Medical Imaging and Focused Ultrasound Treatment for Breast Tumors Using Harmonic Motion Imaging (HMI)
Study Overview
Status
Conditions
Detailed Description
The objectives of this study are to demonstrate the initial clinical feasibility of using Harmonic Motion Imaging (HMI) for guiding and monitoring 1) Focused Ultrasound Surgery (FUS) in patients with benign tumors and stage 1 non-metastatic breast cancers and 2) microbubble-mediated Low Intensity Focused Ultrasound (LIFU), i.e., sonoporation, in early-stage, non-metastatic breast cancer patients. The secondary objective is to investigate the correlation between HMI-informed treatment response with patients' post-treatment immune profile.
FUS is a non-invasive, non-ionizing treatment procedure that precisely focuses and delivers a large amount of ultrasound energy to the target area, causing a localized temperature rise and cell necrosis at the target. Patients with small solid tumors without positive lymph nodes have the highest survival rate. However, especially for patients with benign tumors (most common in younger women) and older patients (>65 years old) who fit these criteria, an alternative treatment technique that is far less invasive than the current surgical or invasive ablative intervention may be more beneficial. The main advantage of treating breast tumors with focused ultrasound ablation (FUS) is its noninvasiveness, i.e., no need for surgery. Without surgery, recovery from the procedure is much faster, patients may experience less pain, and cosmetic results may be improved.
On the other hand, microbubbles have been approved for use by the FDA in contrast-enhanced ultrasound imaging, e.g., cardiac and liver imaging. Research has shown that microbubble mediated LIFU can improve intratumoral drug uptake via a phenomenon termed sonoporation, as a result of cavitation of microbubbles. Sonoporation does not cause any unexpected bias or additional toxicity compared with chemotherapy alone. Currently, sonoporation lacks imaging guidance. In this study, HMI and contrast-enhanced power Doppler will be investigated to guide and monitor sonoporation. Microbubbles will be injected at an FDA-approved dose and route.
HMI is an ultrasound elasticity method that can provide measurements of the locally generated mechanical response and inherent mechanical properties of tissues. The result is a new image that contains unique localized information on the relative stiffness in and around the tumor. HMI can be performed simultaneously with HIFU ablation so that HIFU ablation can be monitored with HMI without interruption of HIFU treatment. When used for monitoring thermal ablation using FUS, the integrated system is referred to as HMIgFUS, which stands for Harmonic Motion Imaging for Focused Ultrasound. The resulting synchronous monitoring system has the ability to follow and identify the areas of necrosis. This study aims to evaluate the HMI technique for monitoring FUS ablation in a clinical setting and investigate the correlation between HMI-monitored displacement and patients' immune response.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Shiqi Hu, MSc
- Phone Number: 917-664-5382
- Email: sh4193@columbia.edu
Study Locations
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New York
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New York, New York, United States, 10032
- Recruiting
- Columbia University Irving Medical Center/NYP
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Principal Investigator:
- Bret Taback, MD
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Contact:
- Shiqi Hu, MSc
- Phone Number: 917-664-5382
- Email: sh4193@columbia.edu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Focused Ultrasound Surgery
Inclusion criteria:
- Women age 18 years or older with benign tumors or early-stage, non-metastatic breast cancer (stage I without the involvement of axillary lymph nodes)
- Scheduled to receive surgical resection of the tumor by their clinical care team
Exclusion criteria:
- Patients who have received or are scheduled to receive thermal ablation or treatment of the tumor as part of their clinical care
- Pregnant or lactating
- Presence of breast implants
- Have a history of laser or radiation therapy to the targeted breast.
Microbubble-mediated LIFU, i.e., sonoporation
Inclusion criteria:
- Women 18 years or older
- Deemed eligible to receive neoadjuvant systemic therapy as per the treating physician, with the dose and schedule deemed appropriate by the treating physician
- Any stage invasive breast cancer provided the primary breast tumor size is at least 4 mm
Exclusion criteria:
- Pregnant or lactating
- Presence of breast implants
- History of laser or radiation therapy to the affected breast
- Contraindication history or hypersensitivity to ultrasound contrast agents, e.g., Definity, including polyethylene glycol (PEG) allergy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: HMIgFUS
Each study participants' tumors will be imaged using Harmonic Motion Imaging (HMI), an ultrasound elastography method.
A central portion of the tumor will then be ablated and monitored using Harmonic Motion Imaging guided Focus Ultrasound (HMIgFUS).
Only one portion of the tumor will be ablated; the other portions of the tumor, including tumor margins, will not be ablated.
Following ablation, the tumor will be imaged again using HMI.
