VisR for Noninvasively Interrogating Stromal Collagen Organization as a Breast Cancer Biomarker: Evaluation of Compression in Control Subjects

NCT ID: NCT06547034

Last Updated: 2025-03-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-10-16
• Study Completion Date: 2025-02-28

Brief Summary

Purpose: The purpose of this study is to evaluate in vivo the diagnostic relevance of ultrasound-derived metrics for elasticity, viscosity, and anisotropy. To this end, we will investigate the effect of applied compression during imaging on elasticity, viscosity, and anisotropy measurements.

Participants: Twenty women with negative mammograms and no history of breast disease will be recruited. The subjects will be split into two cohorts of ten each, the first cohort aged 30-45 and the second cohort aged 46-90. Subjects will be recruited from the Breast Imaging Division of UNC Hospitals.

Procedures (methods): In this exploratory clinical study, the investigators will attempt to demonstrate that ARFI, VisR, and DDAI ultrasound measurements of elasticity, viscosity, and anisotropy in healthy breast tissue vary based on applied pre-compression. This unblinded, open-label study will be conducted in 20 women with negative mammogram results and no history of breast disease.

Detailed Description

The primary objective of breast cancer screening is to identify early stage cancer, or precancerous lesions, at a time before symptoms emerge and when treatment is likely to result in a cure. Screening is beneficial when it averts progression of disease to metastasis and/or death, but adverse effects to patients (and unnecessary medical expense) may result downstream from false positives and indiscrimination of masses that will not respond to treatment. The sensitivity of digital mammography, the current screening standard in the US, has been reported in the range of 0.40 to 0.85, with a positive predictive value of 0.31. Sensitivity is increased by augmenting mammography with MRI and B-Mode ultrasound, but false positive rates may also increase. There exists a vital need for a screening technology that exhibits high sensitivity and specificity for cancer detection with early identification of unresponsive masses.

This urgent need could be met by exploiting new imaging biomarkers. Specifically, the mechanical properties of breast tissue have been used for cancer detection, with both elasticity and viscosity demonstrated for discriminating malignant from benign lesions. Further, tissue anisotropy has been shown to correlate with core biopsy result and tumor grade, with large cancers significantly more anisotropic than small cancers. Importantly, while both MRI and ultrasound can be used to measure these biomarkers, ultrasound's cost effectiveness and ease of implementation render it an efficient platform to pursue.

The long-term goal of this research program is to develop a new ultrasound-based breast-screening tool to augment mammography. As a critical first step toward achieving this goal, the primary objective of the proposed research is to evaluate in vivo the replicability of ultrasound-derived metrics for stiffness, elasticity, viscosity, and anisotropy. These biomarkers will be measured using novel, noninvasive ultrasound technologies under development in Dr. Gallippi's laboratory: 1) Acoustic Radiation Force Impulse (ARFI) ultrasound for interrogating tissue stiffness, 2) Viscoelastic Response (VisR) ultrasound for assessing tissue elasticity and viscosity, and 3) Dynamic Displacement Anisotropy Imaging (DDAI) for measuring tissue anisotropy. These technologies have been demonstrated previously for delineating atherosclerosis, muscular dystrophy, and renal dysfunction.

The investigators hypothesize that ultrasound-derived stiffness, elasticity, viscosity, and anisotropy measurements will vary based on applied compression from the sonographer. This is because applying compression to tissue alters its organization, typically reflected by increased stiffness and viscosity and changes in mechanical anisotropy. To test this hypothesis, they will pursue the following specific aim:

Aim #1: Quantify the change in ultrasound-derived stiffness, elasticity, viscosity, and anisotropy measurements from applied pre-compression. ARFI, VisR, and DDAI imaging will be performed on breast stromal tissue in 20 women with negative mammograms and no history of breast disease. Changes in the ultrasound-derived metrics will be evaluated between no applied compression, 10% applied strain, and 25% applied strain. Additionally, magnitude of change in these metrics with applied strain will be compared between two age cohorts (aged 30-45 vs 46-90) and between breast density levels (as rated on BIRADS scale).

Conditions

Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Ages 30-45

Women ages 30-45 who have received a mammogram in the past year with negative results and have no history of breast disease.

Ultrasound

Intervention Type: DEVICE

Breast Ultrasound

Ages 46-90

Women ages 46-90 who have received a mammogram in the past year with negative results and have no history of breast disease.

Ultrasound

Intervention Type: DEVICE

Breast Ultrasound

Interventions

Ultrasound

Breast Ultrasound

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients are 30-90 years of age
• Patients have received a negative result from mammogram screening in past year
• Patients have no history of breast disease
• Informed consent obtained and signed

Exclusion Criteria

• Inability to provide informed consent
• Inability to communicate in English
• Inability to remain motionless for 15 minutes
• Any pathologies of the breast or history of breast disease
• Patients who are pregnant
• Patients who are lactating
• Patients with breast implants
• Patients with implanted cardioverters or pacemakers

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Caterina Gallippi, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University of North Carolina

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

5R01CA281150-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LCCC2411

Identifier Type: -

Identifier Source: org_study_id