Trial Outcomes & Findings for ARFI, VisR and DDAI Ultrasound for Improving Discrimination of Malignant and Unresponsive Breast Cancer (NCT NCT03785782)

NCT ID: NCT03785782

Last Updated: 2025-02-20

Results Overview

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate peak displacement (PD) and correlated with biopsy findings of malignant or benign. Peak Displacement (PD) - Maximum displacement of tissue in the breast lesion after an Acoustic Radiation Force Impulse (ARFI) excitation. Participants who have undergone breast ultrasonogram were categorized as BIRADS-4a, 4b, 4c, or -5 masses.

• Recruitment status: COMPLETED
• Target enrollment: 45 participants
• Primary outcome timeframe: Baseline imaging
• Results posted on: 2025-02-20

Participant Flow

Participant milestones

Measure	Women Scheduled for Biopsy Participants who have undergone breast ultrasonogram, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis.	Women Scheduled for Neoadjuvant Chemo Participants who have undergone breast ultrasonogram, malignant breast tumor was confirmed with biopsy and scheduled to receive neoadjuvant chemotherapy.
Overall Study STARTED	40	5
Overall Study COMPLETED	34	4
Overall Study NOT COMPLETED	6	1

Reasons for withdrawal

Measure	Women Scheduled for Biopsy Participants who have undergone breast ultrasonogram, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis.	Women Scheduled for Neoadjuvant Chemo Participants who have undergone breast ultrasonogram, malignant breast tumor was confirmed with biopsy and scheduled to receive neoadjuvant chemotherapy.
Overall Study their lesions' were not suitable for the study criteria	2	0
Overall Study Withdrawal by Subject	1	1
Overall Study insufficient image quality.	3	0

Baseline Characteristics

ARFI, VisR and DDAI Ultrasound for Improving Discrimination of Malignant and Unresponsive Breast Cancer

Baseline characteristics by cohort

Measure	Women Scheduled for Biopsy n=39 Participants Participants who have undergone breast ultrasonogram, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis.	Women Scheduled for Neoadjuvant Chemo n=5 Participants Participants who have undergone breast ultrasonogram, malignant breast tumor was confirmed with biopsy and scheduled to receive neoadjuvant chemotherapy.	Total n=44 Participants Total of all reporting groups
Age, Continuous	53.0 years STANDARD_DEVIATION 14.0 • n=5 Participants	54.4 years STANDARD_DEVIATION 15.7 • n=7 Participants	53.2 years STANDARD_DEVIATION 14.0 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	5 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	4 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	3 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	39 participants n=5 Participants	5 participants n=7 Participants	44 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline imaging

Population: In total 34 subjects were included in the analysis. Six subjects were excluded because their lessons were unsuitable for the study criteria, had insufficient image quality, or were withdrawn. Biopsy finding of malignant:12 participants, Biopsy finding of benign: 22 participants. Women scheduled for neoadjuvant chemo are not included since they already have a malignant disease diagnosis.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate peak displacement (PD) and correlated with biopsy findings of malignant or benign.

Peak Displacement (PD) - Maximum displacement of tissue in the breast lesion after an Acoustic Radiation Force Impulse (ARFI) excitation.

Participants who have undergone breast ultrasonogram were categorized as BIRADS-4a, 4b, 4c, or -5 masses.

Outcome measures

Measure	Biopsy Finding of Malignant n=12 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=22 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Correlation of Peak Displacement (PD) for Detecting Malignancy	4.5803 microns Standard Error 2.9947	8.628 microns Standard Error 7.8776	—	—

PRIMARY outcome

Timeframe: Up to 8 months

Population: Only women scheduled for neoadjuvant chemo and completed imaging (in total 4 subjects) were included in the analysis. One subject was withdrawn and was excluded from the analysis. Women scheduled for biopsy were not included.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate peak displacement (PD) and correlated with biopsy findings of malignant or benign. Participants were imaged at baseline and end of each chemotherapy cycle. Patients were imaged 3-8 times w/ 3-4 weeks between scans.

Peak Displacement (PD) - Maximum displacement of tissue in the breast lesion after an Acoustic Radiation Force Impulse (ARFI) excitation.

