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

Purpose To investigate the physiological origins responsible for the varying blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) responses to carbogen (95% O2/5% CO2) 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 R2* and R2 rates of both tumor types, and indicated a significant four‐fold larger blood volume in the GH3 tumor. The ratio ΔR2*/ΔR2 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 R2* 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 R2* 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. J. Magn. Reson. Imaging 2003;17:445–454. © 2003 Wiley‐Liss, Inc.