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

NCT07418294 | Recruiting

• 1 other identifier: 1-2024-0043
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

\[Background and Rationale\] Hepatic hemangioma is the most common benign tumor of the liver, with a reported prevalence of up to 20% in the general population. On B-mode ultrasonography, a typical hemangioma appears as a well-defined hyperechoic lesion compared with the surrounding liver parenchyma. However, hyperechogenicity is observed in only approximately 70% of cases, while the remaining lesions may appear hypoechoic or mixed echogenic. Additional sonographic features such as posterior acoustic enhancement or an echogenic rim may aid diagnosis, but none are specific to hemangioma. Consequently, contrast-enhanced CT or MRI is commonly required for definitive diagnosis, even when a hemangioma is strongly suspected on conventional ultrasound. In 2020, Kobayashi et al. (Ultrasound Med Biol 2021;47:941-946)reported a novel ultrasound finding termed the "fluttering sign," defined as continuous motion of tiny hyperechoic dots within a hemangioma during real-time scanning. Although the precise mechanism has not been experimentally validated, this phenomenon is presumed to reflect motion of acoustic scatterers, mainly red blood cells, induced by the ultrasound beam. The fluttering sign was observed in approximately 39% of hyperechoic hemangiomas and in up to 85% of hypoechoic or mixed-echoic hemangiomas, suggesting potential lesion specificity. A major limitation of the fluttering sign is its subjectivity, as visual assessment during real-time ultrasound is highly operator-dependent. To address this limitation, Imamura et al. (Sci Rep 2022;12:4701) developed a computer-based algorithm named Fluctuational Imaging (FLI), which objectively quantifies fluttering motion. FLI demonstrated almost perfect agreement with visual assessment of the fluttering sign (Cohen's kappa = 0.95). \[Study Objectives\] Although FLI is theoretically expected to be specific to hemangiomas, no study has systematically evaluated its behavior across a broad spectrum of non-hemangioma hepatic lesions. The primary objective of this study is to investigate whether the proportion of FLI-positive findings is significantly higher in hepatic hemangiomas than in non-hemangioma liver lesions. \[Risk-Benefit Assessment\] FLI is based on conventional diagnostic ultrasound physics and does not impose additional risk to patients. If FLI enables confident diagnosis of hepatic hemangioma using ultrasound alone, it may reduce unnecessary contrast-enhanced CT or MRI examinations, thereby decreasing healthcare costs, radiation exposure, and contrast-related risks. Overall, the anticipated benefits outweigh potential risks.

Conditions

Hemangioma

Outcome Measures

Primary Outcomes (1)

• FLI-positivity

  FLI is performed on the target liver lesion. The resulting FLI maps are anonymized and independently reviewed by four readers, each classifying the findings as positive or negative according to predefined criteria. An FLI finding is considered positive when a high-signal-intensity area is present within the target lesion relative to the surrounding liver parenchyma; otherwise, it is considered negative. For the final determination, a lesion is classified as FLI-positive when at least three of the four readers rate it as positive.

  Periprocedural

Secondary Outcomes (2)

• Echogenicity of liver lesion

  Periprocedural

• Depth of liver lesion

  Periprocedural

Study Arms (2)

Hepatic hemangioma

Patients with focal hepatic lesions diagnosed as hepatic hemangioma based on predefined reference standards.

Non-hemangioma hepatic lesions

Patients with focal hepatic lesions diagnosed as non-hemangioma hepatic tumors, including benign and malignant lesions, based on predefined reference standards.

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This prospective, multicenter study will enroll adult patients (≥19 years) from four university-affiliated tertiary hospitals in South Korea who have focal hepatic lesions measuring 1 cm or larger on ultrasonography. Eligible participants must have a definitive diagnosis established by pathology or lesion-specific imaging reference standards, or be expected to receive a definitive diagnosis within one month after the FLI examination. The study population will include patients with hepatic hemangiomas as well as a broad spectrum of non-hemangioma hepatic lesions, including both benign and malignant tumors.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance hospital, Yonsei university college of medicine

Seoul, Seodaemun-gu, 03722, South Korea

RECRUITING

MeSH Terms

Conditions

Hemangioma

Condition Hierarchy (Ancestors)

Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Seung-seob Kim, Professor

  Severance Hospital, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seung-seob Kim, Professor

CONTACT

82) 10-2600-0127; k2s0127@yuhs.ac

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 18, 2026
• Study Start: January 2, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

KR (1)