Abstract
The breadth and substance of anatomic (structural) and novel physiological (functional) imaging methods to noninvasively monitor and assess anticancer therapies continues to grow. Current techniques span several imaging disciplines including magnetic resonance (MR) imaging, positron emission tomography (PET), computed tomography (CT), ultrasound (US), and optical-based methods using fluorescence and bioluminescence techniques. These methodologies applied in the clinic and/or in animal models offer unique insights into disease processes. Applications affected by imaging include therapeutic response assessment, improved diagnostic evaluations, enhanced delineation of tumor boundaries, elucidation of the underlying mechanisms of therapeutic response and drug resistance, identification of high-risk subpopulations of transgenic animals with specific alterations in their genome leading to abnormal phenotypes, and prediction of therapeutic outcome. This chapter provides a brief introduction to this emerging field, focusing specifically on novel MR applications related to chemotherapeutic response assessment, step-by-step procedures to perform the outlined techniques, and algorithms to analyze resultant data.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gillies, R. J., Raghunand, N., Karczmar, G. S., and Bhujwalla, Z. M. (2002) MRI of the tumor microenvironment. J. Magn. Reson. Imaging 16, 430ā450.
Bhujwalla, Z. M., Artemov, D., Aboagye, E., et al. (2001) The physiological environment in cancer vascularization, invasion and metastasis. Novartis. Found. Symp. 240, 23ā38.
Bhujwalla, Z. M., Artemov, D., Ballesteros, P., Cerdan, S., Gillies, R. J., and Solaiyappan, M. (2002) Combined vascular and extracellular pH imaging of solid tumors. NMR Biomed. 15, 114ā119.
Ross, B. D., Zhao, Y. J., Neal, E. R., et al. (1998) Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: an MRI study. Proc. Natl. Acad. Sci. USA 95, 7012-7017.
Howe, F. A., Robinson, S. P., Rodrigues, L. M., and Griffiths, J. R. (1999) Flow and oxygenation dependent (FLOOD) contrast MR imaging to monitor the response of rat tumors to carbogen breathing. Magn. Reson. Imaging 17, 1307ā1318.
Robinson, S. P., Collingridge, D. R., Howe, F. A., Rodrigues, L. M., Chaplin, D. J., and Griffiths, J. R. (1999) Tumour response to hypercapnia and hyperoxia monitored by FLOOD magnetic resonance imaging. NMR Biomed. 12, 98ā106.
Griffiths, J. R. and Glickson, J. D. (2000) Monitoring pharmacokinetics of anticancer drugs: non-invasive investigation using magnetic resonance spectroscopy. Adv. Drug Deliv. Rev. 41, 75ā89.
Ackerstaff, E., Glunde, K., and Bhujwalla, Z. M. (2003) Choline phospholipid metabolism: a target in cancer cells? J. Cell Biochem. 90, 525ā533.
Bhujwalla, Z. M., Artemov, D., Natarajan, K., Ackerstaff, E., and Solaiyappan, M. (2001) Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts. Neoplasia 3, 143ā153.
Bhujwalla, Z. M., Artemov, D., Natarajan, K., Solaiyappan, M., Kollars, P., and Kristjansen, P. E. (2003) Reduction of vascular and permeable regions in solid tumors detected by macromolecular contrast magnetic resonance imaging after treatment with antiangiogenic agent TNP-470. Clin. Cancer Res. 9, 355ā362.
Lewin, M., Bredow, S., Sergeyev, N., Marecos, E., Bogdanov, A. Jr., and Weissleder, R. (1999) In vivo assessment of vascular endothelial growth factorinduced angiogenesis. Int. J. Cancer 83, 798ā802.
Weissleder, R. and Mahmood, U. (2001) Molecular imaging. Radiology 219, 316ā333.
Boxerman, J. L., Bandettini, P. A., Kwong, K. K., et al. (1995) The intravascular contribution to fMRI signal change: Monte Carlo modeling and diffusion-weighted studies in vivo. Magn. Reson. Med. 34, 4ā10.
Bandettini, P. A., Kwong, K. K., Davis, T. L., Tootell, R. B., Wong, E. C., and Fox, P. T. (1997) Characterization of cerebral blood oxygenation and flow changes during prolonged brain activation. Hum. Brain Mapp. 5, 93ā109.
