Contrast-Enhanced Ultrasound and Shear Wave Elastography for the Treatment of Lymphedema

Study Overview
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Brief Summary
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The purpose of this research is to determine the preferred microbubble agent (Lumason®, Optison®, and Definity®) for lymphatic channel visualization by ultrasound. This research will also evaluate the utility of preoperative high-frequency B-mode ultrasound with contrast-enhanced ultrasound for presurgical planning, and ultrasound shear wave elastography for assessing treatment response at 6-month follow up.

Detailed Description
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Part 1 - Evaluate the uptake of microbubble agent (Lumason®, Optison®, and Definity®) for lymphatic visualization by ultrasound. Part 2 - Combine preoperative high-frequency B-mode ultrasound with contrast-enhanced ultrasound to identify patent lymphatic channels for lymphaticovenous anastomosis presurgical planning. Evaluate the utility of ultrasound shear wave elastography for assessing treatment response at 6-month follow up.

Official Title
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Contrast-enhanced Ultrasound and Shear Wave Elastography for the Treatment of Lymphedema (CASTLE) Study

Conditions
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Lymphedema Arm

Intervention / Treatment
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* Drug: Lumason
* Drug: Optison
* Drug: Definity


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unilateral lymphedema in the upper extremity (ISL stage 2 or 3) secondary to breast cancer or breast cancer treatment. Patient qualifies for LVA surgery as determined by the plastic surgeons performing the surgery (Dr. Bill Tran or Dr. Vahe Fahradyan), and the patient consents to surgery. Patient must be able to come to the 6-month clinical follow-up appointment (Part 2 only). Patients must be able to understand the study procedures and comply with them for the entire length of the study. No contraception is necessary or required. Exclusion Criteria: Pregnant or nursing women. Known or suspected hypersensitivity to microbubble contrast agent, perflutren, blood products, albumin, polyethylene glycol (PEG), or egg.31. Known or suspected cardiac shunts. Prior lymphedema surgery in the upper extremity. Tattoo or scar on either upper extremity. Current drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements. Inability or unwillingness of individual or legal guardian/representative to give written informed consent.. Current or past participation within a specified timeframe in another clinical trial, as warranted by the administration of this intervention.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Microbubble contrast agent Lumason<br>While subjects are undergoing standard of operation for arm with lymphedema, the healthy arm will receive intradermal injection of microbubbles and imaged immediately by ultrasound. | Drug: Lumason<br>* Ultrasound microbubble contrast agent intradermal 0.2-0.3 cc of microbubble suspension per injection, 10-12 total injections per upper extremity<br>* Other names: sulfur hexafluoride lipid-type A microspheres;|
| Other: Microbubble contrast agent Optison<br>While subjects are undergoing standard of operation for arm with lymphedema, the healthy arm will receive intradermal injection of microbubbles and imaged immediately by ultrasound. | Drug: Optison<br>* Ultrasound microbubble contrast agent intradermal 0.2-0.3 cc of microbubble suspension per injection, 10-12 total injections per upper extremity<br>* Other names: perflutren protein-type A microspheres;|
| Other: Microbubble contrast agent Definity<br>While subjects are undergoing standard of operation for arm with lymphedema, the healthy arm will receive intradermal injection of microbubbles and imaged immediately by ultrasound. | Drug: Definity<br>* Ultrasound microbubble contrast agent intradermal 0.2-0.3 cc of microbubble suspension per injection, 10-12 total injections per upper extremity<br>* Other names: perflutren lipid microsphere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lymphatic vessel visualization | The time from injection to lymphatic visualization, the duration of contrast visualization, and the longest length of lymphatic channel visualized for each injection site will be determined | 5 minutes after injection | 
| High-frequency ultrasound and shear-wave elastography | Identify any patent lymphatic channels on CEUS or high-frequency ultrasound that were not detected by the reference standard ICG lymphography. We will additionally measure dermal thickness on B-mode ultrasound and perform SWE at levels comparable to the lymphedema grading metrics routinely collected at surgical visits. | 1.5 hours for intraoperative CEUS and out-patient SWE both at baseline and 6-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphaticovenous anastomosis surgery