Reproducibility and Repeatability of US Shear-Wave and Transient Elastography in Nonalcoholic Fatty Liver Disease

Abstract

Background US shear-wave elastography (SWE) and vibration-controlled transient elastography (VCTE) enable assessment of liver stiffness, an indicator of fibrosis severity. However, limited reproducibility data restrict their use in clinical trials. Purpose To estimate SWE and VCTE measurement variability in nonalcoholic fatty liver disease (NAFLD) within and across systems to support clinical trial diagnostic enrichment and clinical interpretation of longitudinal liver stiffness. Materials and Methods This prospective, observational, cross-sectional study (March 2021 to November 2021) enrolled adults with NAFLD, stratified according to the Fibrosis-4 (FIB-4) index (≤1.3, >1.3 and <2.67, ≥2.67), at two sites to assess SWE with five US systems and VCTE with one system. Each participant underwent 12 elastography examinations over two separate days within 1 week, with each day's examinations conducted by a different operator. VCTE and SWE measurements were reported in units of meters per second. The primary end point was the different-day, different-operator reproducibility coefficient (RDC_DDDO) pooled across systems for SWE and individually for VCTE. Secondary end points included system-specific RDC_DDDO, same-day, same-operator repeatability coefficient (RC_SDSO), and between-system same-day, same-operator reproducibility coefficient. The planned sample provided 80% power to detect a pooled RDC_DDDO of less than 35%, the prespecified performance threshold. Results A total of 40 participants (mean age, 60 years ± 10 [SD]; 24 women) with low (n = 17), intermediate (n = 15), and high (n = 8) FIB-4 scores were enrolled. RDC_DDDO was 30.7% (95% upper bound, 34.4%) for SWE and 35.6% (95% upper bound, 43.9%) for VCTE. SWE system-specific RDC_DDDO varied from 24.2% to 34.3%. The RC_SDSO was 21.0% for SWE (range, 13.9%-35.0%) and 19.6% for VCTE. The SWE between-system same-day, same-operator reproducibility coefficient was 52.7%. Conclusion SWE met the prespecified threshold, RDC_DDDO less than 35%, with VCTE having a higher RDC_DDDO. SWE variability was higher between different systems. These estimates advance liver US-based noninvasive test qualification by (a) defining expected variability, (b) establishing that serial examination variability is lower when performed with the same system, and (c) informing clinical trial design. ClinicalTrials.gov Identifier NCT04828551 © RSNA, 2024 Supplemental material is available for this article.

Graphical abstract

Figure 1:

Study inclusion and exclusion flowchart. FIB-4 = Fibrosis-4 index, NAFLD = nonalcoholic fatty liver disease, SWE = shear-wave elastography, VCTE = vibration-controlled transient elastography.

Figure 2:

Diagram shows Non-Invasive Biomarkers of Metabolic Liver Disease 1.1 imaging visit design. All study participants underwent two imaging visits, although each visit used different combinations of US and vibration-controlled transient elastography (VCTE) systems. One VCTE examination was performed at visit 1 and two VCTE examinations were performed at visit 2 for each participant. Three of the five US systems were used at visit 1. Two US systems were repeated at visit 1. The same three systems were used in visit 2, with the third system being repeated. All US systems were used on an equal number of participants. The sample of US systems allocated to each participant was randomly selected before study initiation.

Figure 3:

Representative multisystem shear-wave elastography (SWE) images. (A) Images obtained with a Philips machine in a 61-year-old female. Color map shows shear-wave speed (SWS), which is quantified by the inset region of interest, also used in B, D, and E. (B) Images obtained with a Canon machine in a 61-year-old male. Smooth, parallel lines in the propagation map indicate areas of high SWE measurement quality. Attenuation, shear-wave propagation, and shear-wave dispersion maps were acquired simultaneously. (C) Image obtained with a Siemens machine in a 70-year-old female. SWS is estimated with use of 15 sectors. More dots indicate higher stiffness per sector. Ultrasound-derived fat fraction (UDFF) is estimated simultaneously. (D) Image obtained with a GE machine in a 59-year-old female. A yellow region of interest indicates a technically adequate measurement. (E) Images obtained with a Supersonic machine in a 61-year-old male. Viscosity was estimated simultaneously.

Figure 4:

Representative image from vibration-controlled transient elastography examination in a 70-year-old female participant. The median liver stiffness, 4.5 kPa, corresponds to a median shear-wave speed of 1.23 m/sec as calculated from the 10 individual measurements shown. For each measurement, time motion (TM) mode, A mode, and the automated liver targeting tool were used to ensure correct device placement. The resulting elastogram enables estimation of liver stiffness. The controlled attenuation parameter (CAP) is acquired and reported simultaneously but was not analyzed in this study.

Figure 5:

Optimal shear-wave speed (SWS) measurement technique. A representative B-mode liver US is shown with superimposed SWS color sector map and inset region of interest to quantify SWS. The region of interest center should be placed less than 6.5 cm of the skin surface (red line) and more than 2.0 cm from the liver capsule (yellow line). When the skin-to-capsule distance (blue line) is greater than 4.5 cm, as can occur with obesity, both constraints cannot be met and distance from the liver capsule should be prioritized. The region of interest should be preferentially placed in the image midline without overlapping vessels, large bile ducts, or imaging artifacts.