A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease

Abstract

Objective: The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD).

Subjects and methods: In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed.

Results: CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all).

Conclusion: Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD.

Keywords: attenuation; backscatter; grading accuracy; interobserver agreement; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; proton density fat fraction; quantitative imaging biomarkers; quantitative ultrasound.

Fig. 1. Box-and-whisker plots of pairwise comparisons of all imaging measures

A–D, Graphs show comparisons between histology-determined steatosis grades and conventional ultrasound (CUS) consensus scores (A), two-analyst mean attenuation coefficient (B) and backscatter coefficient (C), and mean right liver lobe MRI-estimated proton density fat fraction (PDFF) (D). All imaging-determined values were plotted as median (dashed lines), 25th to 75th percentile (box), and maximum and minimum values (whiskers) for each histology-determined steatosis grade. Horizontal brackets over plots indicate statistical significance as determined by Mann-Whitney test; *p < 0.05, **p < 0.01, and ***p < 0.001. NS = not significant.

Fig. 2

Three patients with grade 1 (36-year-old woman), grade 2 (27-year-old man), and grade 3 (22-year-old man) steatosis as determined by histologic examination. Top row shows conventional ultrasound (CUS) B-mode images for each patient, which were used by radiologists for conventional scoring. Second row shows quantitative ultrasound images for same three patients with blue line outlining fields of interest as determined by one study image analyst. Third and fourth rows show parametric color-coded maps for attenuation coefficient (0–2 dB/cm-MHz) and backscatter coefficient (0–0.25 1/sr-cm), respectively. Red indicates higher values and blue indicates lower values.

Fig. 3

Classification tables showing number of correctly classified (shaded boxes) and incorrectly classified (unshaded boxes) patients for each histologic steatosis grade for each imaging measure. Tables represent Classification data based on two-radiologist consensus conventional ultrasound (CUS) scores, two-analyst mean quantitative ultrasound scores (attenuation and backscatter coefficients), or MRI-estimated proton density fat fraction (PDFF) scores.

Fig. 4. Bland-Altman limits of agreement

A and B, Graphs show mean interobserver agreement and differences for attenuation coefficients (A) and backscatter coefficients (B) calculated by each research analyst. One substantial outlier is not shown (interobserver mean = 0.40 1/sr-cm; interobserver difference = 0.76 1/sr-cm) for backscatter coefficient plot (B) for clarity. Black dotted lines represent mean difference, and black solid lines represent 95% Bland-Altman limits of agreement.