A review of micro- and macrovascular analyses in the assessment of tumor-associated vasculature as visualized by MR

doi:10.1016/j.neuroimage.2007.03.067

NeuroImage

Volume 37, Supplement 1, 2007, Pages S116-S119

https://doi.org/10.1016/j.neuroimage.2007.03.067 Get rights and content

Abstract

There is currently no noninvasive, reliable method of assessing brain tumor malignancy or of monitoring tumor treatment response. Monitoring changes to tumor vasculature might provide an effective means of assessing both tumor aggressiveness and treatment efficacy. To date, most such research has concentrated upon tumor “microvascular” imaging, with permeability and/or perfusion imaging used to assess vessel changes at the subvoxel level. An alternative approach assesses tumor vasculature at the “macroscopic” level, calculating the numbers and shapes of the larger vessels discriminable by magnetic resonance angiography. This paper provides an overview of magnetic resonance (MR) vascular imaging at both the microscopic (dynamic MR perfusion and permeability) and macroscopic (MR angiographic) levels. The two approaches provide different, complementary information and together could provide important insights into cancer growth as well as new methods of assessing malignancy and tumor treatment response.

Introduction

There is clinical need for a reliable, noninvasive method of assessing brain tumor malignancy and of evaluating treatment response. The American Cancer Society estimates that in 2006 approximately 19,000 new brain tumors will be diagnosed in the US (ACS, 2006). Many thousands of additional patients exhibit abnormalities of unknown significance on screening magnetic resonance (MR) studies. Malignant disease should usually be treated aggressively, whereas benign disease is often treated by watchful waiting. There is currently no effective, clinically accepted, noninvasive method of separating benign from malignant disease.

An even more difficult problem is posed by treatment monitoring. Effective therapy should usually be continued as long as it remains effective, but once it begins to fail it should be changed rapidly. The current standard of practice is to estimate tumor volumes from sequential sets of gadolinium-enhanced, T1 images (Dempsey et al., 2005). Such assessments depend upon comparison of current to past tumor volumes, do not directly evaluate what the tumor will do next and are readily confounded by the necrosis that may appear with successful treatment, since necrosis can induce enhancement and edema indistinguishable from that of tumor growth.

A reliable method of assessing tumor metabolic or physiologic activity noninvasively would be of high value. MR spectroscopy and positron emission tomography are two imaging methods under investigation by several groups. Another promising approach is to assess tumor-associated vasculature. The large majority of such research has concentrated upon the microvasculature. Recently, several papers have proposed analyzing vessel morphology at the “macroscopic” level, using vessels segmented from magnetic resonance angiograms (MRA). The purpose of this report is to review MR imaging of tumor-associated vasculature at both the microscopic and the macroscopic levels.

Section snippets

Background information

Tumor growth beyond minimal size is dependent upon angiogenesis, the process of new blood vessel formation from existing vessels (Folkman, 1971). Vessels are recruited via the expression of agents such as vascular endothelial growth factor (VEGF) and other growth factors (Ferrara et al., 1996, McDonald and Baluk, 2002). Although malignant tumors tend to be more vascular than benign lesions, some benign tumors may be more vascular than many cancers. Moreover, different regions of the same tumor

Microscopic imaging: dynamic perfusion and permeability

The goals of dynamic MR perfusion and permeability imaging are to assess regional cerebral blood flow, volume and permeability via sequential image acquisitions during contrast injection. Changes in intensity values are compared over time within a single voxel or cluster of voxels following injection of contrast. The choice of contrast agent may be gadolinium or a larger molecule that leaks into the extravascular space under conditions of high permeability but not otherwise. Fig. 2 illustrates

Macroscopic imaging: vessel shape analysis from MRA

A different approach to the analysis of tumor-associated vasculature is via a quantitative, statistical measure of vessel shape provided by the vessels segmented from time-of-flight, nonenhanced MRA. Much less is known about the relative disadvantages and advantages of this method both because it is relatively new and because work has been done predominantly by only one group. A disadvantage of this approach is that it inherently cannot analyze vessels of diameter less than the voxel size used

Discussion

The microscopic and macroscopic imaging methods outlined above have different advantages and disadvantages. Microscopic vessel analysis has the advantage of including tiny vessels at subvoxel resolution. However, large and small vessels are considered together, the approach may be sensitive to acute changes in the environment and individual vessels cannot be followed over time. Conversely, macroscopic vessel analysis can follow individual vessels over time and is likely to be less susceptible

Acknowledgment

This work was supported by R01 EB000219 NIH-NIBIB.

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A review of micro- and macrovascular analyses in the assessment of tumor-associated vasculature as visualized by MR

Abstract

Introduction

Section snippets

Background information

Microscopic imaging: dynamic perfusion and permeability

Macroscopic imaging: vessel shape analysis from MRA

Discussion

Acknowledgment

Neuroimaging Clin. N. Am.

Acad. Radiol.

Cancer Facts and Figures 2006

Fractals and cancer

Cancer Res.

Abnormal vessel tortuosity as a marker of treatment response of malignant gliomas: preliminary report

Technol. Cancer Res. Treat.

Malignancy-associated vessel tortuosity: a computer-assisted, MRA study of choroid plexus carcinoma in genetically engineered mice

AJNR

Dynamic magnetic resonance perfusion imaging of brain tumors

Oncologist

Measurement of tumor “size” in recurrent malignant glioma: 1D, 2D or 3D?

AJNR

Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene

Nature

Tumor angiogenesis: therapeutic implications

N. Engl. J. Med.

Dynamic imaging of intracranial lesions using fast spin echo imaging: differentiation of brain tumors and treatment effects

J. Magn. Reson. Imaging