3-D Super Resolution Ultrasound Microvascular Imaging

High Frame Rate 3-D Super Resolution Ultrasound Microvascular Imaging

This is a 3-arm single center study of 45 patients. These cohorts will include 15 breast patients scheduled to undergo a biopsy, and 15 thyroid patients scheduled to undergo fine needle aspiration, biopsy, or thyroidectomy that consent to undergo an acoustic angiography in conjunction with b-mode ultrasound prior to their scheduled biopsy. Prior to imaging clinical patients, the third arm will include 15 healthy volunteers that will be imaged to optimize imaging parameters.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Thyroid Cancer
• Intervention / Treatment: Drug: Definity; Device: Acoustic Angiography

Detailed Description

Increasing the sensitivity and specificity of diagnostic imaging in patients at high risk for breast or thyroid cancer could provide substantial clinical benefit by improving diagnosis, preventing over-treatment, and reducing healthcare costs. Acoustic angiography is a new type of contrast enhanced ultrasound imaging which is specifically sensitive to microvascular structure and density. It evaluates tumor micro-vasculature and may provide a powerful prognostic tool for the diagnosis of breast cancer, and eventually for treatment evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carly Sronce; Phone Number: 9199663262; Email: carly_sronce@med.unc.edu
• Study Contact Backup: Name: Desma Jones, CCRC; Phone Number: 9198439463; Email: desma_jones@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • Univeristy of North Carolina Chapel Hill
      • Contact: Desma Jones, CCRC; Phone Number: 9198439463; Email: desma_jones@med.unc.edu
      • Contact: Carly Sronce; Phone Number: 919-966-3262; Email: carly_sronce@med.unc.edu
      • Principal Investigator: Yueh Lee, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Healthy Volunteers

Inclusion Criteria

• Able to provide informed consent
• Negative urine pregnancy test in women of child-bearing potential

Exclusion Criteria

• Institutionalized subject (prisoner or nursing home patient)
• Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)
• Known hypersensitivity to perflutren lipid (Definity®)

• Active cardiac disease including any of the following:

  • Severe congestive heart failure
  • Unstable angina.
  • Severe arrhythmia
  • Myocardial infarction within 14 days prior to the date of proposed Definity® administration.
  • Pulmonary hypertension
  • Cardiac shunts

Breast Imaging Patients

Inclusion Criteria

• Women
• Patient had a diagnostic breast ultrasound study performed at UNC
• Scheduled for a core needle or surgical breast biopsy of at least one breast lesion that is 2 cm or less in size and 3 cm in depth from the skin surface
• Able to provide informed consent
• Negative urine pregnancy test in women of child-bearing potential
• BIRADS score of 4 or 5.

Exclusion Criteria

• Male
• Institutionalized subject (prisoner or nursing home patient)
• Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)
• Sonographically visible breast lesion larger than 2cm or greater than 3cm in depth from the skin surface
• Known hypersensitivity to perflutren lipid (Definity®)

• Active cardiac disease including any of the following:

  • Severe congestive heart failure
  • Unstable angina.
  • Severe arrhythmia
  • Myocardial infarction within 14 days prior to the date of proposed Definity® administration.
  • Pulmonary hypertension
  • Cardiac shunts

Thyroid Imaging Patients Inclusion Criteria

• Patient had a diagnostic thyroid ultrasound study performed at UNC
• TIRADS risk score of 4c or 5
• Scheduled for a core needle or surgical thyroid biopsy, fine needle aspiration, or thyroidectomy of at least one sonographically visible thyroid lesion that is 3 cm in depth from the skin surface
• Able to provide informed consent
• Negative urine pregnancy test in women of child-bearing potential

Exclusion Criteria

• Institutionalized subject (prisoner or nursing home patient)
• Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)
• Known hypersensitivity to perflutren lipid (Definity®)

• Active cardiac disease including any of the following:

  • Severe congestive heart failure
  • Unstable angina.
  • Severe arrhythmia
  • Myocardial infarction within 14 days prior to the date of proposed Definity® administration.
  • Pulmonary hypertension
  • Cardiac shunts

