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% 02/5% 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 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.