VisR Ultrasound for Noninvasively Interrogating Stromal Collagen Organization in Women as a Breast Cancer Biomarker: Evaluation of Anisotropy in Cancer Patients

Recruiting

• Conditions: Breast Cancer

• Registration Number: NCT06878547
• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Brief Summary

Purpose: This study will evaluate how measurements of tissue stiffness, viscosity, and anisotropy using non-invasive ultrasound imaging correlate with breast tumor malignancy and response to chemotherapy.

Participants: Up to 200 women with benign or malignant breast tumors for arm 1 and up to 50 women undergoing neoadjuvant chemotherapy in the breast for arm 2 will be recruited.

Procedures (methods): The research team will use an ultrasound scanner to acquire non-invasive elastography data from the breast of each subject, testing a range of transducer rotation angles. Transducer position will be monitored using a position sensor during imaging.

Detailed Description

The purpose of the proposed research is to evaluate in vivo the feasibility of ultrasound-derived metrics for stiffness, elasticity, viscosity, and anisotropy for clinical diagnostic breast imaging. 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. This proposed pilot study has two unblinded arms, corresponding to two aims from our NIH R01 grant.

The hypothesis of this study is that ultrasound-derived stiffness, elasticity, viscosity, and anisotropy measured in breast tissue will differ between patients with malignant and benign lesions, and between patients who are responsive versus non-responsive to neoadjuvant systemic therapy (NAT). To test these hypotheses, the research team will pursue the following specific aims from the R01 grant (specific aim #1 is being addressed by a different ongoing study, IRB #24-0122):

Aim #2: Correlate in vivo VisR outcomes to collagen fiber organization in malignant and benign breast masses and surrounding stroma in women, and demonstrate the clinical relevance of such to cancer diagnosis and staging. ARFI, VisR, and DDAI imaging will be performed on women with malignant or benign breast tumors to determine their diagnostic value in predicting malignancy. Results will be compared with histological assessment of collagen fiber organization.

Aim #3: Correlate in vivo VisR outcomes to pre- and post-NAT collagen fiber organization, and demonstrate the clinical relevance of such to predicting pathologic complete response (pCR) to NAT in women. ARFI, VisR, and DDAI imaging will be performed on women with malignant breast tumors undergoing neoadjuvant systemic therapy to monitor changes in mechanical properties during treatment and predict response to chemotherapy from early timepoints. Results will be compared with histological assessment of collagen fiber organization.

Study Timeline

• Study First Submitted: 2025-03-03
• Study Start: 2025-03-07
• Study First Submitted QC: 2025-03-12
• Study First Posted: 2025-03-17
• Status Verified: 2025-04
• Last Update Submitted: 2025-05-27
• Last Update Posted: 2025-05-28
• Primary Completion: 2027-08-25
• Study Completion: 2028-02-24

