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

UNC Lineberger Comprehensive Cancer Center250 enrolled

Overview

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.

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.

Eligibility

Sex: FEMALEMin age: 20 YearsMax age: 90 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.