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

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 (RDCDDDO) pooled across systems for SWE and individually for VCTE. Secondary end points included system-specific RDCDDDO, same-day, same-operator repeatability coefficient (RCSDSO), and between-system same-day, same-operator reproducibility coefficient. The planned sample provided 80% power to detect a pooled RDCDDDO 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. RDCDDDO was 30.7% (95% upper bound, 34.4%) for SWE and 35.6% (95% upper bound, 43.9%) for VCTE. SWE system-specific RDCDDDO varied from 24.2% to 34.3%. The RCSDSO 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, RDCDDDO less than 35%, with VCTE having a higher RDCDDDO. 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.

Assessment of S-Glutathionylated Rac1 in Cells Using Biotin-Labeled Glutathione.

Rac1 is a member of the family of small Rho GTPases that are molecular switches governing a variety of fundamental cellular processes, such as cell growth and motility. Its subcellular location and activity are regulated by several posttranslational modifications. S-glutathionylation, the adduction of glutathione to cysteine residues in Rac1, is a redox-dependent thiol modification and is generally associated with oxidative/nitrosative stress, representing a novel mechanism of GTPase regulation. Here, we describe the use of biotin-labeled glutathione to monitor intracellular glutathionylated Rac1 in response to exogenous stimuli.