually recruit new blood vessels to allow for continued development. Although many cells initiate this sequence of events by gaining access to the vascular system, < 1% of these cells are able to complete all of the steps to form overt metastases (Chambers et al., 2002). The multi-step nature and biological and molecular complexity of the metastatic process have necessitated that a variety of research tools be used to effectively model this process. In vitro models have allowed for a greater understanding of how tumor cells circumvent normal cell growth and survival regulations. In vitro models are essential to isolate the contribution of specific molecular pathways to the development of a metastatic cell, but fail to capture the complexity of the entire metastatic process that exists in the in vivo situation. Thus, in order to study the complete metastatic process it is necessary to develop and utilize animal models. Animal models are used to study the interactions of a tumor cell with a changing micro-environment as it progresses through the metastatic process, and are often used to evaluate novel therapeutics and treatment strategies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Albrecht, T., Hohmann, J., Oldenburg, A., Skrok, J., and Wolf, K.J. 2004. Detection and characterisation of liver metastases. Eur. Radiol. 14 Suppl. 8:P25–P33.
Anwer, K., Kao, G., Proctor, B., Anscombe, I., Florack, V., Earls, R., Wilson, E., McCreery, T., Unger, E., Rolland, A., and Sullivan, S.M. 2000. Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration. Gene Ther. 7:1833–1839.
Blankenberg, F.G., Katsikis, P.D., Tait, J.F., Davis, R.E., Naumovski, L., Ohtsuki, K., Kopiwoda, S., Abrams, M.J., Darkes, M., Robbins, R.C., Maecker, H.T., and Strauss, H.W. 1998. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc. Natl. Acad. Sci. U S A 95:6349–6354.
Cai, S.R., Garbow, J.R., Culverhouse, R., Church, R.D., Zhang, W., Shannon, W.D., and McLeod, H.L. 2005. A mouse model for developing treatment for secondary liver tumors. Int. J. Oncol. 27:113–120.
Chambers, A.F., MacDonald, I.C., Schmidt, E.E., Koop, S., Morris, V.L., Khokha, R., and Groom, A.C. 1995. Steps in tumor metastasis: new concepts from intravital videomicroscopy. Cancer Metastasis Rev. 14:279–301.
Chambers, A.F., Groom, A.C., and MacDonald, I.C. 2002. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2:563–572.
Cheung, A.M., Brown, A.S., Hastie, L.A., Cucevic, V., Roy, M., Lacefield, J.C., Fenster, A., and Foster, F.S. 2005. Three-dimensional ultrasound biomicroscopy for xenograft growth analysis. Ultrasound Med. Biol. 31:865–870.
Choy, G., Choyke, P., and Libutti, S.K. 2003. Current advances in molecular imaging: non-invasive in vivo bioluminescent and fluorescent optical imaging in cancer research. Mol. Imaging 2:303–312.
Couture, O., Bevan, P.D., Cherin, E., Cheung, K., Burns, P.N., and Foster, F.S. 2006. Investigating perfluorohexane particles with high-frequency ultrasound. Ultrasound Med. Biol. 32:73–82.
Dayton, P.A., and Ferrara, K.W. 2002. Targeted imaging using ultrasound. J. Magn. Reson. Imaging 16:362–377.
Demicheli, R., Terenziani, M., and Bonadonna, G. 1998. Estimate of tumor growth time for breast cancer local recurrences: rapid growth after wake-up? Breast Cancer Res. Treat. 51: 133–137.
Ellegala, D.B., Leong-Poi, H., Carpenter, J.E., Klibanov, A.L., Kaul, S., Shaffrey, M.E., Sklenar, J., and Lindner, J.R. 2003. Imaging tumor ang-iogenesis with contrast ultrasound and micro-bubbles targeted to alpha(v)beta3. Circulation 108:336–341.
