Associations between histologic features of nonalcoholic fatty liver disease (NAFLD) and quantitative diffusion‐weighted MRI measurements in adults

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common metabolic disorder in adults and children in developed countries (1–3). It is defined by the deposition of lipids within hepatocytes in the absence of substantial alcohol intake. Approximately 20% of patients with NAFLD have a progressive form of the condition known as nonalcoholic steatohepatitis (NASH), which is characterized by the presence of inflammation and hepatocellular injury in addition to steatosis. Patients with NASH may develop fibrosis and can progress to cirrhosis (1). NAFLD is now among the most common causes of cirrhosis in the United States and Europe (3). Clinical management and future therapeutic investigations may benefit from a wider array of tools for quantitative evaluation of the fatty liver disease spectrum. Currently, histology and imaging are both used for evaluating NAFLD (4). In the NASH Clinical Research Network (CRN) Scoring System, liver biopsy specimens are scored for multiple histologic features including steatosis, inflammation, hepatocellular ballooning, and fibrosis (5). The diagnosis of NASH requires a specific pattern of histologic abnormalities that includes, in addition to steatosis, inflammatory cellular infiltrates and hepatocellular ballooning centered around the lobular central vein, with or without fibrosis (6,7). Since liver biopsy is an invasive procedure that samples only a small part of the liver, noninvasive imaging methods are under investigation to fill roles that are complementary or surrogate to histology (4,7). Diffusion-weighted imaging (DWI) is an magnetic resonance imaging (MRI) method under investigation in liver disease. It is sensitive to the microscopic motion of spins as they diffuse and perfuse through tissue (8). Diffusion and perfusion are affected by several tissue characteristics, including the presence of restrictive barriers within tissue, the viscosity of the fluid in which the spins are diffusing, and the velocity and fractional volume of perfusing spins. These tissue characteristics may be altered in chronic liver diseases such as NAFLD, and several recent animal and human studies have reported that steatosis (9–15), inflammation (9,10,16), and fibrosis (16–19) may affect DWI measurements. However, these prior studies appear not to have examined the independent effects of the various histologic features of NAFLD on DWI measurements (ie, with multiple linear regression) in human subjects to determine whether the observed effects are confounded by or attributable to other histologic features. Also, we sought to investigate the effects of inflammation in NAFLD in human subjects. Furthermore, knowledge of the physics and artifacts of liver DWI has progressed since these prior studies. More detailed models of intravoxel incoherent motion (IVIM) have superseded the apparent diffusion coefficient (ADC) for DWI quantification (20,21), and methods to mitigate the bulk motion artifacts that are prominent in liver have been developed (22,23). The purpose of this study was to evaluate the associations between histologic features of NAFLD and quantitative DWI parameters in a cross-sectional clinical study in adults, incorporating recent advances in DWI methodology.