Academic-Industrial Partnership for Translation of Acoustic Angiography

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.

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 exclusion criteria at baseline will be
excluded from study participation

1. 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)

2. Institutionalized subject (prisoner or nursing home patient)

3. Critically ill or medically unstable and whose critical course during the observation
period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)

4. Sonographically visible breast lesion larger than 2cm or greater than 3cm in depth
from the skin surface

5. Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid
(Definity®)

6. 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).

7. 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.