Evelhoch, J.L., Gillies, R.J., Karczmar, G.S., Koutcher, J.A., Maxwell, R.J., Nalcioglu, O., Raghunand, N., Ronen, S.M., Ross, B.D., and Swartz, H.M. 2000. Applications of magnetic resonance in model systems: cancer therapeutics. Neoplasia 2:152–165.
Fenster, A., Downey, D.B., and Cardinal, H.N. 2001. Three-dimensional ultrasound imaging. Phys. Med. Biol. 46:R67–R99.
Foster, F.S., Pavlin, C.J., Harasiewicz, K.A., Christopher, D.A., and Turnbull, D.H. 2000. Advances in ultrasound biomicroscopy. Ultrasound Med. Biol. 26:1–27.
Foster, F.S., Zhang, M.Y., Zhou, Y.Q., Liu, G., Mehi, J., Cherin, E., Harasiewicz, K.A., Starkoski, B.G., Zan, L., Knapik, D.A., and Adamson, S.L. 2002. A new ultrasound instrument for in vivo microimaging of mice. Ultrasound Med. Biol. 28:1165–1172.
Gambhir, S.S. 2002. Molecular imaging of cancer with positron emission tomography. Nat. Rev. Cancer 2: 683–693.
Gillies, R.J., Bhujwalla, Z.M., Evelhoch, J., Garwood, M., Neeman, M., Robinson, S.P., Sotak, C.H., and Van Der Sanden, B. 2000. Applications of magnetic resonance in model systems: tumor biology and physiology. Neoplasia 2:139–151.
Goertz, D.E., Yu, J.L., Kerbel, R.S., Burns, P.N., and Foster, F.S. 2002. High-frequency Doppler ultrasound monitors the effects of antivascu-lar therapy on tumor blood flow. Cancer Res. 62:6371–6375.
Goertz, D.E., Yu, J.L., Kerbel, R.S., Burns, P.N., and Foster, F.S. 2003. High-frequency 3-D color-flow imaging of the microcirculation. Ultrasound Med. Biol. 29:39–51.
Goertz, D.E., Cherin, E., Needles, A., Karshafian, R., Brown, A.S., Burns, P.N., and Foster, F.S. 2005. High frequency nonlinear B-scan imaging of microbubble contrast agents. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 52:65–79.
Graham, K.C., Wirtzfeld, L.A., MacKenzie, L.T., Postenka, C.O., Groom, A.C., MacDonald, I.C., Fenster, A., Lacefield, J.C., and Chambers, A.F. 2005. Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models. Cancer Res. 65:5231–5237.
Hastie, L.A., Graham, K.C., Groom, A.C., MacDonald, I.C., Chambers, A.F., Fenster, A., and Lacefield, J.C. 2004. Variability of three-dimensional high-frequency ultrasound measurements of small tumor volumes. IEEE Ultrason. Sympos. Proc. 3:2185–2188.
Heyn, C., Ronald, J.A., Mackenzie, L.T., MacDonald, I.C., Chambers, A.F., Rutt, B.K., and Foster, P.J. 2006. In vivo magnetic resonance imaging of single cells in mouse brain with optical validation. Magn. Reson. Med. 55:23–29.
Holmgren, L., O'Reilly, M.S., and Folkman, J. 1995. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat. Med. 1: 149–153.
Karrison, T.G., Ferguson, D.J., and Meier, P. 1999. Dormancy of mammary carcinoma after mastectomy. J. Natl. Cancer Inst. 91:80–85.
Khanna, C., and Hunter, K. 2005. Modeling metastasis in vivo. Carcinogenesis 26:513–523.
Kobayashi, H., Saga, T., Kawamoto, S., Sato, N., Hiraga, A., Ishimori, T., Konishi, J., Togashi, K., and Brechbiel, M.W. 2001. Dynamic micro-magnetic resonance imaging of liver micrometas-tasis in mice with a novel liver macromolecular magnetic resonance contrast agent DAB-Am64-(1B4M-Gd)(64). Cancer Res. 61:4966–4970.
