HemangiomaNCT07418294
Fluctuational Imaging for the Diagnosis of Hepatic Hemangioma: A Multicenter, Prospective Study
An observational study of Hemangioma, run by Yonsei University at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hemangioma
- How many people
- 400 participants
- Where
- 1 siteSouth Korea
- Study dates
- 2 Jan 2026to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Severance hospital, Yonsei university college of medicine
Seoul, Seodaemun-gu, 03722
Seung-seob Kim, Professor, 82) 10-2600-0127, k2s0127@yuhs.ac
About this study
[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.
Read more
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.
Read the detailed description
[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.
- Conditions
- Hemangioma
- Medical subject headings
- Hemangioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Periprocedural
Secondary outcomes (2)
Echogenicity of liver lesion
The echogenicity of the target liver lesion is assessed on ultrasonography and recorded as one of the following categories: hyperechoic, hypoechoic, or mixed.
Measured: Periprocedural
Depth of liver lesion
The depth of the target liver lesion is assessed on ultrasonography by measuring the distance from the ultrasound probe to the lesion and is recorded in centimeters.
Measured: Periprocedural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2026
- Study start2 Jan 2026
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HemangiomaStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Seung-seob Kim, Professor, Principal investigator, Severance Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07418294
- Sponsor's protocol ID
- 1-2024-0043
- Status last verified
- Feb 2026
- First submitted
- 2 Feb 2026
- Last updated
- 18 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluctuational Imaging for the Diagnosis of Hepatic Hemangioma: A Multicenter, Prospective Study
- ClinicalTrials.gov ID
- NCT07418294
- Acronym / sponsor ID
- 1-2024-0043
- Conditions
- Hemangioma
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 2 Jan 2026 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 18 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
[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.
Detailed description
[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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
FLI-positivity
Time frame: Periprocedural
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.
2 secondary outcomes
Echogenicity of liver lesion
Time frame: Periprocedural
Depth of liver lesion
Time frame: Periprocedural
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Seung-seob Kim, Professor principal investigator
Severance Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemangioma, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Seung-seob Kim, Professor (82) 10-2600-0127, k2s0127@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FLI-positivity (time frame: Periprocedural). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.