SHAPE for ICP Assessment

Subharmonic Aided Pressure Estimation (SHAPE) for Intracranial Pressure (ICP) Assessment

The Subharmonic Aided Pressure Estimation (SHAPE) technique is a noninvasive ultrasound-based imaging technique that can estimate ambient pressure using subharmonic emissions from ultrasound contrast agents. Ultrasound contrast agents are encapsulated microbubbles (mean diameter < 8 µm) with a lipid, protein, or polymer shell that traverse the entire vasculature. When the contrast microbubbles are insonated with relatively high acoustic pressures (>100-150 kPa), these microbubbles act as nonlinear oscillators yielding energy components in the received echo signals at frequencies ranging from the subharmonic (half of transmit frequency) to higher harmonics and even ultraharmonics. Based on empirical evidence, the subharmonic signal exhibits a sigmoidal relationship with incident acoustic pressure i.e., subharmonic signal can be divided into occurrence, growth and saturation stages. In the growth stage, the subharmonic signal has shown sensitivity to ambient pressure characterized by an inverse linear relationship between subharmonic signal and ambient pressure changes. This inverse linear relationship forms the basis for the SHAPE technique. Several pre-clinical and clinical studies have been conducted to utilize the SHAPE technique for in vivo pressure estimation e.g., to diagnose portal hypertension, to estimate intra-cardiac pressures and to determine interstitial fluid pressures. The core imaging mode underpinning the SHAPE technology (subharmonic imaging) is now available on some commercial scanners. In the proposed pilot study, the SHAPE technique will be leveraged for monitoring intracranial pressure (ICP). The use of SHAPE technique for the ophthalmic artery could potentially provide an accurate noninvasive method of measuring ICP in patients with idiopathic intracranial hypertension (IIH) and other conditions of raised ICP, which would revolutionize the field.

Study Overview

• Status: Completed
• Conditions: Lumbar Puncture
• Intervention / Treatment: Drug: Perflutren lipid microsphere

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Scheduled for lumbar puncture to assess ICP pressures
• Age over 18.

Exclusion Criteria:

• Pregnant or nursing
• Medically unstable
• Allergy to any components of Definity.
• Unable to provide written informed consent

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: SHAPE for ICP diagnosis	Drug: Perflutren lipid microsphere; Definity (Lantheus Medical Imaging, N Billerica, MA) in 25 mL of saline infused for up to 6 minutes; Other Names: Definity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparing SHAPE to lumbar puncture pressure measurements	Use of the SHAPE technique for measuring ophthalmic artery pressure in patients undergoing lumbar puncture for suspected idiopathic intracranial hypertension and compare the SHAPE data with pressures obtained using lumbar puncture (reference standard)	1 year

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2024
• Primary Completion (Actual): July 31, 2025
• Study Completion (Actual): August 26, 2025

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: perflutren
• Other Study ID Numbers: 2023-2116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data generated and/or analyzed during this study are available from the PI upon request.
• IPD Sharing Time Frame: 12 months after completion of the study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

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.: No