Outcome measures

Measure	Biopsy Finding of Malignant n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Weighted Correlation Between Peak Displacement (PD) to Predict Response to Neoadjuvant Chemotherapy. Responder to chemo	2.4715 microns Standard Error 1.4746	6.7281 microns Standard Error 3.5461	—	—
Weighted Correlation Between Peak Displacement (PD) to Predict Response to Neoadjuvant Chemotherapy. Non-responders to chemo	2.5268 microns Standard Error 1.3869	3.2511 microns Standard Error 1.3869	—	—

PRIMARY outcome

Timeframe: Up to 8 months

Population: Only women scheduled for neoadjuvant chemo and completed imaging (in total 4 subjects) were included in the analysis. One subject was withdrawn and was excluded from the analysis. Women scheduled for biopsy were not included.

The ultrasound data was processed to calculate displacement at a given time (TD) for ARFI and statistically correlated to response of treatment with neoadjuvant chemotherapy. These values were weighted based on the number of imaging visits during subjects' treatment. Acoustic Radiation Force Impulse (ARFI) - Ultrasound imaging technique in which a sacoustic pulse is transmitted into tissue, causing it to displace and recover in <1 ms. The tissue displacement was used to estimate stiffness and viscosity. Response to chemo - Defined as the lesion shrinking by 25% or more over the course of chemotherapy. Non-responders to chemo - Defined as lesion not shrinking by 25% or more over the course of chemotherapy. Participants were imaged at baseline and end of each chemotherapy cycle. Patients were imaged 3-8 times w/ 3-4 weeks between scans.

Outcome measures

Measure	Biopsy Finding of Malignant n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Weighted Correlation Between Displacement at a Given Time (TD) for ARFI to Predict Response to Neoadjuvant Chemotherapy Responder to chemo	2.3495 microns Standard Error 1.3904	6.1222 microns Standard Error 3.0388	—	—
Weighted Correlation Between Displacement at a Given Time (TD) for ARFI to Predict Response to Neoadjuvant Chemotherapy Non-responders to chemo	2.2757 microns Standard Error 1.1146	3.0156 microns Standard Error 1.2928	—	—

PRIMARY outcome

Timeframe: Up to 8 months

Population: Only women scheduled for neoadjuvant chemo and completed imaging (in total 4 subjects) were included in the analysis. One subject was withdrawn and was excluded from the analysis. Women scheduled for biopsy were not included.

The ultrasound data will be processed to calculate relative elasticity (RE) and statistically correlated to response of treatment with neoadjuvant chemotherapy. These values were weighted based on the number of imaging visits during subjects' treatment. Relative Elasticity (RE) - Qualitative estimate for tissue stiffness in the breast lesion based on VisR imaging. Response to chemo - Defined as the lesion shrinking by 25% or more over the course of chemotherapy. Non-responders to chemo - Defined as lesion not shrinking by 25% or more over the course of chemotherapy. Participants were imaged at baseline and end of each chemotherapy cycle. Patients were imaged 3-8 times w/ 3-4 weeks between scans.

Outcome measures

Measure	Biopsy Finding of Malignant n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Weighted Correlation Between Relative Elasticity (RE) to Predict Response to Neoadjuvant Chemotherapy. Responder to chemo	177.69 1/millimeter Standard Error 69.91	89.41 1/millimeter Standard Error 87.51	—	—
Weighted Correlation Between Relative Elasticity (RE) to Predict Response to Neoadjuvant Chemotherapy. Non-responders to chemo	190.51 1/millimeter Standard Error 43.58	164.42 1/millimeter Standard Error 87.51	—	—

PRIMARY outcome

Timeframe: Up to 8 months

Population: Only women scheduled for neoadjuvant chemo and completed imaging (in total 4 subjects) were included in the analysis. One subject was withdrawn and was excluded from the analysis. Women scheduled for biopsy were not included.

The ultrasound data will be processed to calculate relative viscosity (RV) and statistically correlated to response of treatment with neoadjuvant chemotherapy. These values were weighted based on the number of imaging visits during subjects' treatment. Relative Viscosity (RV) - Qualitative estimate for tissue viscosity in the breast lesion based on VisR imaging. Response to chemo - Defined as the lesion shrinking by 25% or more over the course of chemotherapy. Non-responders to chemo - Defined as lesions not shrinking by 25% or more over the course of chemotherapy. Participants were imaged at baseline and end of each chemotherapy cycle. Patients were imaged 3-8 times w/ 3-4 weeks between scans.