Davis, T. L., Kwong, K. K., Weisskoff, R. M., and Rosen, B. R. (1998) Calibrated functional MRI: mapping the dynamics of oxidative metabolism. Proc. Natl. Acad. Sci. USA 95, 1834ā1839.
Howe, F. A., Robinson, S. P., McIntyre, D. J., Stubbs, M., and Griffiths, J. R. (2001) Issues in flow and oxygenation dependent contrast (FLOOD) imaging of tumours. NMR Biomed. 14, 497ā506.
Bott, G. (1985) Vasodilators and regional blood flow. Indian J. Pharmacol. 1985.
Mazurchuk, R., Zhou, R., Straubinger, R. M., Chau, R. I., and Grossman, Z. (1999) Functional magnetic resonance (fMR) imaging of a rat brain tumor model: implications for evaluation of tumor microvasculature and therapeutic response. Magn. Reson. Imaging 17, 537ā548.
Zhou, R., Mazurchuk, R., and Straubinger, R. M. (2002) Antivasculature effects of doxorubicin-containing liposomes in an intracranial rat brain tumor model. Cancer Res. 62, 2561ā2566.
Bhattacharya, A., Toth, K., Mazurchuk, R., et al. (2004) Lack of microvessels in well-differentiated regions of human head and neck squamous cell carcinoma A253 is associated with fMR imaging detectable hypoxia, limited drug delivery and resistance to irinotecan therapy. Clin. Cancer Res. 10, 8005ā8017.
Neeman, M. and Dafni, H. (2003) Structural functional, and molecular MR imaging of the microvasculature. Annu. Rev. Biomed. Eng. 5, 29ā56.
Neeman, M., Dafni, H., Bukhari, O., Braun, R. D., and Dewhirst, M. W.(2001) In vivo BOLD contrast MRI mapping of subcutaneous vascular function and maturation: validation by intravital microscopy. Magn. Reson. Med. 45, 887ā898.
Shaharabany, M., Abramovitch, R., Kushnir, T., et al. (2001) In vivo molecular imaging of met tyrosine kinase growth factor receptor activity in normal organs and breast tumors. Cancer Res. 61, 4873ā4878.
Artemov, D., Solaiyappan, M., and Bhujwalla, Z. M. (2001) Magnetic resonance pharmacoangiography to detect and predict chemotherapy delivery to solid tumors. Cancer Res. 61, 3039ā3044.
Fenton, B. M., Lord, E. M., and Paoni, S. F. (2000) Enhancement of tumor perfusion and oxygenation by carbogen and nicotinamide during single-and multifraction irradiation. Radiat. Res. 153, 75ā83.
Chenevert, T. L., Meyer, C. R., Moffat, B. A., et al. (2002) Diffusion MRI: a new strategy for assessment of cancer therapeutic efficacy. Mol. Imaging 1, 336ā343.
Ross, B. D., Moffat, B. A., Lawrence, T. S., et al. (2003) Evaluation of cancer therapy using diffusion magnetic resonance imaging. Mol. Cancer Ther. 2, 581ā587.
Chenevert, T. L., Stegman, L. D., Taylor, J. M., et al. (2000) Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. J. Natl. Cancer Inst. 92, 2029ā2036.
Stegman, L. D., Rehemtulla, A., Hamstra, D. A., et al. (2000) Diffusion MRI detects early events in the response of a glioma model to the yeast cytosine deaminase gene therapy strategy. Gene Ther. 7, 1005ā1010.
Chenevert, T. L., McKeever, P. E., and Ross, B. D. (1997) Monitoring early response of experimental brain tumors to therapy using diffusion magnetic resonance imaging. Clin. Cancer Res. 3, 1457ā1466.
Daldrup-Link, H. E. and Brasch, R. C. (2003) Macromolecular contrast agents for MR mammography: current status. Eur. Radiol. 13, 354ā365.
Choyke, P. L., Dwyer, A. J., and Knopp, M. V. (2003) Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging. J. Magn. Reson. Imaging 17, 509ā520.
Padhani, A. R. (2002) Dynamic contrast-enhanced MRI in clinical oncology: current status and future directions. J. Magn. Reson. Imaging 16, 407ā422.
Roberts, T. P., Turetschek, K., Preda, A., et al. (2002) Tumor microvascular changes to anti-angiogenic treatment assessed by MR contrast media of different molecular weights. Acad. Radiol. 9(Suppl. 2), S511āS513.
