Quantitative ultrasound (US) imaging for fatty liver disease

Abstract

Hepatic steatosis, which indicates the accumulation of fat in hepatocytes, is common and has a broad disease spectrum according to its pathogenesis and its severity. Clinically, the occurrence of non-alcoholic fatty liver disease (NAFLD), the most common type of hepatic steatosis, is strongly correlated with metabolic disease, and atherosclerotic cardiovascular disease. NAFLD having potential to progress into more advanced stage of fibrosis/cirrhosis has been the most common cause of chronic liver disease in Western counties, and the incidence of NAFLD has been known to be increasing. NAFLD is strongly associated with metabolic syndrome characterized by concomitant existence of obesity, diabetes mellitus, dyslipidemia and hypertension. Therefore, NAFLD can be considered as emerging major health problem. Traditionally, liver biopsy with histopathologic examination has been the gold standard method to diagnose and quantify hepatic steatosis. However, invasive nature with potential complication, small sample volume of biopsy specimen as well as high variability in measurement among the pathologists are major drawbacks of liver biopsy, and therefore, liver biopsy cannot be widely used for the evaluation of NAFLD. US which is widely available noninvasive imaging modality with no need of radiation exposure has been used for the screening of NAFLD for patients at risk, providing fairly good diagnostic accuracy to detect moderate to severe degree hepatic steatosis. However, limited diagnostic performances to detect mild degree hepatic steatosis and subjective nature examination with high intra- and inter-observer variability are major limitations of US. To overcome these limitations, several quantitative method using US images including hepatorenal ratio, ASQ and CAP have been implemented, showing promising results. Recently developed ultrasound based quantification tool for hepatic steatosis is controlled attenuation parameter (CAP) obtained from transient elastography (Fibroscan, Echosens, Paris, France). CAP assesses the degree of ultrasound beam attenuation by the intracellular fat vacuoles at the center frequency of M probe (3.5 MHz), and results are appeared as decibels per meter (dB/m), ranging from 100 to 400 dB/m. Considering NAFLD is usually associated with obesity as a manifestation of metabolic syndrome, failure to obtain CAP values in obese patients could be an important limitation of this technique. Acoustic structure quantification (ASQ) which analyses echo amplitude of ultrasound beam and evaluates changes in variance within region of interests has been introduced in clinical practice, and used for the evaluation of diffuse liver disease. Several initial studies using ASQ reported very promising diagnostic accuracy for assessing hepatic steatosis quantitatively both animal and human studies. A commercially available quantification method, acoustic structure quantification (ASQ), was introduced into clinical practice for the evaluation of diffuse liver disease. The method is based on statistical analysis of the difference between theoretical and real echo amplitude distribution. Theoretical echo amplitude distribution indicates that a speckle pattern in a certain liver region is approximated by a function of a Reyleigh distribution based on the assumption that the speckle pattern is generated only by ultrasonic interference of very small scattering objects that are located closer than the wavelength of US. However, real echo amplitude distribution of normal liver does not fit a Reyleigh distribution mainly because of the presence of small vessel walls. As hepaticsteatosis progresses, the real echo amplitude distribution more likely approaches the theoretical echo amplitude distribution with masking of the small structures, such as small vessel walls. In an animal model of hepatic steatosis, a significant correlation was observed between focal disturbance (FD) ratio, calculated by using ASQ, and either fat droplet area or fat droplet size. In a population of living donors for liver transplantation, acoustic structure quantification (ASQ) provides an excellent quantitative tool for hepatic steatosis, and there is a strong linear correlation (r = -0.87; P