Quantitative Imaging Biomarkers of NAFLD

Abstract

Conventional imaging modalities, including ultrasonography (US), computed tomography (CT), and magnetic resonance (MR), play an important role in the diagnosis and management of patients with nonalcoholic fatty liver disease (NAFLD) by allowing noninvasive diagnosis of hepatic steatosis. However, conventional imaging modalities are limited as biomarkers of NAFLD for various reasons. Multi-parametric quantitative MRI techniques overcome many of the shortcomings of conventional imaging and allow comprehensive and objective evaluation of NAFLD. MRI can provide unconfounded biomarkers of hepatic fat, iron, and fibrosis in a single examination-a virtual biopsy has become a clinical reality. In this article, we will review the utility and limitation of conventional US, CT, and MR imaging for the diagnosis NAFLD. Recent advances in imaging biomarkers of NAFLD are also discussed with an emphasis in multi-parametric quantitative MRI.

Keywords: Imaging biomarker; Magnetic resonance imaging; Nonalcoholic fatty liver disease; Proton density fat fraction; Steatosis.

Figures

Fig. 1

Ultrasound of NAFLD—examples. Longitudinal ultrasound images of the right haptic lobe and right kidney (a–d) and transverse images at hepatic venous confluence (e–h) in four patients are shown. In normal liver, the liver parenchyma is slightly more echogenic (i.e., brighter) than the right kidney (a). Posterior structures are well seen, including diaphragm (e). In the steatotic liver, the parenchyma becomes increasingly more echogenic than the kidney (b–d) and deep structures, including the diaphragm (arrow), which become progressively blurred (f–h)

Fig. 2

CT of NAFLD—examples. Axial CT images of the liver in four patients at the level of spleen are shown. In normal liver, the parenchyma is approximately 60 ± 10 Hounsfield unit (HU) in CT density and appears brighter than the spleen and the blood vessels (arrow). As liver becomes steatotic, the CT density of the liver becomes closer to that of fat (approx. −90 HU). In mild steatosis, the liver may be isodense to the spleen and the blood (b). In moderate and severe steatosis, the parenchyma is less dense than the spleen and blood. Typical area of fat sparing is often seen in the periportal regions (c, d), near the gallbladder fossa and adjacent to the fissure for the ligamentum teres

Fig. 3

T1-weighted in- and opposed-phase MRI of NAFLD—examples. Axial in-phase (IP) and opposed-phase (OP) T1-weighted MR images of the liver in four patients are shown. In normal liver (a, e), the liver is brighter than spleen on both T1-weighted IP–OP images. The liver signal on the IP image is similar or slightly higher in signal than the OP image (due to the earlier echo time of OP imaging). In steatotic liver, the signal of triglycerides opposes (i.e., cancels) the liver’s water signal, causing net signal reduction (darker) on the OP images. The differences in the liver signal between the IP and OP images correlate to the severity of steatosis. Arrows blood vessels, s spleen

Fig. 4

MRI PDFF mapping in NAFLD—examples. Axial PDFF images of the liver in four patients generated using Philips mDixon-Quant pulse sequence at 3 T. Average PDFF values of the right lobe are displayed. In normal liver (a), PDFF values are<6 % everywhere in the liver. In steatotic livers (b–d), the liver’s PDFF values increase diffusely and predict borderline–mild (b), mild (c), and moderate (d) steatosis grade at histology

Fig. 5

Simultaneous liver fat and iron quantification—examples. Simultaneous liver fat and iron quantification. A 24-year-old male patient with elevated transaminase, clinically suspected NAFLD (a, d) demonstrating normal liver FF and R2* values [and corresponding liver iron concentration (LIC) of 0.04 mg Fe/g] using Siemens VIBE q-Dixon pulse sequence. A 44-year-old female, also with elevated liver enzymes and obesity (b, e), demonstrating elevated liver FF but normal R2* (LIC = 0.13 mg Fe/g) using GE IDEAL IQ pulse sequence, consistent with moderate steatosis without iron overload. A 58-year-old male with elevated ferritin, diabetes, and obesity (c, f) demonstrating abnormal liver FF and R2* values (LIC = 3.9 mg Fe/g) using Philips mDixon-Quant sequence, compatible with mild–moderate steatosis and mild iron overload. R2*-LIC calibration based on Wood et al. [88]