Outcome measures

Measure	Biopsy Finding of Malignant n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Weighted Correlation Between Relative Viscosity (RV) to Predict Response to Neoadjuvant Chemotherapy. Responder to chemo	384.55 milli second /millimeter Standard Error 207.70	164.12 milli second /millimeter Standard Error 85.79	—	—
Weighted Correlation Between Relative Viscosity (RV) to Predict Response to Neoadjuvant Chemotherapy. Non-responders to chemo	362.58 milli second /millimeter Standard Error 179.51	281.54 milli second /millimeter Standard Error 100.05	—	—

PRIMARY outcome

Timeframe: Up to 8 months

Population: Only women scheduled for neoadjuvant chemo and completed imaging (in total 4 subjects) were included in the analysis. One subject was withdrawn and was excluded from the analysis. Women scheduled for biopsy were not included.

The ultrasound data will be processed to calculate tissue mass (TM) for VisR and statistically correlated to the response of treatment with neoadjuvant chemotherapy. These values were weighted based on the number of imaging visits during subjects' treatment. Tissue Mass (TM) - Qualitative estimate for tissue mass in the breast lesion based on VisR imaging. Viscoelastic Response (VisR) - Ultrasound imaging technique in which a strong acoustic pulse is transmitted into the tissue, causing it to displace and recover. The tissue recovery curve is then fit to a mass-spring-damper physics model to estimate stiffness and viscosity. Response to chemo - Defined as the lesion shrinking by 25% or more over the course of chemotherapy. Non-responders to chemo - Defined as lesions not shrinking by 25% or more over the course of chemotherapy. Participants were imaged at baseline and end of each chemotherapy cycle. Patients were imaged 3-8 times w/ 3-4 weeks between scans.

Outcome measures

Measure	Biopsy Finding of Malignant n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Weighted Correlation Between Tissue Mass (TM) for VisR to Predict Response to Neoadjuvant Chemotherapy. Responder to chemo	0.02 Kg/m Standard Error 0.02	0.05 Kg/m Standard Error 0.02	—	—
Weighted Correlation Between Tissue Mass (TM) for VisR to Predict Response to Neoadjuvant Chemotherapy. Non-responders to chemo	0.03 Kg/m Standard Error 0.01	0.05 Kg/m Standard Error 0.03	—	—

PRIMARY outcome

Timeframe: Up to 8 months

Population: Only women scheduled for neoadjuvant chemo and completed imaging (in total 4 subjects) were included in the analysis. One subject was withdrawn and was excluded from the analysis. Women scheduled for biopsy were not included.

The ultrasound data will be processed to calculate the ratio of ARFI PD values at 90o versus 0 o transducer orientations for DDAI and statistically correlated to the response of treatment with neoadjuvant chemotherapy. These values were weighted based on the number of imaging visits during subjects' treatment. Acoustic Radiation Force Impulse (ARFI) - Ultrasound imaging technique in which a strong acoustic pulse is transmitted into the tissue, causing it to displace and recover in less than a millisecond. The tissue displacement can be tracked and used to estimate stiffness and viscosity. Peak Displacement (PD) - Maximum displacement of tissue in the breast lesion after an ARFI excitation. Response to chemo - Defined as the lesion shrinking by 25% or more over the course of chemotherapy. Non-responders to chemo - Defined as lesions not shrinking by 25% or more. Participants were imaged at baseline and end of each chemotherapy cycle. Patients were imaged 3-8 times w/ 3-4 weeks btwn.

Outcome measures

Measure	Biopsy Finding of Malignant n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees n=4 Participants ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree n=4 Participants ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Comparison of ARFI PD Values at 90o Versus 0o Transducer Orientations for DDAI to Predict Response to Neoadjuvant Chemotherapy. Responder to chemo	3.56 unitless ratio Standard Error 3.08	2.11 unitless ratio Standard Error 1.29	7.99 unitless ratio Standard Error 5.80	6.06 unitless ratio Standard Error 4.27
Comparison of ARFI PD Values at 90o Versus 0o Transducer Orientations for DDAI to Predict Response to Neoadjuvant Chemotherapy. Non-responders to chemo	2.52 unitless ratio Standard Error 1.13	2.11 unitless ratio Standard Error 1.29	7.99 unitless ratio Standard Error 5.80	2.68 unitless ratio Standard Error 0.10

PRIMARY outcome

Timeframe: Up to 60 days

Population: Only women scheduled for neoadjuvant chemo and completed imaging (in total 4 subjects) were included in the analysis. One subject was withdrawn and was excluded from the analysis. Women scheduled for biopsy were not included.

