Diagnostic criteria of perfluorobutane-enhanced ultrasonography for diagnosing hepatocellular carcinoma in high-risk individuals: how is late washout determined?

Abstract

Purpose: The aim of this study was to investigate the optimal washout criteria of perfluorobutane-enhanced ultrasonography (PFB-US) for the diagnosis of hepatocellular carcinoma (HCC) in high-risk individuals.

Methods: Participants at risk of HCC with treatment-naïve solid hepatic observations (≥1 cm) who underwent PFB-US from March 2019 to September 2020 were prospectively recruited. Arterial phase hyperenhancement (APHE), washout time, and washout degree were evaluated. The diagnosis of HCC was made by non-rim APHE with late and mild washout. The per-lesion diagnostic performance for diagnosing HCC using different cutoffs for late washout (50, 55, 60, 65, and 70 seconds postcontrast) and the different time windows for determining washout (until 2, 3, 4, 5, 6, 7, 8, 9, and 10 minutes postcontrast) were compared using the McNemar test.

Results: In total, 101 participants with 113 observations (mean size, 33.5±2.8 mm; HCCs [n=82], non-HCC malignancies [n=16], benign [n=15]) were evaluated. Non-rim APHE was observed in 86.6% (71/82) of HCCs. As the cutoff time for late washout increased, the specificity increased to 100% (95% confidence interval [CI], 88.8% to 100%) at the 60-second cutoff with 62.2% sensitivity (95% CI, 50.8% to 72.7%). When the time window for determining washout became wider, the sensitivity and accuracy increased until 6 minutes, with 100% specificity at all times.

Conclusion: Determining washout within 6 minutes after contrast injection with a 60-second cutoff for late washout showed the highest sensitivity without losing specificity for diagnosing HCC using PFB-US in individuals at high risk.

Keywords: Contrast-enhanced ultrasonography; Hepatocellular carcinoma; Perfluorobutane.

Fig. 1.. Flow diagram of the study sample.

CEUS, contrast-enhanced ultrasonography; HCC, hepatocellular carcinoma.

Fig. 2.. A 54-year-old man with pathologically confirmed hepatocellular carcinoma in segment 6 of the liver.

A. On dynamic computed tomography, only a 1.8-cm tubular hypoattenuating observation without arterial phase hyperenhancement (APHE) is noted in the arterial phase (arrows). B. This observation shows a wider extent of washout in the delayed phase (arrows). C. On perfluorobutane-enhanced ultrasonography, a 3.1-cm APHE observation in segment 6 presented mild washout 62 seconds after contrast agent injection (D, arrows). E. These observations presented mild defects in the Kupffer phase, which was defined as starting 10 minutes after contrast injection (arrows).

Fig. 3.. A 2.4-cm hypoechoic observation of liver segment 2 during ultrasound surveillance in a 72-year-old woman with chronic hepatitis B and nonalcoholic fatty liver disease.

A, B. On perfluorobutane-enhanced ultrasonography, this observation did not present hyperenhancement in the arterial phase. (arrow) (A), but mild washout 90 seconds after contrast injection was noted (arrows) (B). C. This observation presented isoechogenicity in the Kupffer phase, which was defined as starting 10 minutes after contrast injection (arrow). D. This observation was not delineated on a 1-year follow-up dynamic abdominal computed tomography examination and was presumed to be a benign lesion.

Fig. 4.. A 3-cm noninvasively diagnosed hepatocellular carcinoma in segment 3 of the liver during ultrasound surveillance in a 50-year-old man with chronic hepatitis B.

A, B. On perfluorobutane-enhanced ultrasonography, this observation presents hyperenhancement in the arterial phase (arrows) (A) and mild washout 65 seconds after contrast injection (arrows) (B). C. This observation presented isoechogenicity in the Kupffer phase, which was defined as starting 10 minutes after contrast injection (arrows).

Fig. 5.. Comparison of the echogenicity of hepatic observations between the vascular phase and the Kupffer phase.

Hepatic observations were performed without rim arterial phase hyperenhancement or peripheral globular enhancement. The vascular phase was defined as the period until 6 minutes after contrast injection. The grayscale represents the echogenicity in the Kupffer phase. No hepatocellular carcinoma (HCC) without washout in the vascular phase presented hypoechogenicity in the Kupffer phase. There were no benign observations showing marked washout or marked hypoechogenicity in the Kupffer phase. WO, washout.

Fig. 6.. Time distribution of mild hypoechogenicity in perfluorobutane-enhanced ultrasonography.

The analysis was performed for hepatic observations without rim arterial phase hyperenhancement, peripheral globular enhancement, or marked washout. Ninety-two percent (73 of 79) of hepatocellular carcinomas (HCCs), 66.7% (6 of 9) non-HCC malignancy, and 36.4% (4/11) of benign lesions presented mild hypoechogenicity. Mild washout of HCC was most frequent 70-120 seconds after contrast injection (26 of 73, 35.6%). Sixteen percent (12 of 73) of HCCs showed mild washout before 50 seconds, and 4.1% (3 of 73) of HCCs did between 50-60 seconds. Every non-HCC malignancy (n=6) presented mild washout before 60 seconds. One benign lesion (1 of 4, 25%) presented mild washout before 50 seconds, and the other three lesions (3 of 4, 75%) presented mild washout after 70 seconds.