Kolios, M.C., Czarnota, G.J., Lee, M., Hunt, J.W., and Sherar, M.D. 2002. Ultrasonic spectral parameter characterization of apoptosis. Ultrasound Med. Biol. 28:589–597.
Krix, M., Kiessling, F., Vosseler, S., Farhan, N., Mueller, M.M., Bohlen, P., Fusenig, N.E., and Delorme, S. 2003. Sensitive noninvasive monitoring of tumor perfusion during antiang-iogenic therapy by intermittent bolus-contrast power Doppler sonography. Cancer Res. 63: 8264–8270.
Lanza, G.M., Wallace, K.D., Fischer, S.E., Christy, D.H., Scott, M.J., Trousil, R.L., Cacheris, W.P., Miller, J.G., Gaffney, P.J., and Wickline, S.A. 1997. High-frequency ultrasonic detection of thrombi with a targeted contrast system. Ultrasound Med. Biol. 23:863–870.
Lawrie, A., Brisken, A.F., Francis, S.E., Cumberland, D.C., Crossman, D.C., and Newman, C.M. 2000. Microbubble-enhanced ultrasound for vascular gene delivery. Gene Ther. 7:2023–2027.
Leach, M.O. 2001. Application of magnetic resonance imaging to angiogenesis in breast cancer. Breast Cancer Res. 3:22–27.
Lencioni, R., Pinto, F., Armillotta, N., and Bartolozzi, C. 1996. Assessment of tumor vascu-larity in hepatocellular carcinoma: comparison of power Doppler US and color Doppler US. Radiology 201:353–358.
Lindner, J.R. 2004. Microbubbles in medical imaging: current applications and future directions. Nat. Rev. Drug Discov. 3:527–532.
Lyons, S.K. 2005. Advances in imaging mouse tumour models in vivo. J. Pathol. 205:194–205.
Mazonakis, M., Damilakis, J., Mantatzis, M., Prassopoulos, P., Maris, T., Varveris, H., and Gourtsoyiannis, N. 2004. Stereology versus planimetry to estimate the volume of malignant liver lesions on MR imaging. Magn. Reson. Imaging 22:1011–1016.
Miller, D.L., and Quddus, J. 2000. Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice. Proc. Natl. Acad. Sci. U S A 97:10179–10184.
Morris, V.L., MacDonald, I.C., Koop, S., Schmidt, E.E., Chambers, A.F., and Groom, A.C. 1993. Early interactions of cancer cells with the microvasculature in mouse liver and muscle during hematogenous metastasis: videomi-croscopic analysis. Clin. Exp. Metastasis 11: 377–390.
Narula, J., Acio, E.R., Narula, N., Samuels, L.E., Fyfe, B., Wood, D., Fitzpatrick, J.M., Raghunath, P.N., Tomaszewski, J.E., Kelly, C., Steinmetz, N., Green, A., Tait, J.F., Leppo, J., Blankenberg, F.G., Jain, D., and Strauss, H.W. 2001. Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nat. Med. 7:1347–1352.
Paulus, M.J., Gleason, S.S., Kennel, S.J., Hunsicker, P.R., and Johnson, D.K. 2000. High resolution X-ray computed tomography: an emerging tool for small animal cancer research. Neoplasia 2:62–70.
Price, R.J., Skyba, D.M., Kaul, S., and Skalak, T.C. 1998. Delivery of colloidal particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound. Circulation 98:1264–1267.
Steinbauer, M., Guba, M., Cernaianu, G., Kohl, G., Cetto, M., Kunz-Schughart, L.A., Geissler, E.K., Falk, W., and Jauch, K.W. 2003. GFP-transfected tumor cells are useful in examining early metastasis in vivo, but immune reaction precludes long-term tumor development studies in immunocompetent mice. Clin. Exp. Metastasis 20:135–141.
Tong, S., Cardinal, H.N., McLoughlin, R.F., Downey, D.B., and Fenster, A. 1998. Intra- and inter-observer variability and reliability of prostate volume measurement via two-dimensional and three-dimensional ultrasound imaging. Ultrasound Med. Biol. 24:673–681.
