Quantitative Subharmonic Breast Imaging

This is a non-randomized trial of 450 women with a breast abnormality, who are scheduled for a breast biopsy of this abnormality. The study will be conducted at two clinical sites. The primary objective of this trial is:

To evaluate if quantitative 3D Subharmonic imaging (SHI) or pulse inversion harmonic imaging (HI) can improve the characterization of benign and malignant breast masses (independently or in combination with other imaging modes) compared to x-ray mammography, fundamental grayscale ultrasound (US) or power Doppler imaging (PDI).

The secondary aim of this trial is:

To compare quantitative (bifurcations & vessel length) and semi-quantitative (blood pool & parametric imaging) measures of the vascular morphology of breast lesions determined by pathology and by SHI.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: 3D HI and SHI of UCA

Detailed Description

This is an open-label, non-randomized trial that will be conducted at two clinical sites (the Breast Imaging Centers at Thomas Jefferson University (TJU) Hospital and University of California, San Diego (UCSD) Hospital). All 450 subjects will receive at most two IV bolus injections of Definity (Lantheus Medical Imaging, Billerica, MA), will undergo an unenhanced (baseline) and Definity contrast-enhanced US imaging study for evaluation of a breast mass or breast abnormality without mass, and will be scheduled to undergo a clinically indicated biopsy of the breast lesion under investigation.

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Dept of Radiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Be a female diagnosed by x-ray mammography (performed within 90 days prior to the study procedure) as having a solid breast mass or abnormal area without a mass.
• Be scheduled for a biopsy (core / excisional / lumpectomy) of the mass or region of abnormality or for mastectomy within 30 days after this study procedure.
• Be at least 18 years of age.
• Be medically stable.
• If a female of child-bearing potential, must have a negative pregnancy test.
• Have signed Informed Consent to participate in the study.

Exclusion Criteria:

• Males
• Females who are pregnant or nursing.
• Patients whose breast lesion is unequivocally a cyst by unenhanced US.
• Patients currently on chemotherapy or with other primary cancers requiring systemic treatment.
• Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable. For example:
• Patients on life support or in a critical care unit.
• Patients with unstable occlusive disease (eg, crescendo angina)
• Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia.
• Patients with uncontrolled congestive heart failure (NYHA Class IV)
• Patients with recent cerebral hemorrhage.
• Patients with clinically significant and unstable renal and/or liver disease (eg, transplant recipients in rejection)
• Patients who have undergone surgery within 24 hours prior to the study sonographic examination.
• Patients with known hypersensitivity to perflutren
• Patients who have received any contrast medium (X-ray, MRI, CT, of US) in the 24 hours prior to the research US exam
• Patients with cardiac shunts.
• Patients with congenital heart defects.
• Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli.
• Patients with confirmed or suspected liver lesions.
• Patients with respiratory distress syndrome.
• Patients who have had excisional biopsy/lumpectomy of the current area of interest within the past 6 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 3D HI and SHI of UCA; Perflutren injection, suspension (IV)0.25 ml followed by 3D Harmonic imaging (HI) then (IV) 20 micro-l/kg followed by 3D subharmonic imaging (SHI)	Drug: 3D HI and SHI of UCA; Perflutren injection, suspension (IV)0.25 ml followed by 3D Harmonic imaging (HI) then (IV) 20 micro-l/kg followed by 3D subharmonic imaging (SHI); Other Names: Definity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Breast Cancer Lesions Characterized as Malignant or Benign With 3D SHI, Harmonic Imaging (HI) or Power Doppler Imaging (PDI)	Characterization of benign and malignant breast cancer lesions is compared by each imaging method which evaluates vascular activity. Imaging methods to be compared are 3D Subharmonic imaging (SHI) or pulse inversion harmonic imaging (HI), fundamental grayscale ultrasound (US) or power Doppler imaging (PDI). Data will be analyzed qualitatively.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Vascular Volume of Breast Lesions as Assessed by Subharmonic Imaging (SHI) Signal Intensity	Quantitative measures of the vascular volumes of breast lesions determined by SHI utilizing bifurcations and vessel length, and blood pool and parametric imaging	2 hours

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: National Cancer Institute (NCI); University of California, San Diego; Lantheus Medical Imaging

Publications and helpful links

General Publications

• Forsberg F, Piccoli CW, Merton DA, Palazzo JJ, Hall AL. Breast lesions: imaging with contrast-enhanced subharmonic US--initial experience. Radiology. 2007 Sep;244(3):718-26. doi: 10.1148/radiol.2443061588. Epub 2007 Aug 9.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): April 5, 2019
• Study Completion (ACTUAL): April 5, 2019

Study Registration Dates

• First Submitted: December 8, 2011
• First Submitted That Met QC Criteria: December 9, 2011
• First Posted (ESTIMATE): December 13, 2011

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: ultrasound imaging; ultrasound contrast agent; breast abnormality; subharmonic imaging
• Other Study ID Numbers: 11F.438; R01CA140338 (NIH)