Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

Study Overview
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Brief Summary
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This is a diagnostic accuracy study to evaluate if two novel ultrasound (US) techniques, quantitative 3D subharmonic imaging (SHI) and Subharmonic Aided Pressure Estimation (SHAPE), used with an intravenous ultrasound contrast agent (Definity, Lantheus Medical Imaging, Billerica, MA), can track changes in locally advanced breast cancer (LABC) angiogenesis and interstitial fluid pressure (IFP), respectively, by studying women undergoing neoadjuvant chemotherapy before as well as with around 10% and 60% (in part 1) or 30% (in part 2) of the neoadjuvant chemotherapy treatment delivered and after completion of the neoadjuvant chemotherapy treatment. Results will be compared to MRI and pathology.

Official Title
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Quantitative Subharmonic Breast Imaging: Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Definity infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females Be diagnosed with T1 or greater LABC, any N and M0. Be scheduled for neoadjuvant chemotherapy Be at least 21 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 with other primary cancers requiring systemic treatment. Patients with any metastatic disease. Patients undergoing neoadjuvant endocrine therapy. Patients with known hypersensitivity or allergy to any component of Definity. Patients with cardiac shunts or congenital heart defects. Patients with unstable cardiopulmonary conditions or respiratory distress syndrome. Patients with uncontrollable emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli. Patients who have received any contrast medium (X-ray, MRI, CT or US) in the 24 hours prior to the research US exam.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Definity infusion<br>Infusion of Definity (Perflutren Lipid Microspheres) | Drug: Definity infusion<br>* 3 ml of Perflutren Lipid Microspheres (Definity) mixed in 50 ml of saline is infused at a rate of approximately 4ml/min<br>* Other names: Perflutren Lipid Microspheres;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Complete Responders | To evaluate the ability of SHAPE, used with Definity, to track changes in interstitial fluid pressure (IFP) by studying women undergoing neoadjuvant chemotherapy before as well as with around 10% and 30% of the neoadjuvant chemotherapy treatment delivered and comparing results to MRI and pathology. | from baseline to completion of neoadjuvant chemotherapy, average of 6 months | 
| Subharmonic Aided Pressure Estimation (SHAPE) After Treatment for Partial Responders | To evaluate the ability of SHAPE, used with Definity, to track changes in interstititial fluid (IFP) by studying women undergoing neoadjuvant chemotherapy before as well as with around 10% 30% of the neoadjuvant chemotherapy treatment delivered and after completion of the neoadjuvant chemotherapy treatment and comparing results to MRI and pathology. | from baseline to completion of neoadjuvant chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subharmonic Imaging (SHI) Depiction of Breast Cancer Angiogenesis for Complete Responders | To compare the 3D Subharmonic imaging (SHI) depiction of breast cancer angiogenesis in humans to CD31, an immunohistochemical predictor of angiogenesis. | From baseline to after surgery | 
| SHI Depiction of Breast Cancer Angiogenesis for Partial Responders | To compare the 3D SHI depiction of breast cancer angiogenesis in humans to CD31, an immunohistochemical predictor of angiogenesis. | After surgery; on average 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Interstitial fluid pressure, Angiogenesis, Contrast enhanced ultrasound imaging, Subharmonic imaging, Subharmonic pressure estimation