Evaluation of Intraoperative Contrast Enhanced Ultrasound for the Identification of Pituitary Adenoma in Cushing's Disease Compared to Other Pituitary Tumors

This pilot and feasibility study aims to combine recent advances in ultrasound imaging, specifically an endonasal transducer array and contrast enhanced ultrasound, to offer an intraoperative image-guided solution for lesion-specific surgical resection to impact clinical outcome. Should this imaging approach help isolate specific lesions and prevent surgical resection of normal pituitary tissue in this first-in-humans study, then the results will provide clinical data for a much larger multi-center clinical trial.

Study Overview

• Status: Recruiting
• Conditions: Pituitary Adenoma; Cushing Disease
• Intervention / Treatment: Diagnostic test: Contrast enhanced pituitary magnetic resonance imaging (MRI); Diagnostic test: Contrast enhanced ultrasound; Diagnostic test: Non-Contrast Ultrasound

• Study Type: Observational
• Enrollment (Estimated): 110

Contacts and Locations

• Study Contact: Name: Neurologic Surgery Research Department; Phone Number: 507-293-7354; Email: Riess.Lesley@mayo.edu
• Study Contact Backup: Name: Ian Mark, MD; Phone Number: 61206 507-284-3211

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Neurologic Surgery Research Department; Phone Number: 507-293-7354

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with a pituitary adenoma or lesion that will undergo transnasal surgery

Description

For Contrast Based Protocol:

Inclusion Criteria:

• Diagnosis of Cushing disease or required resection for non-corticotroph adenomas
• Agree to transsphenoidal resection.

Exclusion Criteria:

• Patients who are unable to consent (or if their legal guardian/representative decline to consent)
• Patients who have known or suspected hypersensitivity to microbubble contrast agents or its components such as polyethylene glycol (PEG).
• Women of child-bearing potential with a positive pregnancy test prior to procedure.
• Patients who have right to left, bi-directional, or transient right to left cardiac shunts.
• Patients who have hypersensitivity to perflutren.

For Non-Contrast Based Protocol:

Inclusion Criteria:

• Patients undergoing any pituitary surgery with the study designated neurosurgeons.
• Patients whose procedures require the use of an intra-operative BK ultrasound without contrast.

Exclusion Criteria:

• Patients who are unable to consent (or if their legal guardian/representative decline to consent)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Contrast; Patients who are scheduled for transsphenoidal surgical resection for Cushing disease or transsphenoidal resection for non-corticotroph adenomas.	Diagnostic test: Contrast enhanced pituitary magnetic resonance imaging (MRI); Pre-operative contrast enhanced pituitary MRI and non-contrast intraoperative ultrasound.; Diagnostic test: Contrast enhanced ultrasound; Contrast enhanced intraoperative ultrasound imaging with Definity microbubbles that will be activated per the manufacturer specification and administered as a bolus of 0.2 mL of perflutren lipid microsphere intravenously followed by a 10 mL flush of saline. The pituitary will be imaged in the transverse plane for 2 minutes following this bolus. A repeat injection of the same ultrasound contrast dose and saline flush will be performed, and the pituitary will be imaged in the sagittal plane for 2 minutes.
Non-Contrast; Patients who are scheduled for a pituitary surgical procedure requiring an intra-operative ultrasound without contrast.	Diagnostic test: Non-Contrast Ultrasound; Intra-operative ultrasound without contrast for pituitary adenomas and MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scoring of non-contrast ultrasound images	Non-contrast ultrasound images will be evaluated by a board certified neuroradiologists with experience reviewing pituitary imaging. The ultrasound images will be scored on the identification, size, location, echogenicity, and enhancement of any potential pituitary lesions as well as a confidence level in identifying the adenoma (1-5 Likert scale) with 1 being non-diagnostic/poor and 5 being excellent/diagnostic quality.	Baseline
Scoring of contrast-enhanced ultrasound images	Contrast-enhanced ultrasound images will be evaluated by a board certified neuroradiologists with experience reviewing pituitary imaging. The ultrasound images will be scored on the identification, size, location, echogenicity, and enhancement of any potential pituitary lesions as well as a confidence level in identifying the adenoma (1-5 Likert scale) with 1 being non-diagnostic/poor and 5 being excellent/diagnostic quality.	Baseline
Scoring of pituitary MRI images	Preoperative Research Pituitary MRI images will be evaluated by a board certified neuroradiologists with experience reviewing pituitary imaging. The MRI images will be scored on the identification, size, location, echogenicity, and enhancement of any potential pituitary lesions as well as a confidence level in identifying the adenoma (1-5 Likert scale) with 1 being non-diagnostic/poor and 5 being excellent/diagnostic quality.	Baseline

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: GE Healthcare; Lantheus Medical Imaging; American Society of Head and Neck Radiology
• Investigators: Principal Investigator: Ian Mark, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: January 5, 2026
• First Posted (Actual): January 13, 2026

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Hyperpituitarism; Pituitary Diseases; Pituitary Neoplasms; Pituitary ACTH Hypersecretion
• Other Study ID Numbers: 23-009009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes