Contrast-Enhanced Subharmonic Ultrasound Imaging in Improving Characterization of Adnexal Masses in Patients Undergoing Surgery

Subharmonic Contrast Ultrasound for Improved Characterization for Adnexal Masses-A Pilot Study

This pilot clinical trial studies how well contrast-enhanced subharmonic ultrasound imaging works in improving the characterization of adnexal masses in patients undergoing surgery. Contrast-enhanced subharmonic ultrasound imaging uses high-frequency sound waves to produce images of internal organs and when combined with an ultrasound agent such as perflutren lipid microspheres, may help improve imaging and management of adnexal masses.

Study Overview

• Status: Completed
• Conditions: Adnexal Mass
• Intervention / Treatment: Drug: Perflutren Lipid Microspheres; Procedure: Contrast-Enhanced Subharmonic Ultrasound Imaging

Detailed Description

PRIMARY OBJECTIVES:

I. To develop qualitative subharmonic imaging (SHI) or SHI-derived quantitative biomarkers.

II. To generate pilot data for a study to evaluate if they improve the characterization of benign and malignant adnexal masses compared to standard ultrasound or contrast enhanced magnetic resonance imaging (MRI) or the risk of malignancy index (RMI).

SECONDARY OBJECTIVES:

I. To compare the SHI depiction of adnexal masses' neovascularity in humans to intra-tumoral microvascular density (iMVD) obtained from CD31 an immunohistochemical marker of angiogenesis.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be diagnosed with an adnexal mass
• Be scheduled for surgery to remove the adnexal mass
• Be clinically stable
• If a female of child-bearing potential, must have a negative pregnancy test
• Be conscious and able to comply with study procedures
• Have read and signed the Institutional Review Board (IRB)-approved informed consent form for participating in the study

Exclusion Criteria:

• Females who are pregnant or nursing
• Patients who have received an investigational drug in the 30 days before study drug administration, or will receive one within 72 hours (h) afterwards
• Patients with known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts
• Patients with pulmonary hypertension or unstable cardiopulmonary conditions
• Patients currently on chemotherapy or with other primary cancers requiring systemic or hepatic loco-regional treatment

• Patients who are clinically unstable, patients who are seriously or terminally ill with a life expectancy of less than 1 month, and patients whose clinical course are unpredictable; for example:

  • Patients on life support or in a critical care unit
  • Patients with unstable occlusive disease (e.g., crescendo angina)
  • Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia
  • Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] class IV)
  • Patients with recent cerebral hemorrhage
  • Patients who have undergone surgery within 24 hours prior to the study sonographic examination
• Patients with a history of anaphylactic allergy to Definity, manifested by one or more of the following symptoms: generalized urticaria, difficulty in breathing, swelling of the mouth and throat, hypotension, or shock
• Patients with congenital heart defects
• Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli
• Patients with respiratory distress syndrome
• Patients with thrombosis within the splenic vein

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: contrast-enhanced subharmonic ultrasound imaging; Patients receive perflutren lipid microspheres IV. After 15 minutes, patients receive perflutren lipid microspheres IV again over 5 minutes and undergo contrast-enhanced subharmonic ultrasound imaging over 60 minutes.	Drug: Perflutren Lipid Microspheres; Given IV; Other Names: Definity; Procedure: Contrast-Enhanced Subharmonic Ultrasound Imaging; Undergo contrast-enhanced subharmonic ultrasound imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Accuracy of Subharmonic Ultrasound Imaging Compared to Standard Ultrasound or Contrast Enhanced Magnetic Resonance Imaging (MRI)	The techniques will be compared using an analysis of variance (ANOVA) method (i.e., baseline ultrasound imaging, SHI, or MRI) as the dependent variable and outcome as the independent variables. Diagnostic accuracy of lesion identification as "no lesion seen", "definitely benign", "indeterminate" or "definitely malignant" based on independent reads by experience radiologists for SHI with and without contrast vs contrast-enhanced MRI (quantitative analysis). For qualitative analysis, digital images from the SHI imaging were reviewed by the independent radiologists for interpretation. Diagnostic accuracy reported as percentage of lesions correctly identified through SHI as compared to ultrasound or MRI as the gold standard.	Baseline scan to day of surgery
Accuracy of SHI Characterization Compared to the Risk of Malignancy Index	The ability of SHI to accurately characterize lesions as benign from malignant masses as compared to other imaging (ultrasound or MRI) and pathology will be analyzed using logistic regression and receiver operating characteristic (ROC) analyses.	Baseline scan to day of surgery

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: National Institutes of Health (NIH); Lantheus Medical Imaging
• Investigators: Principal Investigator: Flemming Forsberg, PhD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

• Thomas Jefferson University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): September 4, 2018
• Study Completion (Actual): September 4, 2018

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 29, 2017

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 16F.394; JT 9149 (Other Identifier: JeffTrial Number); R21CA190930 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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