Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Diseases and Abnormalities at or Before Birth

Breast Neoplasms

Congenital Abnormalities

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)

3D HI and SHI of UCA

Flemming Forsberg, phD

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.

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.

Quantitative Subharmonic Breast Imaging

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.

Quantitative measures of the vascular volumes of breast lesions determined by SHI utilizing bifurcations and vessel length, and blood pool and parametric imaging

National Cancer Institute (NCI)

Lantheus Medical Imaging

University of California, San Diego

Thomas Jefferson University

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)

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)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Flemming Forsberg

Power Doppler Imaging (PDI) : Benign

Power Doppler Imaging (PDI) : Malignant

Power Doppler Imaging (PDI) : Not Characterized

3D SHI : Benign

3D SHI : Malignant

3D SHI : Not Characterized

Harmonic Imaging (HI) : Benign

Harmonic Imaging (HI) : Malignant

Harmonic Imaging (HI) : Not Characterized

Number of Breast Cancer Lesions Characterized as Malignant or Benign With 3D SHI, Harmonic Imaging (HI) or Power Doppler Imaging (PDI)

Central Benign lesions

Peripheral benign lesions

Central malignant lesions

peripheral malignant lesions

Change in Vascular Volume of Breast Lesions as Assessed by Subharmonic Imaging (SHI) Signal Intensity

Overall Study

Breast Diseases

Skin Diseases

Subdermal low (1.0 ml) or high (2.0 ml) dose injection of the ultrasound contrast agent Sonazoid divided into four individual aliquots at four locations (12, 3, 6, and 9 o'clock) around a 2 cm in diameter region in the mid-upper outer quadrant of the left breast, followed a week later by the other dose injected in the same fashion into the right breast.

Subdermal injection of the ultrasound contrast agent of Sonazoid divided into four individual aliquots at four locations (12, 3, 6, and 9 o'clock) around the breast cancer. Subjects will receive an injection of either a low (1.0 ml) or a high (2.0 ml) dose of Sonazoid depending on the outcome of the Part 1 safety and tolerability study.

subdermal injection into the breast of Sonazoid (1 or 2 ml) divided into four individual aliquots at four locations (12, 3, 6, and 9 o'clock)

Sonazoid; Perflubutane for Injection

Flemming Forsberg, PhD

This is a two part, open label, non-randomized trial of women with a breast cancer diagnosis scheduled for excisional surgery and sentinel lymph node (SLN) evaluation.

Part 1 is a two-period, crossover, dose-finding study, which will be performed in 12 healthy female volunteers to determine the optimal dose as well as the safety and tolerability of the tissue-specific, contrast agent Sonazoid (GE Healthcare, Oslo, Norway) for human lymphatic applications. In Part 2 lymphosonographic SLN identification will be compared to that of isotope mapping during surgery on 90 female, breast cancer patients.

This is a two part, open-label, non-randomized trial that will be conducted at Thomas Jefferson University (TJU). Initially in Part 1, a two-period, crossover, dose-finding study will be performed in 12 healthy female volunteers to determine the optimal dose as well as the safety and tolerability of the tissue-specific, contrast agent Sonazoid (GE Healthcare, Oslo, Norway) for human lymphatic applications. Each volunteer will receive an injection of a low or a high dose in a blinded, sequence-randomized allocation schedule. Screening and baseline assessments/procedures will be obtained. Each volunteer will receive their subdermal, low or high dose of Sonazoid divided into four individual aliquots at four locations (12, 3, 6, and 9 o'clock) around a 2 cm in diameter region in the mid-upper outer quadrant of the left breast.

Contrast enhanced ultrasound imaging (CEUS) will be performed immediately after Sonazoid administration (i.e., lymphosonography) to identify the number, location and course of the lymphatic channels (LCs) and SLNs using a S3000 scanner (Siemens Medical Solutions, Mountain View, CA) with a high frequency, broad bandwidth linear array. CEUS evaluations will be repeated at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours and 24 hours post Sonazoid administration. The safety and tolerability of Sonazoid will be closely monitored throughout this safety and tolerability, dose-finding study.

Following at least a one week of washout, the upper outer quadrant of the right breast will be injected with the alternate dose of Sonazoid and lymphosonography will again be used to identify the number, location and course of the LCs and SLNs. Volunteers who received the low dose during their first visit will receive the high dose the next time around and vice versa in a 1:1 ratio. All procedures from the initial visit will be repeated (see above), except that the left breast (injected initially) will be assessed sonographically for the presence of contrast-enhanced tissues (injection site as well as lymphatic structures) prior to contrast administration in the right breast.

In Part 2 lymphosonography will compare SLN identification to that of isotope mapping during surgery on 90 female, breast cancer patients. A state-of-the-art S3000 scanner with contrast-specific imaging capabilities will be used to localize lymphatic drainage from breast cancers after subdermal administration of Sonazoid. The number and locations of the SLNs identified by the two imaging modalities (CEUS and isotope mapping) will be compared with dye-guided surgery as the reference standard for SLN detection. Moreover, as each SLN is resected it will be assessed ex vivo for the presence of radioactivity (using a gamma probe), Sonazoid (using CEUS) and blue dye (via visual inspection by the surgeon). All SLNs that are surgically removed will be documented and sent for histopathologic evaluation.

Trial Population: Part 1 will consist of 12 healthy, adult female volunteers in the initial safety, tolerability and dosing study.

In Part 2, 90 adult women, who have breast cancer and are scheduled for a surgical excision and SLN evaluation, will be enrolled in a clinical trial at TJU.

Statistical Methodology: Our statistical analysis will address four major questions:

* Is subdermal administration of Sonazoid in humans safe and tolerable?
* Can an optimal and efficacious dose of Sonazoid for lymphosonography be established?
* Does lymphosonography identify more SLNs in patients with breast cancer than isotope mapping (with Tc-99m sulfur colloids)?
* Does lymphosonography identify more SLNs with metastatic deposits in patients with breast cancer compared to isotope mapping?

Contrast Ultrasound Detection of Sentinel Lymph Nodes

Contrast Ultrasound Detection of Sentinel Lymph Nodes in Breast Cancer Patients

De-identified data will be made available to the research community upon request after the completion of the study in accordance with NIH rules and regulations.

To establish, in healthy, female volunteers, the optimal dose of subdermaly administrated Sonazoid (an ultrasound contrast agent) employed for contrast enhanced ultrasound imaging (CEUS)

To assess the safety and tolerability of subdermal administration of Sonazoid in 12 female, healthy volunteers.

To determine if CEUS of subdermally administrated Sonazoid (i.e., lymphosonography) identify more sentinel lymph nodes (SLNs) in patients with breast cancer compared to isotope mapping (with Tc-99m sulfur colloids) using blue dye and surgical dissection as the reference standard. The fundamental hypothesis is that on average lymphosonography will detect 3.2 SLNs compared to 2.7 with isotope mapping.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Quantitative Subharmonic Breast Imaging	NCT01490892	Breast Cancer	3D HI and SHI o...	18 Years -	Thomas Jefferson University
Quantitative Subharmonic Breast Imaging	NCT01490892	Breast Cancer	3D HI and SHI o...	18 Years -	Thomas Jefferson University
Contrast Ultrasound Detection of Sentinel Lymph Nodes	NCT02652923	Breast Cancer	Sonazoid; Perfl...	21 Years -	Thomas Jefferson University

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