Subscribe to RSS
DOI: 10.1055/s-0037-1613539
Magnetic resonance imaging of tumor vasculature
Financial support: Supported by a National Institutes of Health Grant No. CA42238; Sir David Alliance, CBE; the Susan G. Komen Breast Cancer Foundation, USA; the Israel Science Foundation; and the Washington Square Health Foundation, USA.Publication History
Received
04 November 2002
Accepted
05 November 2002
Publication Date:
09 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200301/lookinside/thumbnails/10-1055s-0037-1613539-1.jpg)
Summary
Angiogenic activity and formation of a vascular network facilitate tumor perfusion and play a critical role in tumor growth and metastasis. Tumor vasculature may be visualized by means of parametric imaging of specific morphological and physiological characteristics that collectively describe its properties. In this review, we describe advanced magnetic resonance imaging (MRI) techniques that have been developed in order to image and quantify the distribution of tumor vasculature throughout the tumor and characterize its function. These techniques have been used to monitor changes in the magnetic resonance signal intensity of tissue water hydrogens generated by intrinsic effects, as well as by exogenous contrast agents administered into the blood circulation. We further describe specific applications of magnetic resonance imaging using a contrast agent, gadolinium diethylene triamine penta-acetic acid (GdDTPA), which has long been approved for clinical use. Examples include studies of the vascular properties of breast cancer tumors and metastases in animal models, as well as of breast cancer vasculature in patients. We also discuss the use of MRI to improve breast cancer diagnosis in humans by quantifying the permeability of the tumor vasculature. By maximizing the spatial resolution of the images in both animal and human studies, the capacity of magnetic resonance imaging to enhance our understanding of the processes regulating tumor angio-genesis, and improve the diagnosis of cancer, could be clearly demonstrated.
-
References
- 1 Folkman J. Tumor Angiogenesis. Adv Cancer Res 1985; 43: 175-203.
- 2 Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407: 249-57.
- 3 Los M, Voest EE. The potential role of antivascular therapy in the adjuvant and neoadjuvant treatment of cancer. Semin Oncol 2001; 28: 93-105.
- 4 Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature 2000; 407: 242-8.
- 5 Baish JW, Jain RK. Fractals and cancer. Cancer Res 2000; 60: 3683-8.
- 6 Daniel TO, Abrahamson D. Endothelial signal integration in vascular assembly. Annu Rev Physiol 2000; 62: 649-71.
- 7 Tosetti F, Ferrari N, Flora SD, Albini A. Angioprevention: angiogenesis is a common and key target for cancer chemopreventive agents. FEBS 2002; 16: 2-14.
- 8 Jain RK. Transport of molecules, particles, and cells in solid tumors. Annual Rev Biomed Eng 1999; 1: 241-63.
- 9 Weidner N, Folkman J.. Tumoral vadscularity as a prognostic factor in cancer. In:. Vita VTD, Hellman S, Rosenberg SA. eds. Important advanves in oncology Philadelphia: Lippincott-Raven; 1996: 167-190 vol. 11.
- 10 Ahlgren J, Risberg B, Villman K, Bergh J. Angiogenesis in invasive breast carcinoma – a prospective study of tumour heterogeneity. Eur J Cancer 2002; 38: 64-9.
- 11 Foster FS, Burns PN, Simpson DH, Wilson SR, Christopher DA, Goertz DE. Ultrasound for the visualization and quantification of tumor microcirculation. Cancer Matastasis Rev 2000; 19: 131-8.
- 12 Anderson H, Price P. Clinical measurement of blood flow in tumours using positron emission tomography: a review. Nucl Med Commun 2002; 23: 131-8.
- 13 Gillies RJ, Bhujawalla ZM, Evelhoch J. et al. Applications of magnetic resonance in model systems: tumor biology and physiology. Neoplasia 2000; 2: 139-51.
- 14 Padhani AR. Dynamic contrast-enhanced MRI in clinical oncology. J Magn Reson Imaging 2002; 16: 407-22.
- 15 Brown EB, Campbell RB, Tsuzuki Y. et al. In vivo measurement of gene expression, angio-genesis and physiological function in tumors using multiphoton laser scanning microscopy. Nature Med 2001; 7: 864-8.
- 16 Gillies RJ. NMR in Physiology and Biomedicine. Academic Press; 1994
- 17 Robinson SP, Rodrigues LM, Ojugo AS, Mc-Sheehy PM, Howe FA, Griffiths JR. The response to carbogen breathing in experimental tumour models monitored by gradient-recalled echo magnetic resonance imaging. Br J Cancer 1997; 75: 1000-6.
