Magnetic Resonance Imaging and Spectroscopy Biomarkers of Neonatal Hypoxic Ischemic Encephalopathy

Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) Biomarkers of Neonatal Hypoxic Ischemic Encephalopathy

Neonatal hypoxic ischemic encephalopathy (HIE) is a serious neurological condition characterised by acute or subacute brain injury arising from perinatal hypoxia. HIE is thought to affect approximately 0.2% of live births, and is associated with a high risk of mortality or long-term neurological disability.

Accurate biomarkers for long-term neuro-developmental outcome following HIE are extremely important both for clinical management and the evaluation of therapeutic approaches. According to a recent meta-analysis, the ratio of the cerebral concentrations of lactate and N-acetyl aspartate (NAA), two neuro-metabolites detectable with magnetic resonance spectroscopy (MRS), currently represents the most accurate prognostic indicator of outcome following HIE. However, for various technical reasons standard MRS methods do not offer optimal sensitivity for detecting lactate, which may potentially be improved with a custom lactate editing MRS sequence. In addition, while perfusion has also been suggested as a potential biomarker for neuro-developmental outcome following HIE, due to a paucity of MR perfusion imaging studies in neonates, the prognostic accuracy of perfusion MR measures has not been evaluated in comparison with more established MR biomarkers. The aims of this study are:

1. to evaluate the relative sensitivity of a custom lactate editing MRS pulse sequence (specialist software) relative to the standard point resolved (PRESS) MRS sequence for detecting lactate in neonates with suspected HIE.
2. to evaluate the sensitivity and specificity of MR perfusion measures in comparison to MRS measures as predictors of neuro-developmental outcome at 2 years.

Study Overview

• Status: Completed
• Conditions: Hypoxic Ischemic Encephalopathy

• Study Type: Observational
• Enrollment (Actual): 59

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8032
    • University Children's Hospital Zurich, MRI Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 weeks (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

neonates with suspected hypoxic ischemic encephalopathy

Description

Inclusion Criteria:

• Newborn infants (born at >36 weeks) with suspected perinatal asphyxia. Written informed consent from both parents.

Exclusion Criteria:

• Prematurity (born at < 36 weeks). Lack of written informed consent from both parents.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
neonates with perinatal asphyxia; neonates with suspected perinatal asphyxia (HIE)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sensitivity of lactate editing MR spectroscopy sequence (software) relative to that of the standard MR spectroscopy sequence.	The primary end-point will be reached when lactate and perfusion data have been collected from 30 neonates. The efficacy of the custom-MRS lactate editing sequence will be assessed relative to that of the standard MRS sequence for the detection of lactate (by comparing the lactate concentration (in mM) measured from the lactate edited MR spectra to that measured from the standard MR spectra).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prognostic accuracy (sensitivity and specificity) of MRI and MRS for predicting motor outcome at age 2	The secondary end-point will be reached upon completion of a neurological development assessment at the age of 2 years. Patients will be classified as having a good or poor outcome based on their motor skills at age 2, and the prognostic accuracy (eg sensitivity and specificity for predicting neuromotor outcome) of the standard and new MRI and MRS sequences will be assessed.	3 years

Collaborators and Investigators

• Sponsor: University Children's Hospital, Zurich
• Investigators: Principal Investigator: Ruth L O'Gorman, phD, University Children's Hospital Zurich, MRI Center

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): July 9, 2019
• Study Completion (ACTUAL): July 9, 2019

Study Registration Dates

• First Submitted: November 21, 2011
• First Submitted That Met QC Criteria: November 24, 2011
• First Posted (ESTIMATE): November 29, 2011

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; magnetic resonance spectroscopy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: CIV-11-11-002981

Plan for Individual participant data (IPD)

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