Academic-Industrial Partnership for Translation of Acoustic Angiography
Condition: Signs and Symptoms
Intervention: Acoustic Angiography; Definity
Intervention description: 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.; 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.
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Experimental: Acoustic Angiography
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ultrasound; breast; angiography

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.
    

Eligibility criteria:

        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.