- 18 Robinson SP, Howe FA, Rodrigues LM, Stubbs M, Griffiths JR. Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow. Semin Radiat Oncol 1998; 8: 197-207.
- 19 Al-Hallaq HA, River JN, Zamora M, Oikawa H, Karczmar GS. Correlation of magnetic resonance and oxygen microelectrode measurements of carbogen-induced changes in tumor oxygenation. Int J Radiat Oncol Biol Phys 1998; 41: 151-9.
- 20 Al-Hallaq HA, Fan X, Zamora M, River JN, Moulder JE, Karczmar GS. Spectrally inhomogeneous BOLD contrast changes detected in rodent tumors with high spectral and spatial resolution MRI. Nmr Biomed 2002; 15: 28-36.
- 21 Abramovitch R, Frenkiel D, Neeman M. Analysis of subcutaneous angiogenesis by gradient echo magnetic resonance imaging. Magn Reson Med 1998; 39: 813-24.
- 22 Neeman M, Dafni H, Bukhari O, Braun RD, Dewhirst MW. In vivo BOLD contrast MRI mapping of subcutaneous vascular function and maturation: validation by intravital microscopy. Magn Reson Med 2001; 45: 887-98.
- 23 Williams DS, Detre JA, Leigh JS, Koretsky AP. Magnetic resonance imaging of perfusion using spin inversion of arterial water. Proc Natl Acad Sci USA 1992; 89: 212-6.
- 24 Silva AC, Kim SG, Garwood M. Imaging blood flow in brain tumors using arterial spin labeling. Magn Reson Med 2000; 44: 169-73.
- 25 Le Bihan D, Turner R. The capillary network: a link between IVIM and classical perfusion. Magn Reson Med 1992; 27: 171-8.
- 26 Wang Z, Su MY, Najafi A, Nalcioglu O. Effect of vasodilator hydralazine on tumor microvascular random flow and blood volume as measured by intravoxel incoherent motion (IVIM) weighted MRI in conjunction with Gd-DTPA-Albumin enhanced MRI. Magn Reson Imaging 2001; 19: 1063-72.
- 27 Furman-Haran E, Margalit R, Grobgeld D, Degani H. High resolution MRI of MCF7 human breast tumors: complemented use of iron oxide microspheres and Gd-DTPA. J Magn Reson Imaging 1998; 8: 634-41.
- 28 Wang YX, Hussain SM, Krestin GP. Super-paramagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 2001; 11: 2319-31.
- 29 Bhujwalla ZM, Artemov D, Natarajan K, Ackerstaff E, Solaiyappan M. Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts. Neoplasia 2001; 3: 143-53.
- 30 Aime S, Cabella C, Colombatto S, Geninatti Crich S, Gianolio E, Maggioni F. Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations. J Magn Reson Imaging 2002; 16: 394-406.
- 31 Brasch R, Turetschek K. MRI characterization of tumors and grading angiogenesis using macromolecular contrast media: status report. Eur J Radiol 2000; 34: 148-55.
- 32 Turetschek K, Huber S, Floyd E. et al. MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation. Radiology 2001; 218: 562-9.
- 33 Roberts TP. Physiologic measurements by contrast-enhanced MR imaging: expectations and limitations. J Magn Reson Imaging 1997; 7: 82-90.
- 34 Ackerman JJ, Ewy CS, Becker NN, Shalwitz RA. Deuterium nuclear magnetic resonance measurements of blood flow and tissue perfusion employing 2 H2O as a freely diffusible tracer. Proc Natl Acad Sci USA 1987; 84: 4099-102.
- 35 Simpson NE, He Z, Evelhoch JL. Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods. Magn Reson Med 1999; 42: 42-52.
- 36 Bogin L, Margalit R, Ristau H, Mispelter J, Degani H. Parametric imaging of tumor perfusion with deuterium magnetic resonance imaging. Microvasc Res 2002; 64 (01) 104-15.
- 37 Su MY, Wang Z, Carpenter PM, Lao X, Muhler A, Nalcioglu O. Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents. J Magn Reson Imaging 1999; 9: 177-86.
- 38 Henderson E, Sykes J, Drost D, Weinmann HJ, Rutt BK, Lee TY. Simultaneous MRI measurement of blood flow, blood volume, and capillary permeability in mammary tumors using two different contrast agents. J Magn Reson Imaging 2000; 12: 991-1003.
- 39 Turner R, Howseman A, Rees GE, Josephs O, Friston K. Functional magnetic resonance imaging of the human brain: data acquisition and analysis. Exp Brain Res 1998; 123: 5-12.
