Fig. 5.

Simplified illustration of key differences in liver fat measurement between histology and PDFF.

In fatty liver disease, lipid droplets accumulate in the cytoplasm of hepatocytes, which represent the principal tissue cell type. However, cells other than hepatocytes comprise approximately one-third of the total hepatic cell population (Fig. 4A). In histological analysis of steatosis, a pathologist visually estimates liver fat as the fraction of macrovesicular lipid droplet-containing hepatocytes (n_HC-LD), out of all visible hepatocytes (n_HC + n_HC-LD) within a histological cross-section. A 100% steatosis is reached when all the visible hepatocytes contain macrovesicular lipid droplets (exemplified on the left). However, liver fat as measured by MRS/MRI-PDFF is calculated by dividing the MR-visible proton density of tissue fat (PD_FAT) by the sum of proton densities of tissue fat and water (PD_FAT + PD_WATER). PDFF takes into account the spectral complexity of fat, including the smaller fat peaks (arrows in yellow) relative to that of water (arrow in blue). In the present study, 100% histological steatosis corresponded to an average PDFF of 33%. A representative MR spectrum from a patient with a PDFF of 33% is shown on the right. In addition to hepatocytes, the tissue volume fraction probed by MRS/MRI contains other cell types as well as components of the extracellular matrix, influencing the MR-visible water-to-fat ratio and presumably contributing to the numerical difference between PDFF and histological steatosis. HC, hepatocyte; LD, lipid droplet; MR, magnetic resonance; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; PD, proton density; PDFF, proton density fat fraction.