Estimation of tumor microvessel density by MRI using a blood pool contrast agent

  • Authors:
    • Fuminori Hyodo
    • Gadisetti V.R. Chandramouli
    • Shingo Matsumoto
    • Ken-ichiro Matsumoto
    • James B. Mitchell
    • Murali C. Krishna
    • Jeeva P. Munasinghe
  • View Affiliations

  • Published online on: October 1, 2009     https://doi.org/10.3892/ijo_00000392
  • Pages: 797-804
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Abstract

Recognition of importance of angiogenesis to tumor growth, metastasis, and treatment outcome has led to efforts to develop non-invasive methods for longitudinal monitoring of tumor microvasculature. We describe a steady-state MRI technique to determine absolute blood volume (BV) as a marker of microvascular density with improved spatial and temporal resolution using an ultra small super paramagnetic iron oxide (USPIO). A noise reduction scheme for BV imaging was also proposed based on weighting factors derived by pre-contrast signal level as an adjustable additive constant. Gradient echo sequence was used for BV imaging with MRI at 7T. Optimal imaging conditions (USPIO dose and echo time) were determined by USPIO dose-dependent studies ex vivo and in vivo. Improved analysis strategies were at first applied for cerebral BV estimation in mice, which were found in good agreement with the literature values. These methods were then used to determine tumor BV in mice. The optimal concentration of USPIO for BV estimates was found to range from 3.6 to 4.48 mM (estimated as Fe concentration) in ex vivo experiments corresponding to an in vivo dosage of 215-287 µmol/kg body weight, whereas a USPIO dose of 287 µmol/kg leads to higher cerebral BV estimate in vivo than the reported values. Application of the BV imaging method to evaluation of anti-angiogenic effect of Sunitinib in squamous cell carcinoma (SCC) tumor bearing mice revealed ≈46% reduction in tumor BV 4 days after start of Sunitinib treatment. The results show that the MRI approach using USPIO yields high-resolution absolute BV images and the method can be conveniently applied to monitor longitudinal tumor microvessel density changes as a function of growth or in response to treatment.

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October 2009
Volume 35 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hyodo F, Chandramouli GV, Matsumoto S, Matsumoto K, Mitchell JB, Krishna MC and Munasinghe JP: Estimation of tumor microvessel density by MRI using a blood pool contrast agent. Int J Oncol 35: 797-804, 2009
APA
Hyodo, F., Chandramouli, G.V., Matsumoto, S., Matsumoto, K., Mitchell, J.B., Krishna, M.C., & Munasinghe, J.P. (2009). Estimation of tumor microvessel density by MRI using a blood pool contrast agent. International Journal of Oncology, 35, 797-804. https://doi.org/10.3892/ijo_00000392
MLA
Hyodo, F., Chandramouli, G. V., Matsumoto, S., Matsumoto, K., Mitchell, J. B., Krishna, M. C., Munasinghe, J. P."Estimation of tumor microvessel density by MRI using a blood pool contrast agent". International Journal of Oncology 35.4 (2009): 797-804.
Chicago
Hyodo, F., Chandramouli, G. V., Matsumoto, S., Matsumoto, K., Mitchell, J. B., Krishna, M. C., Munasinghe, J. P."Estimation of tumor microvessel density by MRI using a blood pool contrast agent". International Journal of Oncology 35, no. 4 (2009): 797-804. https://doi.org/10.3892/ijo_00000392