0427 and P=0.0050, respectively). Accordingly, the mean relative tumor necrosis volume visualized on CE-T1WIs in the ZdTha group was significantly larger compared to that of the Zd group at 6 d and 12 d after treatment (P=0.0026 and P=0.0140, selleck screening library respectively) (Fig. S1). ADC maps At 4 h: Compared to controls, both the ZdTha and Zd groups showed a significant drop in the rADC (P<0.0001 for both), due to the vascular shutdown induced by Zd. No significant difference of rADC was seen between the Tha group and controls (P=0.181). At 2 d: The Zd-induced tumor necrosis caused a rise in the rADCs of both ZdTha and Zd groups. However, the increases were significantly greater than the rADCs of controls only in the ZdTha group (P=0.0003), not in the Zd group (P=0.0751).

In addition, the rADC was much higher in the ZdTha than in the Zd group (P=0.0256). In contrast, the rADC in the Tha group was significantly reduced compared to controls (P=0.0003). At 6 d: Only the rADC of the ZdTha group was significantly higher (P=0.0386) than that of the controls; the rADCs in the Zd and Tha groups were not significantly different compared to controls (P=0.1229, P=0.0858, respectively). However, a sharp increase in rADC was observed in the Tha group compared to that observed at 2 d. At 12 d: Due to the regrowth of tumors, the rADCs in the ZdTha and Zd groups began to decrease from 6 d to 12 d. However, the rADC remained unchanged in the Tha group. Consequently, the rADCs in the ZdTha and Tha groups were much higher than those observed in both the Zd group (P=0.0251, P=0.0026, respectively) and the control group (P=0.

0190, P=0.0160, respectively) (Fig. 3, Table S2). Figure 3 ZdTha increased the tumor ADC value, apoptosis, and necrosis. HE staining Twelve days after treatment, the percentages of necrotic compared to total tumor areas on HE stained tumor sections were significantly higher in both ZdTha and Tha groups compared to the control group (P=0.0019 and P=0.0054, respectively). In contrast, no significant difference was found in the necrotic areas of the Zd and control groups (P=0.0727) (Fig. 4A). Figure 4 Tumor necrosis and apoptosis at 12 d after treatment. Apoptosis on IHC stained slices Similar to findings with HE staining, the percentages of apoptotic areas compared to total tumor areas on IHC stained tumor sections were significantly higher in both ZdTha and Tha groups compared to the control group (P=0.

0004 and P=0.0011, respectively). In contrast, no significant difference was found in the apoptotic areas of the Zd and control groups (P=0.0543) at 12 d after treatment (Fig. 4B). ZdTha Prolonged the Reduction of Tumor Hemodynamic Indexes Compared to the controls, tumor rBV decreased dramatically at 4 h, presumably due to a rapid Batimastat vascular shutdown induced by Zd in both the Zd and ZdTha groups (both P<0.0001).