Purpose: Quantitative ultrasound approaches can capture tissue morphologic properties to augment clinical diagnostics. This study aims to clinically assess whether quantitative ultrasound spectroscopy (QUS) parameters measured in hepatocellular carcinoma (HCC) tissues can be differentiated from those measured in at-risk or healthy liver parenchyma.

Methods: This prospective Health Insurance Portability and Accountability Act (HIPAA)–compliant study was approved by the Institutional Review Board. Fifteen patients with HCC, 15 non-HCC patients with chronic liver disease, and 15 healthy volunteers were included (31.1% women; 68.9% men). Ultrasound radiofrequency data were acquired in each patient in both liver lobes at two focal depths (3/9 cm). Region of interests (ROIs) were drawn on HCC and liver parenchyma. The average normalized power spectrum for each ROI was extracted, and a linear regression was fit within the −6 dB bandwidth, from which the midband fit (MBF), spectral intercept (SI), and spectral slope (SS) were extracted. Differences in QUS parameters between the ROIs were tested by a mixed-effects regression.

Results: There was a significant intraindividual difference in MBF, SS, and SI between HCC and adjacent liver parenchyma (P < 0.001), and a significant interindividual difference between HCC and at-risk and healthy non-HCC parenchyma (P < 0.001). In patients with HCC, cirrhosis (n = 13) did not significantly change any of the three parameters (P > 0.8) in differentiating HCC from non-HCC parenchyma. MBF (P = 0.12), SI (P = 0.33), and SS (P = 0.57) were not significantly different in non-HCC tissue among the groups.

Conclusions: The QUS parameters are significantly different in HCC versus non-HCC liver parenchyma, independent of underlying cirrhosis. This could be leveraged for improved HCC detection with ultrasound in the future.