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Volumetric computed tomography (VCT): a new technology for noninvasive, high-resolution monitoring of tumor angiogenesis

Abstract

Volumetric computed tomography (VCT) is a technology in which area detectors are used for imaging large volumes of a subject with isotropic imaging resolution. We are experimenting with a prototype VCT scanner that uses flat-panel X-ray detectors and is designed for high-resolution three-dimensional (3D) imaging. Using this technique, we have demonstrated microangiography of xeno-transplanted skin squamous cell carcinomas in nude mice. VCT shows the vessel architecture of tumors and animals with greater detail and plasticity than has previously been achieved, and is superior to contrast-enhanced magnetic resonance (MR) angiography. VCT and MR images correlate well for larger tumor vessels, which are tracked from their origin on 3D reconstructions of VCT images. When compared with histology, small tumor vessels with a diameter as small as 50 μm were clearly visualized. Furthermore, imaging small vessel networks inside the tumor tissue improved discrimination of vital and necrotic regions. Thus, VCT substantially improves imaging of vascularization in tumors and offers a promising tool for preclinical studies of tumor angiogenesis and antiangiogenic therapies.

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Figure 1: Maximum intensity projections (MIP).
Figure 2: Three-dimensional visualization showing VCT angiography of a tumor-bearing nude mouse, and detailed image of the tumor after magnification (top right).
Figure 3: Visualization of the same subcutaneous squamous cell carcinoma based on VCT and MR angiography.
Figure 4: Comparison of an immunofluorescence image of a subcutaneous squamous cell carcinoma.
Figure 5: Three-dimensional reconstructions of a nude mouse with a subcutaneous squamous cell carcinoma are shown during follow-up with two different imaging windows.

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Acknowledgements

We acknowledge colleagues at GE Global Research for developing the VCT research prototype, especially W. Ross, S. Basu and P. FitzGerald for providing algorithm and technical support. Special thanks to P. Edic and P. FitzGerald (GE Global Research) for careful review of the manuscript. Furthermore, we thank B. Misselwitz and J. Meding from Schering AG (Berlin, Germany) for providing us the MR contrast agent and the careful proofreading of the manuscript.

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Correspondence to Fabian Kiessling.

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Kiessling, F., Greschus, S., Lichy, M. et al. Volumetric computed tomography (VCT): a new technology for noninvasive, high-resolution monitoring of tumor angiogenesis. Nat Med 10, 1133–1138 (2004). https://doi.org/10.1038/nm1101

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