Super-Resolution Contrast-Enhanced Ultrasound Examination Down to the Microvasculature Enables Quantitative Analysis of Liver Lesions: First Results

Abstract

This article investigates the first use of dynamic microvascularization of liver lesions in clinical evaluation using real-time super-resolution contrast-enhanced ultrasound (SR CEUS). A retrospective analysis of SR CEUS examinations of liver lesions was performed. All examinations were conducted using an SC7-1U convex probe after the bolus injection of the ultrasound contrast agent. Digital cine loops were stored for independent evaluation. The evaluation was performed with respect to parallel measuring lines (the diameter corresponded to the capillary density) in the area of the reference lesion, liver tissue, and liver capsule using statistical analysis. In total, 65 patients (female n = 28; male n = 37; average age 57.8 ± 17.2 years) were evaluated. The examined liver lesions were mostly benign masses (n = 46). Mild liver fibrosis (stage F1) was present in most cases (n = 35). The lesions examined were located at an average tissue depth of 6.07 ± 2.47 cm. The highest number of lesion measurements was observed in the malignant lesion group. Significant differences in the measurements were found when comparing benign lesions with the capillary region (p < 0.001) and normal liver tissue (p < 0.01). The use of SR CEUS opens up new possibilities for the quantification of neovascularization, assessment of microvascular changes, and evaluation of the follow-up of intrahepatic interventions.

Keywords: contrast agent; intervention; liver; microvascularization; ultrasonography.

Figure 1

Examination of the liver using SR CEUS: 1. Imaging of liver vessels in the intercostal section using SR CEUS technology. 2. Determination of ROIs. 3. ROIs are surveyed using structure-based lines.

Figure 2

Predicted probabilities of SR CEUS ratings 3 to 5 (adequate, good and excellent, respectively) depending on the lesion depth (cm), defined as the distance from the skin to the center of the lesion, as estimated from an ordinal regression model (see Table A1 in the Appendix A). The model’s predictions are accompanied by 95% confidence bands (shaded area).

Figure 3

Box–violin plots comparing the different liver regions for malignant (a) and benign (b) cases, the intervention group (c), and patients with Morbus Osler (d). For a complete list of p-values, see Table A2 in the Appendix A. * p < 0.05, *** p < 0.001.

Figure 4

Box–violin plots comparing the measurements in the capillary bed (a), ordinary liver (b), and lesion (c) between the four groups. No significant differences were detected between the groups (see Table A3, Table A4 and Table A5 in the Appendix A).

Figure 5

The predicted probability of zero measurement for the lesion in the four groups with 95% confidence intervals. The probabilities were estimated using a logistic regression model and are adjusted for age (see Table A4 in the Appendix A).