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 250

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
ARFI Peak Displacement (PD) in lesion (Study Arm 1)	Baseline imaging	Average ARFI Peak Displacement (PD) value inside of lesion. Peak Displacement (PD) - Maximum displacement of tissue in the breast after an Acoustic Radiation Force Impulse (ARFI) excitation.
ARFI Peak Displacement (PD) in surrounding tissue (Study Arm 1)	Baseline imaging	Average ARFI Peak Displacement (PD) value in an area of breast tissue outside of lesion. Peak Displacement (PD) - Maximum displacement of tissue in the breast after an Acoustic Radiation Force Impulse (ARFI) excitation.
VisR Relative Elasticity (RE) in lesion (Study Arm 1)	Baseline imaging	Average VisR RE value in lesion. RE - relative elasticity (relative to force applied) of breast tissue measured using a Viscoelastic Response (VisR) ultrasound imaging sequence.
VisR Relative Elasticity (RE) in surrounding tissue (Study Arm 1)	Baseline imaging	Average VisR RE value in area of tissue outside of the lesion. RE - relative elasticity (relative to force applied) of breast tissue measured using a Viscoelastic Response (VisR) ultrasound imaging sequence.
VisR Relative Viscosity (RV) in lesion (Study Arm 1)	Baseline imaging	Average VisR RV value in lesion. RV - relative viscosity (relative to force applied) of breast tissue measured using a Viscoelastic Response (VisR) ultrasound imaging sequence.
VisR Relative Viscosity (RV) in surrounding tissue (Study Arm 1)	Baseline imaging	Average VisR RV value in area of tissue outside of the lesion. RV - relative viscosity (relative to force applied) of breast tissue measured using a Viscoelastic Response (VisR) ultrasound imaging sequence.
ARFI PD DoA in lesion (Study Arm 1)	Baseline imaging	Ratio of maximum to minimum (DoA) of ARFI PD inside the lesion over four imaging angles
ARFI PD DoA in surrounding tissue (Study Arm 1)	Baseline imaging	Ratio of maximum to minimum (DoA) of ARFI PD in an area of tissue outside of the lesion over four imaging angles
VisR RE DoA in lesion (Study Arm 1)	Baseline imaging	Ratio of maximum to minimum (DoA) of VisR RE inside the lesion over four imaging angles
VisR RE DoA in surrounding tissue (Study Arm 1)	Baseline imaging	Ratio of maximum to minimum (DoA) of VisR RE in an area of tissue outside of the lesion over four imaging angles
VisR RV DoA in lesion (Study Arm 1)	Baseline imaging	Ratio of maximum to minimum (DoA) of VisR RV inside the lesion over four imaging angles
VisR RV DoA in surrounding tissue (Study Arm 1)	Baseline imaging	Ratio of maximum to minimum (DoA) of VisR RV in an area of tissue outside of the lesion over four imaging angles
ARFI Peak Displacement (PD) in lesion (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Average ARFI Peak Displacement (PD) value inside of lesion. Peak Displacement (PD) - Maximum displacement of tissue in the breast after an Acoustic Radiation Force Impulse (ARFI) excitation.
ARFI Peak Displacement (PD) in surrounding tissue (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Average ARFI Peak Displacement (PD) value in an area of breast tissue outside of lesion. Peak Displacement (PD) - Maximum displacement of tissue in the breast after an Acoustic Radiation Force Impulse (ARFI) excitation.
VisR Relative Elasticity (RE) in lesion (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Average VisR RE value in lesion. RE - relative elasticity (relative to force applied) of breast tissue measured using a Viscoelastic Response (VisR) ultrasound imaging sequence.
VisR Relative Elasticity (RE) in surrounding tissue (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Average VisR RE value in area of tissue outside of the lesion. RE - relative elasticity (relative to force applied) of breast tissue measured using a Viscoelastic Response (VisR) ultrasound imaging sequence.
VisR Relative Viscosity (RV) in lesion (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Average VisR RV value in lesion. RV - relative viscosity (relative to force applied) of breast tissue measured using a Viscoelastic Response (VisR) ultrasound imaging sequence.
VisR Relative Viscosity (RV) in surrounding tissue (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Average VisR RV value in area of tissue outside of the lesion. RV - relative viscosity (relative to force applied) of breast tissue measured using a Viscoelastic Response (VisR) ultrasound imaging sequence.
ARFI PD DoA in lesion (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Ratio of maximum to minimum (DoA) of ARFI PD inside the lesion over four imaging angles
ARFI PD DoA in surrounding tissue (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Ratio of maximum to minimum (DoA) of ARFI PD in an area of tissue outside of the lesion over four imaging angles
VisR RE DoA in lesion (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Ratio of maximum to minimum (DoA) of VisR RE inside the lesion over four imaging angles
VisR RE DoA in surrounding tissue (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Ratio of maximum to minimum (DoA) of VisR RE in an area of tissue outside of the lesion over four imaging angles
VisR RV DoA in lesion (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Ratio of maximum to minimum (DoA) of VisR RV inside the lesion over four imaging angles
VisR RV DoA in surrounding tissue (Study Arm 2)	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months	Ratio of maximum to minimum (DoA) of VisR RV in an area of tissue outside of the lesion over four imaging angles

Trial Locations

Locations (1)

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States