Signs and Symptoms
Conditions
Keywords
ultrasound, breast, angiography
Brief summary
Purpose: The primary objective of this single arm study is to compare the sensitivity and specificity of acoustic angiography with traditional b-mode ultrasound in the distinction of malignant versus benign breast lesions. Secondary objectives include a comparison of area under the curve (AUC) for acoustic angiography versus b-mode ultrasound, and comparison of radiologist preference for the two imaging techniques for each of 3 lesion characteristics. Participants: Sixty patients who are to have a clinical surgical breast biopsy based on results from pre-study standard of care (SOC) imaging will be recruited from the UNC Breast Clinic for participation in the study. Procedures (methods): This is a one arm single center study of patients with suspicious breast lesions (BIRADS 4 or 5) from the UNC Breast Clinic that consent to undergo an acoustic angiography in conjunction with b-mode ultrasound prior to their scheduled biopsy.
Detailed description
Increasing the sensitivity and specificity of diagnostic imaging in patients at high risk for breast cancer could provide substantial clinical benefit by improving diagnosis, preventing over-treatment, and reducing healthcare costs. Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density. It evaluates tumor micro-vasculature and may provide a powerful prognostic tool for the diagnosis of breast cancer, and eventually for treatment evaluation. Sixty patients who are to have a clinical surgical breast biopsy based on results from pre-study standard of care (SOC) imaging will be recruited from the UNC Breast Clinic for participation in the study. The primary objective of this single arm study is to compare the sensitivity and specificity of acoustic angiography with traditional b-mode ultrasound in the distinction of malignant versus benign breast lesions. Secondary objectives include a comparison of area under the curve (AUC) for acoustic angiography versus b-mode ultrasound, and comparison of radiologist preference for the two imaging techniques for each of 3 lesion characteristics.
Interventions
DEVICEAcoustic Angiography
Acoustic angiography imaging involves a research high frequency ultrasound scanner and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes.
DRUGDefinity
Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed). Perflutren is a diagnostic drug that is intended to be used for contrast enhancement. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic solution which is activated by mechanical agitation with Vialmix®.It will be dispensed in inactivated form to a study team member. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.
Sponsors
National Cancer Institute (NCI)
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Experimental: Acoustic Angiography
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subject must meet all of the inclusion criteria to participate in this study: 1. Women ≥18 years old 2. Patient had a diagnostic breast ultrasound study performed at UNC 3. Scheduled for a core needle or surgical breast biopsy of at least one breast lesion that is 2 cm or less in size and 3 cm in depth from the skin surface 4. Lesion visualized on ultrasound 5. Able to provide informed consent 6. Negative urine pregnancy test in women of child-bearing potential
Exclusion criteria
All subjects meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and Specificity | 2 years | To compare (using a reader study) the sensitivity and specificity of acoustic angiography to the sensitivity and specificity of conventional b-mode ultrasound in evaluation of breast lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiologist Preference | 2 years | To compare radiologist preference of acoustic angiography to conventional b-mode ultrasound for each lesion characteristic (shape, margins and vascularity) |
| Area Under the Curve (AUC) of Acoustic Angiography | 2 years | To compare the area under the curve (AUC) of acoustic angiography to the AUC of the b-mode ultrasound To compare radiologist preference of acoustic angiography to conventional b-mode ultrasound for each lesion characteristic (shape, margins, and vascularity) Primary Endpoint Sensitivity and specificity for our study is defined as the ability of readers (radiologists) to use the acoustic angiography or b-mode ultrasound to distinguish between malignant and non-malignant breast lesions known to exist based on pathological results (the gold standard). The AUC of acoustic angiography compared to the AUC of b-mode ultrasound |
| Vessel Tortuosity (No Units) | 2 years | To quantify vessel tortuosity metrics for the acoustic angiograph images, and to use these metrics to develop a model for predicting malignancy (a model-based malignancy score) |
| Model-based Malignancy Score (Arbitrary Units) | 2 years | To compare the model-based malignancy score to the acoustic angiography reader study |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acoustic Angiography All clinical patients will be included in the experimental group.
Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. | 5 |
| Image Optimization In addition to clinical patients, 30 participants will be recruited to aid in optimizing the imaging parameters.
Acoustic Angiography: Acoustic angiography imaging involves a research high frequency ultrasound scanner and a prototype transducer as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. The imaging also requires administration of Definity ultrasound contrast agent. | 15 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not meet full criteria for inclusion after enrollment | 2 | 0 |
Baseline characteristics
| Characteristic | Acoustic Angiography | Image Optimization | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 15 Participants | 20 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 4 | 26 years STANDARD_DEVIATION 11 | 31 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 14 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 4 Participants | 8 Participants | 12 Participants |
| Region of Enrollment United States | 5 participants | 15 participants | 20 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 8 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 15 |
| other Total, other adverse events | 0 / 3 | 3 / 15 |
| serious Total, serious adverse events | 0 / 3 | 0 / 15 |
Outcome results
Primary
Sensitivity and Specificity
To compare (using a reader study) the sensitivity and specificity of acoustic angiography to the sensitivity and specificity of conventional b-mode ultrasound in evaluation of breast lesions
Time frame: 2 years
Population: The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.
Secondary
Area Under the Curve (AUC) of Acoustic Angiography
To compare the area under the curve (AUC) of acoustic angiography to the AUC of the b-mode ultrasound To compare radiologist preference of acoustic angiography to conventional b-mode ultrasound for each lesion characteristic (shape, margins, and vascularity) Primary Endpoint Sensitivity and specificity for our study is defined as the ability of readers (radiologists) to use the acoustic angiography or b-mode ultrasound to distinguish between malignant and non-malignant breast lesions known to exist based on pathological results (the gold standard). The AUC of acoustic angiography compared to the AUC of b-mode ultrasound
Time frame: 2 years
Population: The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.
Secondary
Model-based Malignancy Score (Arbitrary Units)
To compare the model-based malignancy score to the acoustic angiography reader study
Time frame: 2 years
Population: The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.
Secondary
Radiologist Preference
To compare radiologist preference of acoustic angiography to conventional b-mode ultrasound for each lesion characteristic (shape, margins and vascularity)
Time frame: 2 years
Population: The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.
Secondary
Vessel Tortuosity (No Units)
To quantify vessel tortuosity metrics for the acoustic angiograph images, and to use these metrics to develop a model for predicting malignancy (a model-based malignancy score)
Time frame: 2 years
Population: The data were unable to be analyzed because we could not visualize the vessels to calculate this value. The system was unable to achieve the imaging resolution to visualize the vasculature.