The ultrasound data was processed to calculate ratio of VisR RE values at 90o versus 0o transducer orientations for DDAI and statistically correlated to response of treatment with neoadjuvant chemotherapy. Values were weighted based on the number of imaging visits during subjects' treatment. Participants were imaged at baseline and end of each chemo cycle. Patients were imaged 3-8 times w/ 3-4 weeks btwn scans.

Viscoelastic Response (VisR) - Ultrasound technique in which an acoustic pulse is transmitted into the tissue, causing it to displace and recover. Tissue recovery is fit to a mass-spring-damper physics model to estimate stiffness and viscosity.

Relative Elasticity (RE) - Qualitative estimate for tissue stiffness in the breast lesion based on VisR imaging.

Response to chemo - Defined as the lesion shrinking by 25% or more over the course of chemotherapy.

Non-responders to chemo - Defined as lesions not shrinking by 25% or more over the course of chemotherapy.

Outcome measures

Measure	Biopsy Finding of Malignant n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees n=4 Participants ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree n=4 Participants ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Comparison of Ratio of ARFI PD Values at 90o Versus 0o Transducer Orientations for DDAI to Predict Response to Neoadjuvant Chemotherapy. Responder to chemo	155.59 unitless ratio Standard Error 164.03	170.15 unitless ratio Standard Error 8.74	69.45 unitless ratio Standard Error 33.08	107.00 unitless ratio Standard Error 81.34
Comparison of Ratio of ARFI PD Values at 90o Versus 0o Transducer Orientations for DDAI to Predict Response to Neoadjuvant Chemotherapy. Non-responders to chemo	179.02 unitless ratio Standard Error 1.84	185.64 unitless ratio Standard Error 83.47	172.82 unitless ratio Standard Error 153.11	160.95 unitless ratio Standard Error 16.97

PRIMARY outcome

Timeframe: Up to 8 months

Population: Only women scheduled for neoadjuvant chemo and completed imaging (in total 4 subjects) were included in the analysis. One subject was withdrawn and was excluded from the analysis. Women scheduled for biopsy were not included.

The ultrasound data will be processed to calculate ratio of RV values at 90o versus 0o transducer orientations for DDAI and statistically correlated to response of treatment with neoadjuvant chemotherapy. These values were weighted based on the number of imaging visits during subjects' treatment. Participants were imaged at baseline and end of each chemotherapy cycle. Patients were imaged 3-8 times w/ 3-4 weeks between scans.

Relative Viscosity (RV) - Qualitative estimate for tissue viscosity in the breast lesion based on VisR imaging.

Response to chemo - Defined as the lesion shrinking by 25% or more over the course of chemotherapy.

Non-responders to chemo - Defined as lesion not shrinking by 25% or more over the course of chemotherapy.

Outcome measures

Measure	Biopsy Finding of Malignant n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=4 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees n=4 Participants ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree n=4 Participants ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Weighted Correlation Between Ratio of RV Values at 90o Versus 0o Transducer Orientations for DDAI to Predict Response to Neoadjuvant Chemotherapy. Responder to chemo	289.93 unitless ratio Standard Error 353.30	386.65 unitless ratio Standard Error 288.47	144.27 unitless ratio Standard Error 115.12	191.86 unitless ratio Standard Error 100.15
Weighted Correlation Between Ratio of RV Values at 90o Versus 0o Transducer Orientations for DDAI to Predict Response to Neoadjuvant Chemotherapy. Non-responders to chemo	322.84 unitless ratio Standard Error 159.66	332.70 unitless ratio Standard Error 241.89	231.17 unitless ratio Standard Error 103.83	336.71 unitless ratio Standard Error 52.55

PRIMARY outcome

Timeframe: Baseline

Population: In total 34 subjects were included in the analysis. Six subjects were excluded because their lessons were unsuitable for the study criteria, had insufficient image quality, or were withdrawn. Biopsy finding of malignant:12 participants, Biopsy finding of benign: 22 participants. Women scheduled for neoadjuvant chemo are not included since they already have a malignant disease diagnosis.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate displacement at a given time (TD) for ARFI and correlated with biopsy findings of malignant or benign.

Acoustic Radiation Force Impulse (ARFI) - Ultrasound imaging technique in which a strong acoustic pulse is transmitted into tissue, causing it to displace and recover in less than a millisecond. The tissue displacement can be tracked and used to estimate stiffness and viscosity.

Participants were imaged at baseline.

