Multimodal Ultrasound for Differentiating Lymphedema and Lipedema

ULTRASONOGRAPHIC EVALUATION OF LOWER EXTREMITY SKIN AND SUBCUTANEOUS TISSUE WITH QUANTITATIVE ECHOGENICITY AND ELASTOGRAPHY IN LYMPHEDEMA, LIPEDEMA, AND HEALTHY CONTROL GROUPS: A CONTROLLED CLINICAL STUDY

The aim of this observational study is to evaluate the diagnostic value of multimodal ultrasonography in differentiating between lymphedema and lipedema. Differentiating these two chronic conditions based solely on clinical examination can be challenging due to overlapping symptoms. This study will utilize various non-invasive ultrasound techniques-including B-mode ultrasound, strain elastography, power Doppler, and quantitative ImageJ analysis-to compare tissue characteristics among patients with lymphedema, patients with lipedema, and healthy controls. The goal is to identify reliable, non-invasive imaging biomarkers that can facilitate early and accurate diagnosis, thereby optimizing patient management.

Study Overview

• Status: Recruiting
• Conditions: Lymphedema; Lipedema
• Intervention / Treatment: Diagnostic test: Multimodal Ultrasound Assessment

Detailed Description

Lymphedema and lipedema are distinct pathological entities that often present with similar clinical features, particularly in the lower extremities. Accurate differential diagnosis is crucial for appropriate therapeutic intervention. While modalities like lymphoscintigraphy serve as standard diagnostic tools for lymphedema, they are invasive and not universally accessible. High-resolution ultrasonography provides a practical, non-invasive alternative for tissue assessment.

This cross-sectional, observational study will recruit participants and categorize them into three groups: a lymphedema group, a lipedema group, and a healthy control group. Comprehensive multimodal ultrasound evaluations will be performed on all participants. The assessment protocol includes:

B-mode Ultrasonography: To measure the thickness of the dermis and subcutaneous tissue layers.

Strain Elastography: To evaluate the biomechanical properties and relative stiffness of the affected tissues.

Power Doppler: To assess the local microvascularity and blood flow patterns.

ImageJ Software Analysis: To perform quantitative pixel-based echogenicity evaluation of the ultrasound images.

By systematically comparing these ultrasonographic parameters across the three groups, this study aims to establish standard, reproducible imaging criteria. The primary objective is to determine which specific ultrasound modalities, or combinations thereof, offer the highest diagnostic accuracy in differentiating lymphedema from lipedema in clinical practice.

• Study Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

• Study Contact: Name: Abdullah Goktug Yazar; Phone Number: +905309731140; Email: abdullahgoktug.yazar@sbu.edu.tr

Study Locations

• Turkey (Türkiye)
  • Kocasinan
    • Kayseri, Kocasinan, Turkey (Türkiye), 38080
      • Recruiting
      • Kayseri City Hospital
      • Contact: Abdullah Goktug Yazar, MD; Phone Number: +905309731140; Email: abdullahgoktug.yazar@sbu.edu.tr
      • Sub-Investigator: Ayse Guc, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients presenting to the Physical Medicine and Rehabilitation outpatient clinic with complaints of lower extremity swelling, diagnosed clinically with either lymphedema or lipedema. A healthy control group, matched for general demographic characteristics, will be recruited from volunteers without any lower extremity pathologies.

Description

Inclusion Criteria:

Individuals aged 18 to 75 years.

Clinical diagnosis of lower extremity lymphedema (for the lymphedema group).

Clinical diagnosis of lower extremity lipedema (for the lipedema group).

Healthy individuals with no history or clinical signs of chronic lower extremity edema (for the control group).

Exclusion Criteria:

Presence of active local infections, such as cellulitis or erysipelas, in the lower extremities.

History of deep vein thrombosis (DVT) or severe chronic venous insufficiency.

Systemic conditions that can cause secondary edema, including congestive heart failure, chronic kidney disease, or severe hepatic impairment.

Previous surgical interventions on the affected lower extremities, including liposuction, lymphatic reconstructive surgery, or major orthopedic surgeries.

Active malignancy or currently undergoing radiotherapy/chemotherapy.

