Novel User-friendly Ultrasound Methods for Monitoring and Prevention of Cerebral Hypoxia

Project Information

US-CHIMP

Grant agreement ID: 101105524

DOI

10.3030/101105524

Project closed

EC signature date 22 March 2023

Start date 5 June 2023

End date 4 June 2025

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 172 750,08

Coordinated by

ACCADEMIA EUROPEA DI BOLZANO
Italy

Periodic Reporting for period 1 - US-CHIMP (Novel User-friendly Ultrasound Methods for Monitoring and Prevention of Cerebral Hypoxia)

Reporting period: 2023-06-05 to 2025-06-04

Summary of the context and overall objectives of the project

The US-CHIMP (Ultrasound Cerebral Hypoxia Imaging for Monitoring and Prevention) project addresses a critical healthcare challenge: the timely and accurate detection of cerebral hypoxia low oxygen levels in the brain, which can lead to permanent neurological damage. Cerebral hypoxia affects approximately half of critically ill patients but studying these conditions directly in intensive care settings is complicated due to patients' unstable health. Instead, US-CHIMP utilizes the unique environment of high-altitude exposure, where reduced oxygen levels naturally simulate conditions similar to clinical hypoxia, enabling safe investigation in healthy volunteers.
Currently, the non-invasive techniques available to detect cerebral hypoxia either demand highly skilled personnel, involve significant observer variability, or lack clearly established diagnostic thresholds. There is an urgent need for accessible, user-friendly, and reliable tools to monitor and diagnose cerebral hypoxia effectively, particularly in challenging environments such as mountain rescue operations and remote healthcare settings. Ultrasound is portable and can be used in the field and at the bedside.
The main goal of US-CHIMP is to develop a proof-of-concept ultrasound-based diagnostic method. This involves two primary innovative approaches:
1. Using 3D ultrasound imaging to measure the volume of the optic nerve sheath as an indirect marker of intracranial pressure, a critical indicator often linked to cerebral hypoxia.
2. Applying Wave Intensity Analysis (WIA) to the internal carotid and vertebral arteries to detect changes in cerebral blood flow dynamics as an indirect measure of brain oxygenation.
The project comprises three core objectives:
• Developing a reliable, semi-automated method for volumetric ultrasound assessment of the optic nerve sheath.
• Establishing Wave Intensity Analysis techniques to characterize cerebral vascular changes due to hypoxia.
• Validating these methods through controlled studies involving human volunteers exposed to simulated high-altitude conditions in the state-of-the-art environmental chamber.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The US-CHIMP project successfully conducted several significant activities and achieved important milestones, structured around three key technical and scientific work packages:

Work Package 1: 3D Ultrasound Imaging Methods of Optic Nerve Sheath Diameter
• Developed and fully validated a novel, semi-automated 3D ultrasound technique for accurate quantification of the optic nerve sheath, a critical indicator of intracranial pressure.
• Created robust software and algorithms for freehand 3D ultrasound imaging, significantly reducing variability and user dependence compared to traditional 2D techniques.
• Demonstrated that 3D measurements are independent of observer alignment and geometric assumptions, thereby improving the accuracy, reliability, and reproducibility of optic nerves sheath assessments.
• Introduced new diagnostic markers such as optic nerve sheath thickness, uniformity, and eccentricity, with thickness identified as the most sensitive indicator of intracranial pressure changes.
• Achieved full validation of the method, with outcomes currently under peer review at the highly-ranked journal Investigative Radiology and scheduled presentations at IEEE International Ultrasound Symposium 2025.

Work Package 2: Wave Intensity Analysis (WIA) and Hemodynamic Model of Cerebral Hypoxia
• Developed a computational model (1D Vascular Network Simulator) for simulating cerebrovascular hemodynamics under hypoxic conditions
• Created algorithms and a graphical user interface for real-time capture and analysis of cerebral blood flow and vessel diameter data.
• Conducted preliminary human studies showing WIA’s potential in detecting cerebral vascular changes caused by hypoxia, hypercapnia, and cold exposure.
• Presented initial findings at the Danish Cardiovascular Academy Winter Meeting (2025), highlighting WIA’s effectiveness in identifying physiological responses indicative of cerebrovascular stress.
Work Package 3: Validation in Human Subjects
• Successfully completed human volunteer studies validating developed techniques under controlled hypoxic conditions at the terraXcube facility.
• Led and collaborated in multiple studies to evaluate cerebral responses to hypoxia, cold, and combined stressors.
• Identified critical limitations in existing literature regarding 2D ONSD measurements, emphasizing the need for 3D imaging and automated measurement protocols.
• Developed a comprehensive understanding of the interaction between hypoxia and cold exposure, providing critical insights into physiological mechanisms underlying cerebral hypoxia and associated conditions such as Acute Mountain Sickness.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

These achievements collectively represent a substantial advancement in non-invasive cerebral hypoxia monitoring technologies, significantly enhancing diagnostic reliability and clinical applicability for critical care and high-altitude medicine.

Results Beyond the State of the Art
• US-CHIMP has significantly advanced non-invasive diagnostics by demonstrating superior 3D ultrasound methodologies that surpass current 2D measurement capabilities, ensuring higher measurement fidelity.
• The project introduced Wave Intensity Analysis as a novel technique for assessing cerebral vascular responses.
Potential Impacts and Key Needs for Further Uptake:
• US-CHIMP techniques offer considerable potential to transform patient care and clinical decision-making in emergency medicine, intensive care, and remote healthcare settings.
• Further clinical research, broader validation studies, and demonstrations are crucial to facilitate integration into routine clinical practice and are currently in planning.
• Access to markets, targeted commercialisation strategies, and dedicated financial support will be essential for successful technology transfer.

Healthy volunteers exposed to cold conditions during the experiment study

Measurement of the optic nerve sheath during an experimental study

GUI to capture simultaneous velocity and diameter and to automate WIA in real time

Simulated ultrasound bi-plane and 3D volumes from MRI data

Example of a 3D scan of the optic nerve sheath with 3D freehand ultrasound

61 artery model of the cerebral circulation