Outcome measures

Measure	Biopsy Finding of Malignant n=12 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=22 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Correlation of Displacement at a Given Time (TD) for Detecting Malignancy.	4.16 microns Standard Error 2.76	7.15 microns Standard Error 5.54	—	—

PRIMARY outcome

Timeframe: Baseline

Population: In total 34 subjects were included in the analysis. Six subjects were excluded because their lessons were unsuitable for the study criteria, had insufficient image quality, or were withdrawn. Biopsy finding of malignant:12 participants, Biopsy finding of benign: 22 participants. Women scheduled for neoadjuvant chemo are not included since they already have a malignant disease diagnosis.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate relative elasticity (RE) and correlated with biopsy finding of malignant or benign.

Relative Elasticity (RE) - Qualitative estimate for tissue stiffness in the breast lesion based on VisR imaging.

Outcome measures

Measure	Biopsy Finding of Malignant n=12 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=22 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Correlation of Relative Elasticity (RE) for Detecting Malignancy.	125.59 1/millimeter Standard Error 69.69	89.88 1/millimeter Standard Error 76.04	—	—

PRIMARY outcome

Timeframe: Baseline

Population: In total 34 subjects were included in the analysis. Six subjects were excluded because their lessons were unsuitable for the study criteria, had insufficient image quality, or were withdrawn. Biopsy finding of malignant:12 participants, Biopsy finding of benign: 22 participants. Women scheduled for neoadjuvant chemo are not included since they already have a malignant disease diagnosis.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate relative viscosity (RV) and correlated with biopsy findings of malignant or benign.

Relative Viscosity (RV) - Qualitative estimate for tissue viscosity in the breast lesion based on VisR imaging. Participants were imaged according to their neoadjuvant chemotherapy schedule, at baseline and end of each chemotherapy type

Outcome measures

Measure	Biopsy Finding of Malignant n=12 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=22 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Correlation of Relative Viscosity (RV) for Detecting Malignancy.	194.43 s/m Standard Error 170.13	137.60 s/m Standard Error 116.95	—	—

PRIMARY outcome

Timeframe: Baseline

Population: In total 34 subjects were included in the analysis. Six subjects were excluded because their lessons were unsuitable for the study criteria, had insufficient image quality, or were withdrawn. Biopsy finding of malignant:12 participants, Biopsy finding of benign: 22 participants. Women scheduled for neoadjuvant chemo are not included since they already have a malignant disease diagnosis.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate tissue mass (TM) for VisRand correlated with biopsy findings of malignant or benign. Participants were imaged according to their neoadjuvant chemotherapy schedule, at baseline and end of each chemotherapy type Viscoelastic Response (VisR) - Ultrasound imaging technique in which a strong acoustic pulse is transmitted into the tissue, causing it to displace and recover. The tissue recovery curve is then fit to a mass-spring-damper physics model to estimate stiffness and viscosity.

Outcome measures

Measure	Biopsy Finding of Malignant n=12 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=22 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Correlation of Tissue Mass (TM) for VisR for Detecting Malignancy	0.46 Kg/m Standard Error 0.50	0.34 Kg/m Standard Error 0.31	—	—

PRIMARY outcome

Timeframe: Baseline

Population: In total 34 subjects were included in the analysis. Six subjects were excluded because their lessons were unsuitable for the study criteria, had insufficient image quality, or were withdrawn. Biopsy finding of malignant:12 participants, Biopsy finding of benign: 22 participants. Women scheduled for neoadjuvant chemo are not included since they already have a malignant disease diagnosis.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate ratio of ARFI PD values at 90o versus 0o transducer orientations for DDAI and correlated with biopsy findings of malignant or benign. Participants were imaged according to their neoadjuvant chemotherapy schedule, at baseline and end of each chemotherapy type Acoustic Radiation Force Impulse (ARFI) - Ultrasound imaging technique in which a strong acoustic pulse is transmitted into the tissue, causing it to displace and recover in less than a millisecond. The tissue displacement can be tracked and used to estimate stiffness and viscosity.

Peak Displacement (PD) - Maximum displacement of tissue in the breast lesion after an ARFI excitation.

