Fluctuational Imaging for the Diagnosis of Hepatic Hemangioma: A Multicenter, Prospective Study

[Study Population and Sample Size] This is an exploratory, prospective, multicenter study. A predefined sample size is not required. With an estimated enrollment of approximately 100 cases per institution over one year and participation of four institutions, approximately 400 cases are expected.

[Eligibility Criteria] Eligible participants are adults aged 19 years or older with a focal hepatic lesion ≥1 cm that has been definitively diagnosed or is expected to be diagnosed within one month after FLI examination, and who provide informed consent. Patients unable to hold their breath for at least 5 seconds, those with inadequate B-mode image quality, lesions <1 cm on ultrasound, or without definitive diagnosis within one month are excluded.

[Reference Standard] The reference standard for lesion diagnosis was defined as follows: hepatic hemangiomas were confirmed by histopathology or by typical imaging features with size stability for at least two years; hepatocellular carcinoma was confirmed by histopathology or by the presence of an LR-5 lesion in patients with liver cirrhosis; all other hepatic lesions (including metastasis, cholangiocarcinoma, adenoma, focal nodular hyperplasia, and angiomyolipoma) required histopathological confirmation.

[Study Design and Statistical Analysis] After informed consent, FLI is performed on the target lesion. FLI maps are anonymized and independently reviewed by four readers, each classifying findings as positive or negative. The primary endpoint is comparison of FLI-positive proportions between hemangioma and non-hemangioma groups using chi-square or Fisher's exact tests. Interreader agreement will be evaluated using Fleiss' kappa. The secondary endpoint of this study is to explore how the diagnostic performance of FLI for hepatic hemangioma varies according to lesion echogenicity and lesion depth. Continuous variables will be analyzed using Student's t-test or Mann-Whitney U test, as appropriate. A p-value < 0.05 will be considered statistically significant.

Inclusion criteria

• Adults aged 19 years or older.
• Presence of a focal hepatic lesion measuring 1 cm or larger on ultrasonography.
• Lesion diagnosis established by pathology or lesion-specific imaging reference standards, or expected to be definitively established within 1 month after the FLI examination.
• Ability and willingness to provide written informed consent.

Exclusion criteria

• Inability to maintain stable breath-holding for at least 5 seconds during ultrasonography.
• Inadequate B-mode ultrasound image quality of the target lesion due to factors such as acoustic shadowing or severe beam attenuation.
• Target lesion measuring less than 1 cm on ultrasonography.
• Failure to establish a definitive diagnosis within 1 month after the FLI examination.