Tunis, A.S., Czarnota, G.J., Giles, A., Sherar, M.D., Hunt, J.W., and Kolios, M.C. 2005. Monitoring structural changes in cells with high-frequency ultrasound signal statistics. Ultrasound Med. Biol. 31:1041–1049.
Turnbull, D.H., Ramsay, J.A., Shivji, G.S., Bloomfield, T.S., From, L., Sauder, D.N., and Foster, F.S. 1996. Ultrasound backscatter microscope analysis of mouse melanoma progression. Ultrasound Med. Biol. 22:845–853.
Udagawa, T., Fernandez, A., Achilles, E.G., Folkman, J., and D'Amato, R.J. 2002. Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy. FASEB J. 16:1361–1370.
Unger, E.C., Matsunaga, T.O., McCreery, T., Schumann, P., Sweitzer, R., and Quigley, R. 2002. Therapeutic applications of microbubbles. Eur. J. Radiol. 42:160–168.
Weber, S.M., Peterson, K.A., Durkee, B., Qi, C., Longino, M., Warner, T., Lee, F.T., Jr., and Weichert, J.P. 2004. Imaging of murine liver tumor using microCT with a hepatocyte-selective contrast agent: accuracy is dependent on adequate contrast enhancement. J. Surg. Res. 119:41–45.
Weissleder, R. 2002. Scaling down imaging: molecular mapping of cancer in mice. Nat. Rev. Cancer 2:11–18.
Welch, D.R. 1997. Technical considerations for studying cancer metastasis in vivo. Clin. Exp. Metastasis 15:272–306.
Weller, G.E., Wong, M.K., Modzelewski, R.A., Lu, E., Klibanov, A.L., Wagner, W.R., and Villanueva, F.S. 2005. Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine. Cancer Res. 65:533–539.
Wirtzfeld, L.A., Wu, G., Bygrave, M., Yamasaki, Y., Sakai, H., Moussa, M., Izawa, J.I., Downey, D.B., Greenberg, N.M., Fenster, A., Xuan, J.W., and Lacefield, J.C. 2005. A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model. Cancer Res. 65: 6337–6345.
Wu, M., Mazurchuk, R., Chaudhary, N.D., Spernyak, J., Veith, J., Pera, P., Greco, W., Hoffman, R.M., Kobayashi, T., and Bernacki, R.J. 2003. High-resolution magnetic resonance imaging of the efficacy of the cytosine analogue 1-[2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl]-N(4)-palmitoyl cytosine (CS-682) in a liver-metastasis athymic nude mouse model. Cancer Res. 63:2477–2482.
Xu, H.X., Yin, X.Y., Lu, M.D., Liu, G.J., and Xu, Z.F. 2003. Estimation of liver tumor volume using a three-dimensional ultrasound volumetric system. Ultrasound Med. Biol. 29:839–846.
Yang, M., Baranov, E., Jiang, P., Sun, F.X., Li, X.M., Li, L., Hasegawa, S., Bouvet, M., Al-Tuwaijri, M., Chishima, T., Shimada, H., Moossa, A.R., Penman, S., and Hoffman, R.M. 2000. Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc. Natl. Acad. Sci. U S A 97:1206–1211.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science + Business Media B.V.
About this chapter
Cite this chapter
Graham, K.C., Wirtzfeld, L.A., Lacefield, J.C., Chambers, A.F. (2009). Preclinical Liver Metastases: Three-Dimensional High-Frequency Ultrasound Imaging. In: Hayat, M.A. (eds) Liver Cancer. Methods of Cancer Diagnosis, Therapy and Prognosis, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9804-8_29
Download citation
DOI: https://doi.org/10.1007/978-1-4020-9804-8_29
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-9803-1
Online ISBN: 978-1-4020-9804-8
eBook Packages: MedicineMedicine (R0)