Outcome measures

Measure	Biopsy Finding of Malignant n=34 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=34 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Correlation of Ratio of ARFI PD Values at 90o Versus 0o Transducer Orientations for Detecting Malignancy. Biopsy finding of malignant	4.88 unitless ratio Standard Error 3.40	4.30 unitless ratio Standard Error 2.45	—	—
Correlation of Ratio of ARFI PD Values at 90o Versus 0o Transducer Orientations for Detecting Malignancy. Biopsy finding of benign	9.84 unitless ratio Standard Error 8.31	8.10 unitless ratio Standard Error 7.34	—	—

PRIMARY outcome

Timeframe: Baseline

Population: In total 34 subjects were included in the analysis. Six subjects were excluded because their lessons were unsuitable for the study criteria, had insufficient image quality, or were withdrawn. Biopsy finding of malignant:12 participants, Biopsy finding of benign: 22 participants. Women scheduled for neoadjuvant chemo are not included since they already have a malignant disease diagnosis.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate the ratio of VisR RE values at 90o versus 0o transducer orientations for DDAI and correlated with biopsy findings of malignant or benign. Participants were imaged according to their neoadjuvant chemotherapy schedule, at baseline and end of each chemotherapy type Viscoelastic Response (VisR) - Ultrasound imaging technique in which a strong acoustic pulse is transmitted into the tissue, causing it to displace and recover. The tissue recovery curve is then fit to a mass-spring-damper physics model to estimate stiffness and viscosity.

Relative Elasticity (RE) - Qualitative estimate for tissue stiffness in the breast lesion based on VisR imaging.

Outcome measures

Measure	Biopsy Finding of Malignant n=34 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=34 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Correlation of Ratio of VisR RE Values at 90o Versus 0o Transducer Orientations for Detecting Malignancy. Biopsy finding of malignant	139.66 unitless ratio Standard Error 100.61	117.26 unitless ratio Standard Error 70.72	—	—
Correlation of Ratio of VisR RE Values at 90o Versus 0o Transducer Orientations for Detecting Malignancy. Biopsy finding of benign	77.47 unitless ratio Standard Error 62.73	84.06 unitless ratio Standard Error 74.92	—	—

PRIMARY outcome

Timeframe: Baseline

Population: In total 34 subjects were included in the analysis. Six subjects were excluded because their lessons were unsuitable for the study criteria, had insufficient image quality, or were withdrawn. Biopsy finding of malignant:12 participants, Biopsy finding of benign: 22 participants. Women scheduled for neoadjuvant chemo are not included since they already have a malignant disease diagnosis.

The correlation of each ultrasound metric will be analyzed by constructing separate receiver operating characteristic (ROC) curves. The ultrasound data were processed to calculate ratio of VisR RV values at 90o versus 0o transducer orientations for DDAI and correlated with biopsy findings of malignant or benign. Participants were imaged according to their neoadjuvant chemotherapy schedule, at baseline and end of each chemotherapy type Displacement at Time (TD) - Displacement of tissue in the breast lesion at time t=0.2 ms after an ARFI excitation.

Viscoelastic Response (VisR) - Ultrasound imaging technique in which a strong acoustic pulse is transmitted into tissue, causing it to displace and recover. The tissue recovery curve is then fit to a mass-spring-damper physics model to estimate stiffness and viscosity.

Relative Viscosity (RV) - Qualitative estimate for tissue viscosity in the breast lesion based on VisR imaging.

Outcome measures

Measure	Biopsy Finding of Malignant n=34 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was confirmed.	Biopsy Finding of Benign n=34 Participants Participants who have undergone breast ultrasonograms, categorized BIRADS-4a, 4b, 4c, or -5 masses requiring biopsy for the disease diagnosis. A biopsy was performed and cancer was not found.	ARFI PD After Neoadjuvant Chemo 90 Degrees ARFI PD measured at 90 degrees transducer angle after neoadjuvant chemotherapy	ARFI PD After Neoadjuvant Chemo 0 Degree ARFI PD measured at 0 degree transducer angle after neoadjuvant chemotherapy
Correlation of Ratio of VisR RV Values at 90o Versus 0o Transducer Orientations for Detecting Malignancy. Biopsy finding of malignant	161.10 unitless ratio Standard Error 149.28	205.46 unitless ratio Standard Error 132.67	—	—
Correlation of Ratio of VisR RV Values at 90o Versus 0o Transducer Orientations for Detecting Malignancy. Biopsy finding of benign	113.67 unitless ratio Standard Error 84.38	157.49 unitless ratio Standard Error 142.23	—	—

Adverse Events

Women Scheduled for Biopsy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Women Scheduled for Neoadjuvant Chemo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Director, Clinical Research, Department of Radiology

University of North Carolina at Chapel Hill

Phone: 919-966-4997

Email: rad_research@med.unc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place