Academic-Industrial Partnership for Translation of Acoustic Angiography

Study Overview
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Brief Summary
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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
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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.

Official Title
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Academic-Industrial Partnership for Translation of Acoustic Angiography

Conditions
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Signs and Symptoms

Intervention / Treatment
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* Device: Acoustic Angiography
* Drug: Definity


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject must meet all of the inclusion criteria to participate in this study: Women ≥18 years old Patient had a diagnostic breast ultrasound study performed at UNC 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 Lesion visualized on ultrasound Able to provide informed consent Negative urine pregnancy test in women of child-bearing potential Exclusion Criteria All subjects meeting any of the exclusion criteria at baseline will be excluded from study participation Male (it is uncommon for men to present for imaging and the overwhelming majority of findings are non-cancerous and do not lead to biopsy; male breast cancer represents <1% of newly diagnosed breast cancer) Institutionalized subject (prisoner or nursing home patient) Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD) Sonographically visible breast lesion larger than 2cm or greater than 3cm in depth from the skin surface Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid (Definity®) Active cardiac disease including any of the following: Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association) Unstable angina. Severe arrhythmia (i.e. ventricular tachycardia, flutter fibrillation; ventricular premature complexes occurring close to the preceding T-wave, multifocal complexes). Myocardial infarction within 14 days prior to the date of proposed Definity® administration. Uncontrolled systemic hypertension (systolic blood pressure (BP) >150 mm Hg and/or diastolic BP >90 mm Hg despite optimal medical management). Any woman who is pregnant or has reason to believe she is pregnant or any woman who is lactating (the possibility of pregnancy has to be excluded by negative urine β-HCG results, obtained within 24 hours before the perflutren lipid administration, or on the basis of patient history as defined by the UNC IRB SOP 4801 for child bearing potential) Healthy Volunteers for Image Optimization In addition to these clinical patients, 15 participants will be recruited to aid in optimizing the imaging parameters. These subjects must be willing to participate and able to provide written informed consent. However, these participants do not need to present any of the clinical indications as given for patients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Experimental: Acoustic Angiography
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acoustic Angiography<br>All clinical patients will be included in the experimental group. | Device: Acoustic Angiography<br>* 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.<br>Drug: Definity<br>* 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.<br>|
| Experimental: Image Optimization<br>In addition to clinical patients, 30 participants will be recruited to aid in optimizing the imaging parameters. | Device: Acoustic Angiography<br>* 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.<br>Drug: Definity<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2 years | 
| Radiologist Preference | To compare radiologist preference of acoustic angiography to conventional b-mode ultrasound for each lesion characteristic (shape, margins and vascularity) | 2 years | 
| 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) | 2 years | 
| Model-based Malignancy Score (Arbitrary Units) | To compare the model-based malignancy score to the acoustic angiography reader study | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ultrasound, breast, angiography