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Breast Imaging Cohort; A total of 15 women with known breast lesions that are already scheduled to undergo a clinical biopsy	Drug: Definity; Perflutren will be administered in split doses using the dosing range and administration type IV bolus) within the perflutren prescribing information. When administered as a bolus, the package insert recommends 10 uL/kg patient weight administered within 30-60 seconds, followed by a 10mL saline flush with a second dose of 10 uL/kg patient weight 30 minutes following the first dose, if needed.; Other Names: perflutren; Device: Acoustic Angiography; Acoustic angiography imaging involves a research ultrasound scanner as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. Imaging will be performed within the package insert guidelines for ultrasound system mechanical index (a measurement of output power) when imaging perflutren contrast agent (less than 0.8). Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes.
Experimental: Thyroid Imaging Cohort; A total of 15 participants with known thyroid lesions that are already scheduled to undergo a clinical biopsy	Drug: Definity; Perflutren will be administered in split doses using the dosing range and administration type IV bolus) within the perflutren prescribing information. When administered as a bolus, the package insert recommends 10 uL/kg patient weight administered within 30-60 seconds, followed by a 10mL saline flush with a second dose of 10 uL/kg patient weight 30 minutes following the first dose, if needed.; Other Names: perflutren; Device: Acoustic Angiography; Acoustic angiography imaging involves a research ultrasound scanner as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. Imaging will be performed within the package insert guidelines for ultrasound system mechanical index (a measurement of output power) when imaging perflutren contrast agent (less than 0.8). Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes.
Experimental: Healthy Volunteers Cohort; A total of 15 participants will be included to optimize imaging parameters.	Drug: Definity; Perflutren will be administered in split doses using the dosing range and administration type IV bolus) within the perflutren prescribing information. When administered as a bolus, the package insert recommends 10 uL/kg patient weight administered within 30-60 seconds, followed by a 10mL saline flush with a second dose of 10 uL/kg patient weight 30 minutes following the first dose, if needed.; Other Names: perflutren; Device: Acoustic Angiography; Acoustic angiography imaging involves a research ultrasound scanner as well as conventional b-mode ultrasound to guide the location of the imaging. The conventional ultrasound will be conducted just prior to the acoustic angiography for localization. Imaging will be performed within the package insert guidelines for ultrasound system mechanical index (a measurement of output power) when imaging perflutren contrast agent (less than 0.8). Acoustic angiography imaging will be performed by trained medical personnel using mild compression to eliminate motion. Total imaging time is estimated to be less than 15 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of Acoustic Angiography; Breast Imaging (percent of positive scans)	Sensitivity of Acoustic Angiography in the analysis of know breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions.	Calculated once all imaging is complete [Anticipated 1.5 years]
Specificity of Acoustic Angiography; Breast Imaging (percent of negative scans)	Specificity of Acoustic Angiography in the analysis of know breast lesions will be evaluated by comparing image analyses to the pathological results for these lesions.	Calculated once all imaging is complete [Anticipated 1.5 years]
Sensitivity of Acoustic Angiography; Thyroid Imaging (percent of positive scans)	Sensitivity of Acoustic Angiography in the analysis of know thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions.	Calculated once all imaging is complete [Anticipated 1.5 years]
Specificity of Acoustic Angiography; Thyroid Imaging (percent of negative scans)	Specificity of Acoustic Angiography in the analysis of know thyroid lesions will be evaluated by comparing image analyses to the pathological results for these lesions.	Calculated once all imaging is complete [Anticipated 1.5 years]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve of Acoustic Angiography (arbitrary units)	To compare the area under the curve (AUC) of acoustic angiography to the AUC of the b-mode ultrasound	Calculated once all imaging is complete [Anticipated 1.5 years]
Radiologist preference (Arbitrary units)	To compare radiologist preference of acoustic angiography to conventional b-mode ultrasound for each lesion characteristic (shape, margins, and vascularity)	Calculated once all imaging is complete [Anticipated 1.5 years]
Sensitivity of acoustic angiography compared to conventional ultrasound: Breast (arbitrary units)	To compare (using a reader study) the sensitivity of acoustic angiography to the sensitivity of conventional b-mode ultrasound in evaluation of known breast lesions for predicting malignancy.	Calculated once all imaging is complete [Anticipated 1.5 years]
Specificity of acoustic angiography compared to conventional ultrasound: Breast (arbitrary units)	To compare (using a reader study) the specificity of acoustic angiography to the specificity of conventional b-mode ultrasound in evaluation of known breast lesions for predicting malignancy.	Calculated once all imaging is complete [Anticipated 1.5 years]
Sensitivity of acoustic angiography compared to conventional ultrasound: Thyroid (arbitrary units)	To compare (using a reader study) the sensitivity of acoustic angiography to the sensitivity of conventional b-mode ultrasound in evaluation of known thyroid lesions for predicting malignancy.	Calculated once all imaging is complete [Anticipated 1.5 years]
Specificity of acoustic angiography compared to conventional ultrasound: Thyroid (arbitrary units)	To compare (using a reader study) the specificity of acoustic angiography to the specificity of conventional b-mode ultrasound in evaluation of known thyroid lesions for predicting malignancy.	Calculated once all imaging is complete [Anticipated 1.5 years]

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Yueh Lee, MD, PhD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Cancer Screening
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Thyroid Diseases; Head and Neck Neoplasms; Thyroid Neoplasms
• Other Study ID Numbers: LCCC1915; R01CA220681 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results
• IPD Sharing Time Frame: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication.
• IPD Sharing Access Criteria: An investigator who proposes to use the data must have approval from an IRB, IEC, or REB, as applicable, and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No