Separate calculation of DW-MRI in assessing therapeutic effect in liver tumors in rats

Figure 1 Tumor growth delay. A: Representative axial magnetic resonance images of liver tumors acquired with T2-weighted images (T2WI) [repetition/echo time (TR/TE) = 3860/106 ms], contrast enhanced T1-weighted images (CE-T1WI) (TR/TE = 535/9.2 ms) and HE stained sections. Top row magnetic resonance images: After the combination therapy with ZDTHA, the tumor (solid arrow) in the right liver lobe showed delayed growth with massive central necrotic area (dotted arrow) compared to the control tumor on day 2; Middle row magnetic resonance images: After ZD6126 treatment, the right tumor also showed delayed growth compared to the control tumor on day 2 , however, the tumor necrotic area was reduced (dotted arrow) because the tumor regrew from viable rim; Bottom row magnetic resonance images: In a control animal, the tumor grew remarkably at 2 d; HE sections: The tumor (solid arrow) and central necrotic areas (dotted arrow) in different groups were verified by HE staining; B: The graph indicated that ZDTHA induced a significant tumor volume growth delay during the experiment, compared to both the ZD6126 and control groups (^bP < 0.01 for both; C: The box plots showed significantly higher percentages of necrotic area (necrosis/tumor) on HE stained sections in both the ZDTHA and ZD6126 groups compared to the control group (P = 0.000 for both). No significant difference in necrosis was found between the ZDTHA and ZD6126 groups (P = 0.09).

Figure 2 Apparent diffusion coefficient maps for tumors. A: Representative maps of apparent diffusion coefficient (ADC)_all and ADC_high for liver tumors (solid arrow) in three groups. The area of therapy-induced necrosis (dotted arrow) was significantly larger in the ZDTHA group than those observed in both the ZD6126 and control groups; B: The dynamic change of ADC_all during the experiment (^aP < 0.05, ^bP < 0.01 vs control; respectively); C: The dynamic change of ADC_high during the experiment. Compared to the ADC_all, the increased diffusion due to therapeutic necrosis was better reflected with ADC_high in both the ZDTHA and ZD6126 groups on day 2 (^bP < 0.01 vs control; ^cP < 0.05 vs ZD6126); D: Representative maps of ADC_low and ADC_perf for liver tumors (arrow) in the three groups. The signal intensities observed on ADC_low maps were always higher than those observed on ADC_perf maps at each time point in each group, because ADC_low combines both the perfusion and diffusion effects; E: The dynamic change of ADC_low during the experiment (^aP < 0.05 vs control; ^cP < 0.05 vs ZD6126); F: The dynamic change of ADC_perf during the experiment. Compared to the ADC_low, the perfusion reduction due to the shutdown of tumor vessels was better reflected with ADC_perf in both the ZDTHA and ZD6126 groups at 4 h (^aP < 0.05 vs control). Furthermore, the ADC_perf in the ZDTHA group was even lower compared to the ZD6126 group at 4 h (^cP < 0.05 vs ZD6126).