Abstract
Detailed characterization of the tumor vasculature provides a better understanding of the complex mechanisms associated with tumor development and is especially important to evaluate responses to current therapies which target the tumor vasculature. Magnetic resonance imaging (MRI) studies of tumors have been mostly performed using gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) contrast-enhanced imaging, which relies on Gd-DTPA leakage from hyperpermeable tumor vessels and subsequent accumulation in the tumor interstitium. In certain tumor types, especially diffuse glioma in the brain, incorporated tumor vessels are not necessarily leaky, complicating effective diagnosis via Gd-DTPA contrast-enhanced MRI. Another class of contrast agents, based on superparamagnetic ultrasmall iron oxide particles (USPIO), allows for non-invasive assessment of vascular volume within the tumor. Vascular volume can be obtained by calculating the change in water proton transverse relaxation rate (R 2 or R 2*) following USPIO administration. This allows for an objective comparison between vascular volumes of different tumors and also allows to perform longitudinal studies in order to assess, for example, treatment efficacy. Moreover, since the USPIO T 2 relaxivity is up to 20 times that of Gd-DTPA, USPIO provides a highly sensitive marker for alterations in vascular volume among tissues; this characteristic might be exploited for tumor detection. Thus, USPIO imaging may be a very attractive alternative to the most commonly used Gd-DTPA imaging and will at least have added value, especially for detection and delineation of diffuse infiltrative brain tumors.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsSpringer Nature is developing a new tool to find and evaluate Protocols. Learn more
References
Folkman, J. (1992) The role of angiogenesis in tumor growth. Semin Cancer Biol 3, 65–71.
Kusters, B., Leenders, W. P., Wesseling, P., Smits, D., Verrijp, K., Ruiter, D. J., Peters, J. P., van Der Kogel, A. J., and de Waal, R. M. (2002) Vascular endothelial growth factor-A(165) induces progression of melanoma brain metastases without induction of sprouting angiogenesis. Cancer Res 62, 341–345.
Leenders, W. P., Kusters, B., Verrijp, K., Maass, C., Wesseling, P., Heerschap, A., Ruiter, D., Ryan, A., and de Waal, R. M. (2004) Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor progression via vessel co-option. Clin Cancer Res 10, 6222–6230.
Leenders, W. P., Kusters, B., Pikkemaat, J., Wesseling, P., Ruiter, D., Heerschap, A., Barentsz, J., and de Waal, R. M. (2003) Vascular endothelial growth factor-A determines detectability of experimental melanoma brain metastasis in GD-DTPA-enhanced MRI. Int J Cancer 105, 437–443.
Claes, A., Gambarota, G., Hamans, B., van Tellingen, O., Wesseling, P., Maass, C., Heerschap, A., and Leenders, W. P. (2008) Magnetic resonance imaging-based detection of glial brain tumors in mice after antiangiogenic treatment. Int J Cancer 122, 1981–1986.
Dennie, J., Mandeville, J. B., Boxerman, J. L., Packard, S. D., Rosen, B. R., and Weisskoff, R. M. (1998) NMR imaging of changes in vascular morphology due to tumor angiogenesis. Magn Reson Med 40, 793–799.
Le Duc, G., Peoc’h, M., Remy, C., Charpy, O., Muller, R. N., Le Bas, J. F., and Decorps, M. (1999) Use of T2-weighted susceptibility contrast MRI for mapping the blood volume in the glioma-bearing rat brain. Magn Reson Med 42, 754–761.
Tropres, I., Grimault, S., Vaeth, A., Grillon, E., Julien, C., Payen, J. F., Lamalle, L., and Decorps, M. (2001) Vessel size imaging. Magn Reson Med 45, 397–408.
Bremer, C., Mustafa, M., Bogdanov, A., Ntziachristos, V., Petrovsky, A., and Weissleder, R. (2003) Steady-state blood volume measurements in experimental tumors with different angiogenic burdens—a study in mice Radiology 226, 214–206.
Gambarota, G., van Laarhoven, H. W., Philippens, M., Lok, J., van der Kogel, A., Punt, C. J., and Heerschap, A. (2006) Assessment of absolute blood volume in carcinoma by USPIO contrast-enhanced MRI. Magn Reson Imaging 24, 279–286.
Weisskoff, R. M., Zuo, C. S., Boxerman, J. L., and Rosen, B. R. (1994) Microscopic susceptibility variation and transverse relaxation: theory and experiment. Magn Reson Med 31, 601–610.
Kennan, R. P., Zhong, J., and Gore, J. C. (1994) Intravascular susceptibility contrast mechanisms in tissues. Magn Reson Med 31, 9–21.
Kusters, B., Westphal, J. R., Smits, D., Ruiter, D. J., Wesseling, P., Keilholz, U., and de Waal R. M. (2001) The pattern of metastasis of human melanoma to the central nervous system is not influenced by integrin alpha(v)beta(3) expression. Int J Cancer 92, 176–180.
Gambarota, G., Leenders, W. P., Maass, C., Wesseling, P., van der Kogel, A. J., van Tellingen, O., and Heerschap, A. (2008) Characterisation of tumour vasculature in mouse brain by USPIO contrast-enhanced MRI. Br J Cancer 98, 1784–1789.
Enochs, W. S., Harsh, G., Hochberg, F., and Weissleder, R. (1999) Improved delineation of human brain tumors on MR images using a long-circulating, superparamagnetic iron oxide agent. J Magn Reson Imaging 9, 228–232.
Taschner, C. A., Wetzel, S. G., Tolnay, M., Froehlich, J., Merlo, A., and Radue, E. W. (2005) Characteristics of ultrasmall superparamagnetic iron oxides in patients with brain tumors. AJR Am J Roentgenol 185, 1477–1486.
Varallyay, P., Nesbit, G., Muldoon, L. L., Nixon, R. R., Delashaw, J., Cohen, J. I., Petrillo, A., Rink, D., and Neuwelt, E. A. (2002) Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors. AJNR Am J Neuroradiol 23, 510–519.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Gambarota, G., Leenders, W. (2011). Characterization of Tumor Vasculature in Mouse Brain by USPIO Contrast-Enhanced MRI. In: Schröder, L., Faber, C. (eds) In vivo NMR Imaging. Methods in Molecular Biology, vol 771. Humana Press. https://doi.org/10.1007/978-1-61779-219-9_25
Download citation
DOI: https://doi.org/10.1007/978-1-61779-219-9_25
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-218-2
Online ISBN: 978-1-61779-219-9
eBook Packages: Springer Protocols