Roberts, T. P., Helbich, T. H., Ley, S., et al. (2002) Utility (or not) of Gd-DTPA-based dynamic MRI for breast cancer diagnosis and grading. Acad. Radiol. 9 (Suppl. 1), S261āS265.
Roberts, H. C., Roberts, T. P., Brasch, R. C., and Dillon, W. P. (2000) Quantitative measurement of microvascular permeability in human brain tumors achieved using dynamic contrast-enhanced MR imaging: correlation with histologic grade. Am. J. Neuroradiol. 21, 891ā899.
Gossmann, A., Helbich, T. H., Kuriyama, N., et al. (2002) Dynamic contrastenhanced magnetic resonance imaging as a surrogate marker of tumor response to anti-angiogenic therapy in a xenograft model of glioblastoma multiforme. J. Magn. Reson. Imaging 15, 233ā240.
Stiskal, M., Demsar, F., Muhler, A., et al. (1999) Contrast-enhanced MR imaging of two superparamagnetic RES-contrast agents: functional assessment of experimental radiation-induced liver injury. J. Magn. Reson. Imaging 10, 52ā56.
Pham, C. D., Roberts, T. P., van Bruggen, N., et al. (1998) Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor. Cancer Invest. 16, 225ā230.
Brasch, R., Pham, C., Shames, D., et al. (1997) Assessing tumor angiogenesis using macromolecular MR imaging contrast media. J. Magn. Reson. Imaging 7, 68ā74.
Aksoy, F. G. and Lev, M. H. (2000) Dynamic contrast-enhanced brain perfusion imaging: technique and clinical applications. Semin. Ultrasound CTMR 21, 462ā477.
Padhani, A. R., Gapinski, C. J., Macvicar, D. A., et al. (2000) Dynamic contrast enhanced MRI of prostate cancer: correlation with morphology and tumour stage, histological grade and PSA. Clin. Radiol. 55, 99ā109.
Kurhanewicz, J., Swanson, M. G., Nelson, S. J., and Vigneron, D. B. (2002) Combined magnetic resonance imaging and spectroscopic imaging approach to molecular imaging of prostate cancer. J. Magn. Reson. Imaging 16, 451ā463.
Mueller-Lisse, U. G., Vigneron, D. B., Hricak, H., et al. (2001) Localized prostate cancer: effect of hormone deprivation therapy measured by using combined three-dimensional 1H MR spectroscopy and MR imaging: clinicopathologic casecontrolled study. Radiology 221, 380ā390.
Males, R. G., Vigneron, D. B., Star-Lack, J., et al. (2000) Clinical application of BASING and spectral/spatial water and lipid suppression pulses for prostate cancer staging and localization by in vivo 3D 1H magnetic resonance spectroscopic imaging. Magn. Reson. Med. 43, 17ā22.
Yu, K. K., Scheidler, J., Hricak, H., et al. (1999) Prostate cancer: prediction of extracapsular extension with endorectal MR imaging and three-dimensional proton MR spectroscopic imaging. Radiology 213, 481ā488.
Scheidler, J., Hricak, H., Vigneron, D. B., et al. (1999) Prostate cancer: localization with three-dimensional proton MR spectroscopic imaging-clinicopathologic study. Radiology 213, 473ā480.
Artemov, D., Pilatus, U., Chu, S., Mori, N., Nelson, J. B., and Bhujwalla, Z. M. (1999) Dynamics of prostate cancer cell invasion studied in vitro by NMR microscopy. Magn. Reson. Med. 42, 277ā282.
Kaji, Y., Kurhanewicz, J., Hricak, H., et al. (1998) Localizing prostate cancer in the presence of postbiopsy changes on MR images: role of proton MR spectroscopic imaging. Radiology 206, 785ā790.
Parivar, F., Hricak, H., Shinohara, K., et al. (1996) Detection of locally recurrent prostate cancer after cryosurgery: evaluation by transrectal ultrasound, magnetic resonance imaging, and three-dimensional proton magnetic resonance spectroscopy. Urology 48, 594ā599.
Kurhanewicz, J., Vigneron, D. B., Hricak, H., et al. (1996) Prostate cancer: metabolic response to cryosurgery as detected with 3D H-1 MR spectroscopic imaging. Radiology 200, 489ā496.
