Tumor vascular architecture and function evaluated by non-invasive susceptibility MRI methods and immunohistochemistry

J Magn Reson Imaging. 2003 Apr;17(4):445-54. doi: 10.1002/jmri.10274.

Abstract

Purpose: To investigate the physiological origins responsible for the varying blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) responses to carbogen (95% O(2)/5% CO(2)) breathing observed with different tumor types.

Materials and methods: Susceptibility contrast-enhanced MRI using the exogenous blood pool contrast agent NC100150 to determine blood volume and vessel size, and immunohistochemical-derived morphometric parameters, were determined in GH3 prolactinomas and RIF-1 fibrosarcomas, both grown in mice, which exhibited very different BOLD responses to carbogen.

Results: Administration of NC100150 increased the R(2)* and R(2) rates of both tumor types, and indicated a significant four-fold larger blood volume in the GH3 tumor. The ratio deltaR(2)*/deltaR(2) showed that the capillaries in the GH3 were two-fold larger than those in the RIF-1, in agreement with morphometric analysis. Carbogen breathing induced a significant 25% decrease in R(2)* in the GH3 prolactinoma, whereas the response in the RIF-1 fibrosarcoma was negligible.

Conclusion: Low blood volume and small vessel size (and hence reduced hematocrit) are two reasons for the lack of R(2)* change in the RIF-1 with carbogen breathing. BOLD MRI is sensitive to erythrocyte-perfused vessels, whereas exogenous contrast agents interrogate the total perfused vascular volume. BOLD MRI, coupled with a carbogen challenge, provides information on functional, hemodynamic tumor vasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Dioxide / metabolism*
  • Carcinoma, Hepatocellular / metabolism
  • Dextrans
  • Female
  • Ferrosoferric Oxide
  • Fibrosarcoma / metabolism
  • Immunohistochemistry
  • Iron
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles
  • Mammary Neoplasms, Animal / metabolism
  • Mice
  • Neoplasms / metabolism*
  • Oxides
  • Oxygen / metabolism*
  • Prolactinoma / metabolism

Substances

  • Dextrans
  • Magnetite Nanoparticles
  • Oxides
  • ferumoxtran-10
  • Carbon Dioxide
  • Iron
  • Oxygen
  • Ferrosoferric Oxide