FIGURE 1.

Magnetic resonance imaging enhanced with MNPs demonstrating the VVF of xenograft tumors in mice with high correlation to histological measures of MVD. A, Three-dimensional volume-rendered image of a control mouse that demonstrates over the right flank, a xenograft tumor with VVF with pseudocolorized 3-dimensional VVF superimposed. B–D, T1-weighted axial MRI images of mice status post xenograft implantation of pancreatic ductal carcinoma in the left thoracic wall. Superimposed over the tumor is a pseudocolorized map of VVF with color bar on the left correlating to VVF within the tumor. C and D, There is decreased vascularity in VVF in those mice treated with cyclopamine and Ab5E1 as compared with control. E–G, In control animals, CD31 staining revealed a rich network of capillaries throughout the tumor. F and G, Antihedgehog treatment resulted in a marked decrease in the MVD revealed by the lack of CD31 staining in cyclopamine- (F) and Ab5E1-treated (G) animals. H, Quantitative analysis using mean VVF also supported the qualitative observations. Mean VVF ± SEM of control tumors are 11.0 ± 0.5 versus 4.0 ± 0.5 for Ab5E1, 4.3 ± 0.6 for forskolin, and 0.7 ± 0.4 for cyclopamine (Table 1). Statistical analysis (ANOVA) demonstrated a statistically significant difference (P < 0.001) among all these groups. I, Least squares linear regression analyses were performed comparing VVF with MVD and demonstrates excellent correlation, R² = 0.85 (P < 0.05).