Comparing QUS parameters to structural and functional changes in tumors during therapy

Tumor microstructure can potentially be evaluated with quantitative ultrasound (QUS) during therapy, but parameters are influenced by a complex combination of components and modifications in the tumor. To better understand how QUS parameters reflect tumor response to therapy, we estimated effective scatterer diameter (ESD, μm) and effective acoustic concentration (EAC, dB/cm) from ultrasound backscatter measurements in a murine Lewis Lung Carcinoma model on days 7 to 13 after the start of therapy by administration of: anti-angiogenic (AA) agent to inhibit new blood vessels (n = 21); a cytotoxic agent (CA) to damage tumor cells (n = 24) and placebo (n = 24). At D7, there was no significant difference between ESD and EAC for the different therapy groups. At D13, the AA group had higher mean ESD than for CA and placebo (p < 0.005). At D13, the placebo group exhibited a significantly higher EAC compared to the AA (p < 0.005) and was elevated compared to the CA group. Histology showed higher (p < 0.05) necrosis and fibrosis in the AA group at D13 as compared to other groups but no significant differences at D7. Higher mean ESD and lower EAC in the AA group at D13 are consistent with thicker, more sparsely distributed fibrotic structures in the corresponding histology.