Quantitative ultrasound (QUS) is a promising technique for non-invasive tissue characterization.In this work, the potential of QUS to assess thermal therapy in liver tissue was examined. Specifically, the QUS parameters of attenuation slope, effective scatterer size (ESD), effective acoustic concentration (EAC), and envelope statistics parameters µ and k were evaluated with respect to their ability to discriminate between heated and unheated liver tissue. Two sets of experiments were conducted for this purpose. In the first, a series of freshly excised and bisected rat livers was exposed by placing half of a lobe in a saline bath at 60 °C for 10 minutes and the other half in 37 °C saline. Each sample was then scanned using single-element ultrasonic transducers with a nominal center frequency of 20 MHz. In the second experiment, a series of fresh rat livers was exposed to high-intensity focused ultrasound (HIFU) to produce a discolored region of permanent damage. These samples were scanned in the area of damage before and after HIFU exposure with a 20 MHz single element transducer. Samples in both experiments were preserved, and histology slides were generated.In the saline bath experiments, statistically significant differences in attenuation slope, ESD, and EAC were observed between heated and unheated samples, while the changes in k and µ were not statistically significant. Attenuation slope increased on average from 0.65 dB/cm/MHz in untreated liver to 1.1 dB/cm/MHz in treated liver. Statistically significant differences (p<0.05) in ESD and EAC were observed using spherical Gaussian and fluid-filled sphere models between unheated and heated sides of every sample examined, with ESD decreasing by 34% and EAC increasing by 18 dB with thermal insult.A linear model was also considered, and statistically significant increases in slope were observed for all samples, as well as statistically significant decreases in intercept for 5 of 7 samples. The mean k parameter was found to decrease for 5 of 6 samples, although these changes were not statistically significant. Histology slides revealed a decrease of approximately 2.5% in cell diameter with heating.The HIFU experiments resulted in an increase in ESD and decrease in EAC in the region of the lesion as determined by visual inspection of the sample. The increases in ESD were significant in 3 of 5 samples for both spherical Gaussian and fluid-filled sphere form-factor models, while the decreases in EAC were statistically significant for 4 of 5 samples for these same models. Statistically significant differences were observed in spectral slope in 3 of 5 samples and in spectral intercept in 2 of 5 samples.Envelope statistics parameters were found to be insensitive to changes with HIFU exposure. Histology slides revealed no appreciable change in cell size.iii The results of this work suggest that QUS is capable of assessing HIFU and thermal therapy. ESD and attenuation slope were found to have the most potential to discriminate between unheated and heated liver s...