Kurhanewicz, J., Vigneron, D. B., Hricak, H., Narayan, P., Carroll, P., and Nelson, S. J. (1996) Three-dimensional H-1 MR spectroscopic imaging of the in situ human prostate with high (0.24-0.7-cm3) spatial resolution. Radiology 198, 795ā805.
Kurhanewicz, J., Vigneron, D. B., Nelson, S. J., et al. (1995) Citrate as an in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and normal prostate peripheral zone: detection via localized proton spectroscopy. Urology 45, 459ā466.
Blackstock, A. W., Lightfoot, H., Case, L. D., et al. (2001) Tumor uptake and elimination of 2?,2?-difluoro-2?-deoxycytidine (gemcitabine) after deoxycytidine kinase gene transfer: correlation with in vivo tumor response. Clin. Cancer Res. 7, 3263ā3268.
Brix, G., Bellemann, M. E., Gerlach, L., and Haberkorn, U.(1998) Intra-and extracellular fluorouracil uptake: assessment with contrast-enhanced metabolic F-19 MR imaging. Radiology 209, 259ā267.
Vion-Dury, J., Machy, P., Confort-Gouny, S., Leserman, L., and Cozzone, P. J. (1993) Specific in vitro labeling of cells with a fluorine-19 probe encapsulated in antibody-targeted liposomes: a F-19 NMR spectroscopy study. Magn. Reson. Med. 29, 252ā255.
Wolf, W., Albright, M. J., Silver, M. S., Weber, H., Reichardt, U., and Sauer, R. (1987) Fluorine-19 NMR spectroscopic studies of the metabolism of 5-fluorouracil in the liver of patients undergoing chemotherapy. Magn. Reson. Imaging 5, 165ā169.
Yamada, K., Matsuzawa, T., Sato, T., et al. (1986) In vivo F-19 NMR imaging and the influence of oxygenation on relaxation time. Sci. Rep. Res. Inst. Tohoku Univ. [Med.] 33, 44ā48.
Kanazawa, Y., Momozono, Y., Ishikawa, M., et al. (1986) Metabolic pathway of 2-deoxy-2-fluoro-D-glucose studied by F-19 NMR. Life Sci. 39, 737ā742.
Raleigh, J. A., Franko, A. J., Treiber, E. O., Lunt, J. A., and Allen, P. S. (1986) Covalent binding of a fluorinated 2-nitroimidazole to EMT-6 tumors in Balb/C mice: detection by F-19 nuclear magnetic resonance at 2.35 T. Int. J. Radiat. Oncol. Biol. Phys. 12, 1243ā1245.
Nicholson, J. K., Connelly, J., Lindon, J. C., and Holmes, E. (2002) Metabonomics: a platform for studying drug toxicity and gene function. Nat. Rev. Drug Discov. 1, 153ā161.
Mazurchuk, R., Glaves, D., and Raghavan, D. (1997) Magnetic resonance imaging of response to chemotherapy in orthotopic xenografts of human bladder cancer. Clin. Cancer Res. 3, 1635ā1641.
Ostrowitzki, S., Fick, J., Roberts, T. P., et al. (1998) Comparison of gadopentetate dimeglumine and albumin-(Gd-DTPA)30 for microvessel characterization in an intracranial glioma model. J. Magn. Reson. Imaging 8- 799ā806.
Schellenberger, E. A., Bogdanov, A. Jr., Hogemann, D., Tait, J., Weissleder, R., and Josephson, L. (2002) Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Mol. Imaging 1, 102ā107.
Peter Bigler. NMR Spectroscopy: Processing Strategies, 2nd ed., Wiley-VCH, New York, 2000.
de Graaf, RA. In Vivo NMR Spectroscopy, Wiley, New York, 1988.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2005 Humana Press Inc.
About this protocol
Cite this protocol
Mazurchuk, R., Spernyak, J.A. (2005). Magnetic Resonance Imaging of Tumor Response to Chemotherapy. In: Blumenthal, R.D. (eds) Chemosensitivity: Volume II. Methods in Molecular Medicineā¢, vol 111. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-889-7:381
Download citation
DOI: https://doi.org/10.1385/1-59259-889-7:381
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-58829-586-6
Online ISBN: 978-1-59259-889-2
eBook Packages: Springer Protocols