- 40 Bosmans H, Wilms G, Dymarkowski S, Marchal G. Basic principles of MRA. Eur J Radiol 2001; 38: 2-9.
- 41 Furman-Haran E, Degani H. Parametric analysis of breast MRI. J Comput Assist Tomogr 2002; 26: 376-86.
- 42 Padhani AR, Gapinski CJ, Macvicar DA. et al. Dynamic Contrast Enhanced MRI of Prostate Cancer: Correlation with Morphology and Tumour Stage, Histological Grade and PSA. lin Radiol 2000; 55: 99-109.
- 43 Knopp MV, Weiss E, Sinn HP. et al. Patho-physiologic basis of contrast enhanced breast tumors. JMRI 1999; 10: 260-6.
- 44 Knopp MV, Giesel FL, Marcos H, von Tengg-Kobligk H, Choyke P. Dynamic contrast-enhanced magnetic resonance imaging in oncology. Top Magn Reson Imaging 2001; 12: 301-8.
- 45 Larsson HBW, Stubgaard M, Frederiksen JL, Jensen M, Henriksen O, Paulson OB. Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors. Magn Reson Med 1990; 16: 117-31.
- 46 Brix G, Semmler W, Port R, Schad LR, Layer G, Lorenz WJ. Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr 1991; 15: 621-8.
- 47 Tofts PS, Kermode AG. Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 1991; 17: 357-67.
- 48 Kety SS. The theory and applications of the exchange of inert gas at the lungs and tissues. Pharmacol Rev 1951; 3: 1-41.
- 49 Patlak CS, Fenstermacher JD, Blasberg RG. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983; 3: 1-7.
- 50 Tofts PS. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging 1997; 7: 91-101.
- 51 Parker GJ, Tofts PS. Pharmacokinetic analysis of neoplasms using contrast-enhanced dynamic magnetic resonance imaging. Top Magn Reson Imaging 1999; 10: 130-42.
- 52 Furman-Haran E, Margalit R, Grobgeld D, Degani H. Dynamic contrast-enhanced magnetic resonance imaging reveals stress-in-duced angiogenesis in MCF7 human breast tumors. Proc Natl Acad Science 1996; 93: 6247-51.
- 53 Furman-Haran E, Grobgeld D, Degani H. Dynamic contrast-enhanced imaging and analysis at high spatial resolution of MCF7 human breast tumors. J Magn Reson 1997; 128: 161-71.
- 54 Furman E, Margalit R, Bendel P, Horowitz A, Degani H. In vivo studies by magnetic resonance imaging and spectroscopy of the response to tamoxifen of MCF7 human breast cancer implanted in nude mice. Cancer Commun 1991; 3: 287-97.
- 55 Haran EF, Maretzek AF, Goldberg I, Horowitz A, Degani H. Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth. Cancer Res 1994; 54: 5511-4.
- 56 Bogin L, Degani H. Hormonal regulation of VEGF in orthotopic MCF7 human breast cancer. Cancer Res 2002; 62: 1948-51.
- 57 Bogin L, Margalit R, Mispelter J, Degani H. Parametric imaging of tumor perfusion using flow- and permeability-limited tracers. J Magn Reson Imaging 2002; 16: 289-99.
- 58 Heywang SH, Hahn D, Schmidt H. et al. MR imaging of the breast using gadolinium-DTPA. J Comput Assist Tomogr 1986; 10: 199-204.
- 59 Kaiser WA, Zeitler E. MR imaging of the breast: fast imaging sequences with and without Gd-DTPA. Preliminary observations. Radiology 1989; 170: 681-6.
- 60 Degani H, Gusis V, Weinstein D, Fields S, Strano S. Mapping pathophysiological features of breast tumors by MRI at high spatial resolution. Nature Med 1997; 3: 780-2.
- 61 Weinstein D, Strano S, Cohen P, Fields S, Gomori JM, Degani H. Breast fibroadenoma: mapping of pathophysiologic features with three-time-point, contrast-enhanced MR imaging – pilot study. Radiology 1999; 210: 233-40.
- 62 Furman-Haran E, Grobgeld D, Kelcz F, Degani H. Critical role of spatial resolution in dynamic contrast-enhanced breast MRI. J Magn Reson Imaging 2001; 13: 862-7.
- 63 Kelcz F, Furman-Haran E, Grobgeld D, Degani H. Clinical Testing of high-spatial-resolution parametric contrast-enhanced MR Imaging of the breast. Am J Roentgenol. 2002 In press, December.