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Invited Commentary

¹ Interventional Radiology Section
² Department of Diagnostic Radiology, Division of Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, Houston, Texas

It has been nearly 3 decades since the dependence of tumors on angiogenesis for growth and metastasis was first described (1). The proliferation of capillary endothelial cells is a multistage process that represents a critical component of tumor neovascularization (2). Various factors are involved in the regulation of tumor angiogenesis at the molecular level. One of the most widely studied is vascular endothelial growth factor, or VEGF. In clinical practice, anti-VEGF therapies have produced survival benefits and are being actively integrated into the armamentarium against many different malignancies (3). It has been postulated that neovascularization may have several indirect effects, in addition to the direct alteration of the vasculature, that augment the effect of chemotherapy (4).

The current reference standard for assessment of tumor-related angiogenesis is the evaluation of microvessel density; however, this method has inherent drawbacks, which include the requirement of a tissue sample and, perhaps most important, the inability to elucidate the functional characteristics of the vasculature (5) or its effects on the local tumor milieu.

Diagnostic imaging continues to rapidly evolve from a strictly anatomic, static modality to a functional, dynamic diagnostic tool. As presented in the article by van Vliet et al (6), MR angiography has the capacity to provide a variety of helpful and essential data about tumor angiogenesis that may have several clinical implications.

MR angiography with a variety of contrast agents (that have low or high molecular weight) can be used to assess tumor vasculature. MR angiography with low-molecular-weight contrast agents is currently part of the routine diagnostic work-up for oncology patients. For example, in patients with renal cell cancer, the multiplanar assessment of anatomic relationships of tumor and vascular structures is essential for treatment planning.

To obtain information about local perfusion, dynamic contrast-enhanced MR imaging may be performed with low- or high-molecular-weight agents, with the type of information gathered depending on the kinetics of the MR contrast agent. Techniques exist that are based on the use of T1-weighted enhancement or T2* magnetic susceptibility effects for monitoring the dynamic profile of contrast enhancement in the tumor as a function of time. Newer techniques, such as parallel MR imaging, offer improved temporal resolution with a reduction in patient motion artifacts. From the contrast kinetics curves, perfusion parameters such as blood flow can be estimated. This method also has been used at computed tomography (CT): So-called functional CT has been proposed for evaluation of angiogenesis through monitoring of the dynamics of iodinated contrast agents (7). The risks of contrast material reaction and the potential biologic hazards associated with radiation exposure are minimal at MR angiography, in contrast to those at functional CT. Since the introduction of higher-field-strength magnets (3.0 T) into clinical practice, the use of MR microscopy to generate higher-resolution images is now possible without a substantial loss in the signal-to-noise ratio (8). This tool can be used not only to evaluate the peritumoral vessels but also to obtain insights into the tumor characteristics.

The MR examination as a tool for one-stop oncologic imaging continues to evolve. Traditionally, MR imaging has been used to depict the anatomy of the tumor, adjacent structures, and the regional vasculature. A combination of methods, such as dynamic contrast-enhanced MR imaging combined with structural MR imaging, has been used to obtain both functional and anatomic information in breast imaging, with dynamic contrast-enhanced MR imaging being used to differentiate benign neoplasms from malignant ones. Changes in perfusion parameters clearly illustrate the interaction of the antiangiogenic therapy with the tumor vasculature and may be used in future clinically to prognosticate the benefits of treatment.

As the field of oncologic imaging evolves, the use of MR for oncologic evaluation will be extended to include the acquisition of functional data such as blood flow and perfusion parameters and of morphologic information about tumor microvasculature in addition to the traditional anatomic information. This further development will help to optimize patient selection and treatment outcomes.

	References

Top References

 

1. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285(21):1182–1186.
2. Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000;21(3):505–515.[Abstract/Free Full Text]
3. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335–2342.[Abstract/Free Full Text]
4. Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004;10(2):145–147.[CrossRef][Medline]
5. Fanelli M, Locopo N, Gattuso D, Gasparini G. Assessment of tumor vascularization: immunohistochemical and non-invasive methods. Int J Biol Markers 1999;14(4):218–231.[Medline]
6. van Vliet M, van Dijke CF, Wielopolski PA, et al. MR angiography of tumor-related vasculature: from the clinic to the microenvironment. RadioGraphics 2005;25(Spec Issue):S85–S98.[Abstract/Free Full Text]
7. Xiong HQ, Herbst R, Faria SC, et al. A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Invest New Drugs 2004;22(4):459–466.[CrossRef][Medline]
8. Maronpot RR, Sills RC, Johnson GA. Applications of magnetic resonance microscopy. Toxicol Pathol 2004;32(suppl 2):42–48.

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