Contrast Enhanced Ultrasound Medical Imaging for Identifying Breast Masses

Characterizing Breast Masses Using an Integrative Framework of Machine Learning and Radiomics

This clinical trial investigates the role of contrast enhanced ultrasound (CEUS) in identifying cystic breast masses as benign or malignant. Ultrasound is a diagnostic imaging test that uses sound waves to make pictures of the body without using radiation (x-rays). Ultrasounds are widely used to diagnose many diseases in the body. This trial may help researchers learn if using CEUS will help in determining whether or not an ultrasound guided biopsy is necessary.

Study Overview

• Status: Recruiting
• Conditions: Breast Carcinoma
• Intervention / Treatment: Procedure: Contrast-Enhanced Ultrasound; Drug: Sulfur Hexafluoride Lipid Microspheres; Drug: Perflutren Lipid Microspheres

Detailed Description

PRIMARY OBJECTIVES:

I. To examine and compare the distribution of CEUS parameters in breast masses that were evaluated as Breast Imaging Reporting and Data System (BI-RADS) 4a, 4b, 4c or 5 by conventional ultrasound (US) and were recommended for ultrasound guided biopsy, and to evaluate whether these parameters can be used to classify suspicious cystic-appearing breast masses as benign or malignant.

Ia. To develop a CEUS-based radiomics workflow to extract radiomic metrics (> 1600 features) in classifying breast mass malignancy (Radiomics).

Ib. To develop a systematic and rigorous machine learning (ML)-based framework comprised of classification, cross-validation and statistical analyses to identify the best performing classifier for breast malignancy stratification based on CEUS-derived radiomic metrics (time-intensity curve [TIC] analysis and Radiomics).

Ic. To assess the independent contribution of radiomics classifier and time-intensity curve classifier to the model accuracy in discriminating benign from malignant cases (TIC analysis versus [vs.] Radiomics).

Id. To assess the potential benefit of machine learning classifier in preventing unnecessary biopsy (TIC analysis and Radiomics).

OUTLINE:

Patients receive a contrast agent (Lumason or DEFINITY) intravenously (IV) and then undergo CEUS scan over 60-90 minutes.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Janet Jaime; Phone Number: 323-865-3205; Email: Janet.Jaime@med.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC / Norris Comprehensive Cancer Center
      • Contact: Janet Jaime; Phone Number: 323-865-3205; Email: Janet.Jaime@med.usc.edu
      • Principal Investigator: Bino A. Varghese, PhD
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Los Angeles County-USC Medical Center
      • Contact: Janet Jaime; Phone Number: 323-865-3205; Email: Janet.Jaime@med.usc.edu
      • Principal Investigator: Bino A. Varghese, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed breast masses assigned as BIRADS 4a, 4b, 4c or 5 by conventional US and recommended for ultrasound guided biopsy
• Age >= 18 years
• Female

Exclusion Criteria:

• Contraindications to microbubble contrast: Patients who have a known pulmonary hypertension and any known hypersensitivity to US contrast agent
• Women with renal failure or insufficiency (only if patient is receiving CESM scan)
• Women with Iodine contrast allergy (only if patient is receiving CESM scan)
• Women with the largest side of the mass measuring ≤ 1 cm (only if patient is receiving CEUS scan)
• Women who are pregnant, possibly pregnant, or lactating
• Women currently undergoing neoadjuvant chemotherapy
• Women < 18 years of age
• Patient ≤ 30 years (only if patient is receiving CESM scan)
• Masses in the same breast that had prior lumpectomy for cancer
• Women with cancer in the same breast will be excluded however, women with cancer in the contralateral breast will be eligible to participate in the study
• Women with an allergy to perflutren (only if patient is receiving CEUS scan)
• Prior history of biopsy for that specific lesion
• Women with breast implants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diagnostic (contrast agent, CEUS); Patients receive a contrast tracer (Lumason or DEFINITY) IV and then undergo CEUS scan over 60-90 minutes.	Procedure: Contrast-Enhanced Ultrasound; Undergo CEUS; Other Names: CEUS; Drug: Sulfur Hexafluoride Lipid Microspheres; Given IV; Other Names: Lumason; SF6 Lipid Microspheres; Sulfur Hexafluoride Lipid-type A Microspheres; Drug: Perflutren Lipid Microspheres; Given IV; Other Names: Definity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiomics-based ML-classifier framework	The performance of radiomics-based ML classifier framework will be compared to the performance of the TIC metrics. The joint performance of radiomics and TIC analysis will be compared to their individual performances. The classifier performance will be assessed using the area under curve (AUC). The Z-test will be used to compare the difference between the area under the curves 1) AUCboth versus (vs.) AUCradiomic 2) AUCboth vs. AUCTIC 3) AUCTIC vs. AUCradiomic.	Up to 12 months
Performance of radiomics-based ML approach to prevent unnecessary biopsies	Will assess the percentage of benign cases that can be classified as benign by ML (Specificity) thus been prevented from biopsy. Will select the diagnostic cut-off point based on the ROC curve constructed from the predicted probability. Such a cut-off point will result in a maximal sensitivity (100%). Specificity with 95% Clopper Pearson confidence interval will be obtained.	Up to 12 months

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Bino A Varghese, PhD, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Estimated): November 5, 2026
• Study Completion (Estimated): November 5, 2027

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Actual): December 14, 2023

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; perflutren
• Other Study ID Numbers: 1B-19-5 (Other Identifier: USC / Norris Comprehensive Cancer Center); P30CA014089 (U.S. NIH Grant/Contract); NCI-2022-03665 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No