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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Device: Ultrasound

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 Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Desma Jones; Phone Number: 919-843-9463; Email: desma_jones@med.unc.edu
• Study Contact Backup: Name: Caterina Gallippi, PhD; Phone Number: 9198436647; Email: cmgallip@email.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: Desma Jones; Phone Number: 984-974-8771; Email: desma_jones@med.unc.edu

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Potential study participants will be patients 20-90 years of age. In the first study arm, patients with suspicious breast lesions that are rated 4 (suspicious)or 5 (highly suggestive of malignancy) on the BI-RADS scale will be recruited. In the second study arm, patients with confirmed malignant breast lesion (s) (BI-RADS 6) who are to undergo neoadjuvant systemic therapy will be recruited. All patients will be recruited from and imaged at the University of North Carolina Hospitals. Based on local demographics, we estimate that roughly 20% will be racial and ethnic minorities. Children will not be included in this study. There will be no randomization to study arms and no intervention beyond ARFI, VisR, and DDAI ultrasound imaging.

Description

Inclusion Criteria (Arm 1):

• Subjects are 20-90 years of age
• Subjects are female
• Breast lesion is sonographically visible with B-Mode ultrasound on diagnostic workup
• Breast lesion(s) have BI-RADS 4a, 4b, 4c, or 5 rating

Exclusion Criteria (Arm 1):

• Inability to provide informed consent
• Inability to communicate in English
• Inability to remain motionless for 15 minutes
• Subjects with breast implants
• Breast mass is deeper than 4 cm from skin surface
• Subjects who are pregnant or lactating
• Subjects who have pacemakers or implanted cardioverters
• Subjects with a history of mastectomy
• Previous biopsy or surgery to the site of the mass, surgical excision of mass of interest
• Subject is male

Inclusion Criteria (Arm 2):

• Subjects are 20-90 years of age
• Subjects are female
• Breast lesion is sonographically visible with B-Mode ultrasound on diagnostic workup
• Breast lesion(s) have BI-RADS 6 rating, subject will be undergoing NAT for stage 2 or 3 malignant breast lesion(s)

Exclusion Criteria (Arm 2):

• Inability to provide informed consent
• Inability to communicate in English
• Inability to remain motionless for 15 minutes
• Subjects with breast implants
• Breast mass is deeper than 4 cm from skin surface
• Subjects who are pregnant or lactating
• Subjects who have pacemakers or implanted cardioverters
• Subjects with a history of mastectomy
• Previous biopsy or surgery to the site of the mass, surgical excision of mass of interest
• Subject is male

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women with benign breast masses; Participants in this group will be imaged once prior to biopsy, as part of the first study arm	Device: Ultrasound; Non-invasive breast imaging using VisR ultrasound
Women with malignant breast masses; Participants in this group will be imaged once prior to biopsy, as part of the first study arm	Device: Ultrasound; Non-invasive breast imaging using VisR ultrasound
Women undergoing neoadjuvant systemic therapy (NAT); Participants in this group will be imaged once before starting NAT, once approximately midway through NAT, and once after completion of NAT, as part of the second study arm	Device: Ultrasound; Non-invasive breast imaging using VisR ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ARFI Peak Displacement (PD) in lesion (Study Arm 1)	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.	Baseline imaging
ARFI Peak Displacement (PD) in surrounding tissue (Study Arm 1)	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.	Baseline imaging
VisR Relative Elasticity (RE) in lesion (Study Arm 1)	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.	Baseline imaging
VisR Relative Elasticity (RE) in surrounding tissue (Study Arm 1)	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.	Baseline imaging
VisR Relative Viscosity (RV) in lesion (Study Arm 1)	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.	Baseline imaging
VisR Relative Viscosity (RV) in surrounding tissue (Study Arm 1)	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.	Baseline imaging
ARFI PD DoA in lesion (Study Arm 1)	Ratio of maximum to minimum (DoA) of ARFI PD inside the lesion over four imaging angles	Baseline imaging
ARFI PD DoA in surrounding tissue (Study Arm 1)	Ratio of maximum to minimum (DoA) of ARFI PD in an area of tissue outside of the lesion over four imaging angles	Baseline imaging
VisR RE DoA in lesion (Study Arm 1)	Ratio of maximum to minimum (DoA) of VisR RE inside the lesion over four imaging angles	Baseline imaging
VisR RE DoA in surrounding tissue (Study Arm 1)	Ratio of maximum to minimum (DoA) of VisR RE in an area of tissue outside of the lesion over four imaging angles	Baseline imaging
VisR RV DoA in lesion (Study Arm 1)	Ratio of maximum to minimum (DoA) of VisR RV inside the lesion over four imaging angles	Baseline imaging
VisR RV DoA in surrounding tissue (Study Arm 1)	Ratio of maximum to minimum (DoA) of VisR RV in an area of tissue outside of the lesion over four imaging angles	Baseline imaging
ARFI Peak Displacement (PD) in lesion (Study Arm 2)	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.	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
ARFI Peak Displacement (PD) in surrounding tissue (Study Arm 2)	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.	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
VisR Relative Elasticity (RE) in lesion (Study Arm 2)	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.	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
VisR Relative Elasticity (RE) in surrounding tissue (Study Arm 2)	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.	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
VisR Relative Viscosity (RV) in lesion (Study Arm 2)	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.	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
VisR Relative Viscosity (RV) in surrounding tissue (Study Arm 2)	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.	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
ARFI PD DoA in lesion (Study Arm 2)	Ratio of maximum to minimum (DoA) of ARFI PD inside the lesion over four imaging angles	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
ARFI PD DoA in surrounding tissue (Study Arm 2)	Ratio of maximum to minimum (DoA) of ARFI PD in an area of tissue outside of the lesion over four imaging angles	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
VisR RE DoA in lesion (Study Arm 2)	Ratio of maximum to minimum (DoA) of VisR RE inside the lesion over four imaging angles	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
VisR RE DoA in surrounding tissue (Study Arm 2)	Ratio of maximum to minimum (DoA) of VisR RE in an area of tissue outside of the lesion over four imaging angles	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
VisR RV DoA in lesion (Study Arm 2)	Ratio of maximum to minimum (DoA) of VisR RV inside the lesion over four imaging angles	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months
VisR RV DoA in surrounding tissue (Study Arm 2)	Ratio of maximum to minimum (DoA) of VisR RV in an area of tissue outside of the lesion over four imaging angles	From enrollment to end of neoadjuvant systemic therapy, assessed up to 8 months

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Caterina Gallippi, PhD, Lampe Joint Department of Biomedical Engineering

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2025
• Primary Completion (Estimated): August 25, 2027
• Study Completion (Estimated): February 24, 2028

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 12, 2025
• First Posted (Actual): March 17, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer; Neoadjuvant chemotherapy; Ultrasound elastography; Elasticity; Viscosity; Non-invasive imaging; Breast cancer diagnosis; Ultrasound screening; ARFI Ultrasound; VisR Ultrasound; Malignant breast lesion; Benign breast lesion; Tissue anisotropy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Ultrasonography
• Other Study ID Numbers: LCCC2449; 5R01CA281150-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: 9 to 36 months following publication
• IPD Sharing Access Criteria: The investigator who proposes to use the data has approval from an IRB, IEC, or REB, as applicable, and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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