Proof of Concept: Super-Resolution Ultrasound and Viscoelastic Imaging of Hepatic Microcirculation for Early Detection and Staging of Liver Fibrosis in a Murine Model.

Abstract

Objectives: Super-resolution ultrasound microvascular imaging (SRUS) has emerged as a noninvasive technology capable of visualizing the microvasculature with exceptional spatial resolution, surpassing the acoustic diffraction limit. This study aims to assess the potential of SRUS in staging liver fibrosis by evaluating its diagnostic performance against ultrasound viscosity imaging.

Methods: Liver fibrosis was induced by carbon tetrachloride (CCl₄) in 30 mice. The mice were evenly distributed across five stages (6 mice per stage), categorized from F0 (no fibrosis) to F4 (cirrhosis) based on the extent of collagen deposition. SRUS microvascular imaging and ultrasound viscosity imaging were compared for their efficacy in detecting liver fibrosis stages. Immunohistochemistry and histopathological analyses were conducted to correlate vessel density and collagen deposition.

Results: SRUS effectively detected microvascular changes across all fibrosis stages. Significant vessel diameter enlargement was observed at early stages (F1), with further increases in advanced stages (F3-F4). Vessel density significantly decreased in later stages, indicating compromised angiogenesis. Ultrasound viscosity imaging showed marked viscoelastic reductions in fibrosis but lacked sensitivity in early-stage detection. SRUS parameters exhibited strong correlations with histological findings, underscoring their potential diagnostic value. Receiver operating characteristic (ROC) curve analysis further demonstrated the superior sensitivity of SRUS (89.59% [95% confidence interval (CI): 84.87-92.96%]), particularly in distinguishing early-stage fibrosis (F0-F1) from advanced stages (F2-F4) (area under the curve [AUC] = 0.9610, 95% CI: 0.9449-0.9771; P < .001).

Conclusions: SRUS microvascular imaging is a promising adjunct to traditional elastography, offering enhanced sensitivity for early-stage liver fibrosis detection. It provides critical insights into microcirculatory dysfunction, complementing stiffness measurements and aiding in accurate diagnosis.