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Harmonic motion imaging guided focused ultrasound (HMIgFUS) is a combined treatment and imaging method, in which focused ultrasound (FUS) is used to thermally ablate tissue and harmonic motion imaging (HMI) is used for FUS guidance and monitoring. FUS applies high intensity focused ultrasound waves at its specified target to heat the tissue over a specified duration, causing cell death at the target area. HMI is an elasticity imaging technique which induces dynamic tissue vibrations at the target for tissue elasticity characterization. One of the inclusion criteria for this study is that participants must be scheduled for surgical excision of their breast tumor. In this study, HMIgFUS will be applied to anesthetized participants immediately prior to their scheduled surgery. HMI imaging will also be performed immediately prior to and after HMIgFUS application. |
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Experimental: HMIgLIFU
Eligible participants have early-stage breast cancers and are scheduled to receive neoadjuvant chemotherapy as part of their clinical care.
On the day of chemotherapy infusion, elasticity images of the lesions and surrounding tissues will be collected using HMI before infusion after tumor identification on ultrasound imaging.
Within an hour after infusion, the participants' tumors will be treated with microbubble-mediated Low-Intensity Focused Ultrasound (LIFU), i.e. sonoporation.
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Microbubble-mediated Low Intensity Focused Ultrasound (LIFU) is a minimally invasive procedure which delivers localized ultrasound energy to the target region, causing cavitation of microbubbles to safely and transiently increase the permeability of vessels that aids local delivery of medicine.
Other Names:
Definity is a diagnostic ultrasound enhancing agent used to improve the clarity of echocardiograms and other ultrasound images.
It consists of tiny, gas-filled lipid microspheres (about the size of a red blood cell) that circulate in the bloodstream to reflect ultrasound waves.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Number of patients with ablation
Time Frame: From the date of ablation and imaging to the date of pathological results (approximately 1 week)
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To identify markers of ablation progression using HMIgFUS images, thereby predicting whether ablation occurred or not.
The investigators will also use differences in HMI imaging performed before and after ablation to assess the presence of ablation.
The results from both of these methods will be validated with pathological findings, to determine whether ablation was achieved.
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From the date of ablation and imaging to the date of pathological results (approximately 1 week)
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R2 value of ablated lesion depth
Time Frame: From the date of ablation and imaging to the date of pathological results (approximately 1 week)
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The depth of the lesion (in mm away from the surface of the skin) as shown on HMIgFUS images will be compared and validated with pathological findings.
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From the date of ablation and imaging to the date of pathological results (approximately 1 week)
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R2 value of ablated lesion width
Time Frame: From the date of ablation and imaging to the date of pathological results (approximately 1 week)
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The width of the lesion (in mm laterally across the lesion) as shown on HMIgFUS images will be compared and validated with pathological findings.
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From the date of ablation and imaging to the date of pathological results (approximately 1 week)
|
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R2 value of ablated lesion area
Time Frame: From the date of ablation and imaging to the date of pathological results (approximately 1 week)
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The area of the lesion (in mm^2) as shown on HMIgFUS images will be compared and validated with pathological findings.
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From the date of ablation and imaging to the date of pathological results (approximately 1 week)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Bret Taback, MD, Columbia University
Publications and helpful links
General Publications
- Han Y, Wang S, Payen T, Konofagou E. Fast lesion mapping during HIFU treatment using harmonic motion imaging guided focused ultrasound (HMIgFUS) in vitro and in vivo. Phys Med Biol. 2017 Apr 21;62(8):3111-3123. doi: 10.1088/1361-6560/aa6024. Epub 2017 Mar 21.
- Han Y, Wang S, Hibshoosh H, Taback B, Konofagou E. Tumor characterization and treatment monitoring of postsurgical human breast specimens using harmonic motion imaging (HMI). Breast Cancer Res. 2016 May 9;18(1):46. doi: 10.1186/s13058-016-0707-3.
- Hernot S, Klibanov AL. Microbubbles in ultrasound-triggered drug and gene delivery. Adv Drug Deliv Rev. 2008 Jun 30;60(10):1153-66. doi: 10.1016/j.addr.2008.03.005. Epub 2008 Apr 3.
- Pitt WG, Husseini GA, Staples BJ. Ultrasonic drug delivery--a general review. Expert Opin Drug Deliv. 2004 Nov;1(1):37-56. doi: 10.1517/17425247.1.1.37.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms
- Neoplasms by Histologic Type
- Neoplasms, Glandular and Epithelial
- Skin Diseases
- Breast Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms, Connective Tissue
- Neoplasms, Fibrous Tissue
- Neoplasms, Fibroepithelial
- Skin and Connective Tissue Diseases
- Breast Neoplasms
- Fibroadenoma
- Equipment and Supplies
- perflutren
- Microbubbles
Other Study ID Numbers
- AAAS9859
- 5R01CA228275 (U.S. NIH Grant/Contract)
- 1R01CA301199-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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