CEUS-based quantitative analysis of washout time in focal liver lesions affects hepatocellular carcinoma diagnosis

According to the American Association for the Study of Liver Diseases (AASLD) 2023 guidelines, contrast-enhanced ultrasound (CEUS) is a valuable complementary imaging modality for characterizing focal liver lesions (FLLs) that are not definitively diagnosed by contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (CEMRI). This study compared the washout time of FLLs assessed by quantitative analysis (QA) and visual analysis (VA) on CEUS, evaluated their effects on CEUS Liver Imaging Reporting and Data System (LI-RADS) classification, and assessed their diagnostic performance in hepatocellular carcinoma (HCC). Furthermore, we sought to identify the QA-derived optimal washout time threshold for HCC diagnosis.

Patients at high risk for HCC who underwent CEUS examinations at our hospital between April 2020 and October 2021 were retrospectively enrolled. All FLLs were pathologically confirmed. Washout time was assessed quantitatively using VueBox® software (QA) and visually by radiologists (VA). LR-5 was defined by CEUS LI-RADS (2017) as the category indicating liver lesions that are definitely HCC. QA LR-5 and VA LR-5 were defined as LR-5 categories assigned according to CEUS LI-RADS (version 2017) based on QA and VA, respectively. Furthermore, a modified washout time threshold was applied in the QA group to determine the optimal cutoff for HCC diagnosis, resulting in a new category termed "modified QA LR-5". The Wilcoxon signed-rank test was used to compare the washout time between QA and VA, and the diagnostic performance of VA LR-5, QA LR-5, and modified QA LR-5 for HCC was compared using the McNemar test.

A total of 233 FLLs from 225 patients were included, comprising 220 malignant lesions (184 HCCs) and 13 benign lesions. Median washout time of all FLLs was 55-59 seconds by QA and ≥60 seconds by VA (Z=-6.185, P<0.001). For HCCs, the median washout time was ≥60 seconds with both QA and VA, although QA detected earlier onset (Z=-6.022, P<0.001). For HCC diagnosis, QA LR-5 showed lower sensitivity (51.6% vs. 66.3%, P<0.001), accuracy (60.5% vs. 72.1%, P<0.001) and area under the receiver operating characteristic curve (AUC) (0.728 vs. 0.801, P<0.001) than VA LR-5, while maintaining comparable specificity (93.9% vs. 93.9%, P>0.05). With a 40-second threshold, modified QA LR-5 significantly improved in sensitivity (79.9% vs. 66.3%, P<0.001) and accuracy (80.7% vs. 72.1%, P<0.001), without significant loss of specificity (83.7% vs. 93.9%, P>0.05) or AUC (0.818 vs. 0.801, P>0.05) compared with VA LR-5.

QA reveals earlier washout than VA, while both methods show good agreement with CEUS LI-RADS classification. Modifying the washout threshold from 60 to 40 seconds significantly improves the diagnostic performance of QA LR-5, supporting recalibration of CEUS LI-RADS for quantitative assessment, likely because QA is more sensitive in detecting early contrast clearance.