Pregnancy or lactation.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lymphedema Group; Patients clinically diagnosed with lower extremity lymphedema. Participants in this group will undergo a non-invasive multimodal ultrasound assessment (including B-mode, strain elastography, power Doppler, and ImageJ analysis) to evaluate tissue characteristics.	Diagnostic test: Multimodal Ultrasound Assessment; A comprehensive, non-invasive ultrasonographic evaluation of the lower extremities. The protocol includes B-mode ultrasound for measuring dermis and subcutaneous tissue thickness, strain elastography for assessing tissue biomechanical stiffness, and Power Doppler for evaluating local microvascularity. Additionally, quantitative echogenicity of the tissues will be analyzed using ImageJ software.; Other Names: B-mode Ultrasonography; Strain Elastography; Power Doppler; ImageJ Analysis
Lipedema Group; Patients clinically diagnosed with lipedema of the lower extremities. Participants in this group will undergo the identical non-invasive multimodal ultrasound assessment protocol to evaluate tissue echogenicity, thickness, and stiffness.	Diagnostic test: Multimodal Ultrasound Assessment; A comprehensive, non-invasive ultrasonographic evaluation of the lower extremities. The protocol includes B-mode ultrasound for measuring dermis and subcutaneous tissue thickness, strain elastography for assessing tissue biomechanical stiffness, and Power Doppler for evaluating local microvascularity. Additionally, quantitative echogenicity of the tissues will be analyzed using ImageJ software.; Other Names: B-mode Ultrasonography; Strain Elastography; Power Doppler; ImageJ Analysis
Healthy Control Group; Healthy volunteers with no history or clinical signs of chronic lower extremity edema, lymphedema, or lipedema. This group will undergo the same multimodal ultrasound assessment to establish baseline normative values for comparison.	Diagnostic test: Multimodal Ultrasound Assessment; A comprehensive, non-invasive ultrasonographic evaluation of the lower extremities. The protocol includes B-mode ultrasound for measuring dermis and subcutaneous tissue thickness, strain elastography for assessing tissue biomechanical stiffness, and Power Doppler for evaluating local microvascularity. Additionally, quantitative echogenicity of the tissues will be analyzed using ImageJ software.; Other Names: B-mode Ultrasonography; Strain Elastography; Power Doppler; ImageJ Analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dermal and Subcutaneous Tissue Thickness	Measurement of the dermal and subcutaneous tissue layers in millimeters (mm) using high-resolution B-mode ultrasonography to identify anatomical differences between the groups.	Day 1 (At the time of ultrasound assessment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue Stiffness Assessment via Strain Elastography	Evaluation of the biomechanical properties and relative stiffness of the subcutaneous tissue, assessed through color-coded elastogram scoring maps.	Day 1 (At the time of ultrasound assessment)
Quantitative Echogenicity Analysis	Pixel-based quantitative evaluation of tissue echogenicity from ultrasound images, analyzed using ImageJ software to establish objective imaging biomarkers.	Day 1 (At the time of ultrasound assessment)
Visual Analogue Scale (VAS) for Pain	Assessment of the intensity of lower extremity pain reported by the participants on a scale from 0 (no pain) to 10 (worst imaginable pain).	Day 1 (Baseline clinical evaluation)

Collaborators and Investigators

• Sponsor: Kayseri City Hospital

Publications and helpful links

General Publications

• Mortimer PS, Rockson SG. New developments in clinical aspects of lymphatic disease. J Clin Invest. 2014 Mar;124(3):915-21. doi: 10.1172/JCI71608. Epub 2014 Mar 3.
• Gerard N, Farmakis IT, Valerio L, Hobohm L, Keller K, Kucher N, Barco S, Grigorean A. Epidemiological Study of Lymphedema Prevalence and Comorbidities in Hospitalized Patients in the United States. J Clin Med. 2025 Nov 17;14(22):8156. doi: 10.3390/jcm14228156.
• Rockson SG. Lymphedema. Am J Med. 2001 Mar;110(4):288-95. doi: 10.1016/s0002-9343(00)00727-0.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 15, 2026

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Differential Diagnosis; Multimodal Ultrasonography; Strain Elastography; Power Doppler; ImageJ Analysis; Subcutaneous Tissue
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Lymphatic Diseases; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Lymphedema; Lipedema
• Other Study ID Numbers: 2025-564

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared publicly to maintain participant confidentiality and in accordance with the policies of the institutional ethics committee. However, the study protocol and statistical analysis plan may be available upon reasonable request to the principal investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No