Quantitative ultrasound (QUS) techniques are emerging to be useful for assessing nonalcoholic fatty liver disease (NAFLD), the accumulation of fat droplets in the liver without alcohol intake. Several QUS parameters, such as the backscatter coefficient (BSC), are known to be correlated with liver fat content. However, the underlining ultrasonic scattering mechanisms are not fully understood. Understanding these mechanisms may yield better QUS models for improved diagnostics. This study's purpose is to test the following hypothesized mechanism: hepatocyte nuclei are acoustic scattering sites and the accumulation of fat droplets changes the spatial distribution of hepatocyte nuclei, leading to the change of the structure function (SF), a component of the BSC. Hematoxylin and eosin-stained liver histopathological slides from 48 participants were digitized. Hepatocyte nuclei and fat droplets were automatically recognized. For each participant, the SF versus frequency was calculated from the nuclear distribution. The fat fraction (FF) was determined by the fractional surface area of fat droplets. The SF was positively correlated with the FF (Pearson's r ∼ 0.4, p < 10-4) between frequencies 1 and 30 MHz, supporting the hypothesized mechanism. Other potential mechanisms, such as the additional scattering caused by fat droplets, will also be discussed. [Work supported by R01DK106419 and R01CA226528-01A1.]