Functional Imaging of Baby Brains

Hypoxic-Ischemic Encephalopathy Clinical Trial

— FIBB  

Official title:

A Prospective Feasibility Study to Derive Novel Imaging Biomarker of Perinatal Brain Injury Based on Bedside Diffuse Optical Tomography in Neonates

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05514665
• Other study ID #: NIF-22535
• Status: Not yet recruiting
• Start date: March 2024
• Est. completion date: April 1, 2026

Study information

• Verified date: March 2024
• Source: Hamilton Health Sciences Corporation
• Contact: Ipsita Goswami, MD, MSc
• Phone: 9055212100
• Email: goswamii[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Infants are at risk of developing motor and cognitive neurodevelopmental disabilities as a sequelae to hypoxic-ischemic brain injury during the perinatal period. It is an ongoing challenge to predict the severity and extent of future developmental impairment during the neonatal period. This study will help test the feasibility of conducting a large-scale study that evaluates the role of diffuse optical tomography as a bedside neuroimaging tool in complementing the prognostic value of conventional and diffusion weighted MRI for predicting neurodevelopmental outcome in neonates with perinatal hypoxic-ischemic brain injury.

Description:

Perinatal hypoxic-ischemic brain injury is a major cause of childhood disabilities including cerebral palsy, developmental delay, attention deficits, behavioral concerns, and learning disabilities. Accurate prediction of neurologic deficits in the neonatal period is difficult, especially the ability to predict later cognitive impairment and socio-emotional challenges. Many of these disabilities are manifested at school age when the child is beyond the critical time window of early brain development. Prognostic tools that help to identify neonates most at risk of developing neuro-deficits after perinatal asphyxia are needed and would enable targeted early intervention in infancy, when the developing brain is most amenable to positive changes and improve neurologic outcome. Currently, structural changes observed in MRI brain images are used to predict outcome. However, this modality does not provide information on brain function, nor is it a good prognostic marker of future neurocognitive outcome. Functional MRI (fMRI) is time-consuming and not commonly a part of clinical assessment of the neonates. Diffuse Optical Tomography (DOT) using near-infrared light has been applied in research settings to map the functional connections between key brain regions. This technology, although reported to be safe and reliable in small studies, has not been widely used in the neonatal clinical setting. This approach is based on the synchronous, spontaneous fluctuations of cerebral blood flow in different regions of the brain that are functionally, yet not necessarily anatomically connected. DOT combines the portability and cap-based scanning of EEG with spatial resolution high enough to create detailed cortical maps of the neonatal brain. Compared to MRI and fMRI brain imaging, DOT is portable, light weight, has high body motion tolerance, does not produce noise and does not require infant sedation. It has the potential to be a powerful bedside non-invasive clinical neuroimaging tool. Currently, the predictive accuracy of DOT based neonatal brain connectivity measures in prognosticating early childhood is unknown. This study aims to assess the feasibility of the processes that are key to the success of a large-scale prospective study aimed at investigating the prognostic value of bedside DOT derived biomarker in neonatal brain after perinatal hypoxic-ischemic brain injury.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 25
• Est. completion date: April 1, 2026
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 7 Days

Eligibility

Inclusion Criteria:

• Newborns admitted to the McMaster Children's Hospital Neonatal Intensive Care Unit with the diagnosis of hypoxic-ischemic encephalopathy will be considered for this study
• Gestational age of 35 weeks or greater
• Birth weight more than 1.8 Kg

Exclusion Criteria:

• suspected or confirmed congenital brain malformations
• chromosomal anomalies
• inborn errors of metabolism
• congenital TORCH infections
• neonatal encephalopathy other than hypoxic-ischemic encephalopathy
• confirmed meningitis

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypoxia
• Hypoxia Ischemia, Cerebral
• Hypoxia Neonatal
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy
• Ischemia

Intervention

Device:
• Diffuse Optical Tomography
Neonates once hemodynamically stable will undergo diffuse optical tomography measurements of functional brain connectivity at the bedside within 3-7 days after birth.

Locations

Country	Name	City	State
Canada	McMaster Childrens Hospital	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (10)

Doria V, Beckmann CF, Arichi T, Merchant N, Groppo M, Turkheimer FE, Counsell SJ, Murgasova M, Aljabar P, Nunes RG, Larkman DJ, Rees G, Edwards AD. Emergence of resting state networks in the preterm human brain. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20015-20. doi: 10.1073/pnas.1007921107. Epub 2010 Nov 1. — View Citation

Ferradal SL, Liao SM, Eggebrecht AT, Shimony JS, Inder TE, Culver JP, Smyser CD. Functional Imaging of the Developing Brain at the Bedside Using Diffuse Optical Tomography. Cereb Cortex. 2016 Apr;26(4):1558-68. doi: 10.1093/cercor/bhu320. Epub 2015 Jan 16. — View Citation

Fransson P, Skiold B, Horsch S, Nordell A, Blennow M, Lagercrantz H, Aden U. Resting-state networks in the infant brain. Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15531-6. doi: 10.1073/pnas.0704380104. Epub 2007 Sep 18. — View Citation

Gao W, Alcauter S, Elton A, Hernandez-Castillo CR, Smith JK, Ramirez J, Lin W. Functional Network Development During the First Year: Relative Sequence and Socioeconomic Correlations. Cereb Cortex. 2015 Sep;25(9):2919-28. doi: 10.1093/cercor/bhu088. Epub 2014 May 8. — View Citation

Gollenberg AL, Lynch CD, Jackson LW, McGuinness BM, Msall ME. Concurrent validity of the parent-completed Ages and Stages Questionnaires, 2nd Ed. with the Bayley Scales of Infant Development II in a low-risk sample. Child Care Health Dev. 2010 Jul;36(4):485-90. doi: 10.1111/j.1365-2214.2009.01041.x. Epub 2009 Dec 16. — View Citation

Lee CW, Cooper RJ, Austin T. Diffuse optical tomography to investigate the newborn brain. Pediatr Res. 2017 Sep;82(3):376-386. doi: 10.1038/pr.2017.107. Epub 2017 May 31. — View Citation

Liao SM, Gregg NM, White BR, Zeff BW, Bjerkaas KA, Inder TE, Culver JP. Neonatal hemodynamic response to visual cortex activity: high-density near-infrared spectroscopy study. J Biomed Opt. 2010 Mar-Apr;15(2):026010. doi: 10.1117/1.3369809. — View Citation

Niu H, Li Z, Liao X, Wang J, Zhao T, Shu N, Zhao X, He Y. Test-retest reliability of graph metrics in functional brain networks: a resting-state fNIRS study. PLoS One. 2013 Sep 9;8(9):e72425. doi: 10.1371/journal.pone.0072425. eCollection 2013. — View Citation

Smyser CD, Wheelock MD, Limbrick DD Jr, Neil JJ. Neonatal brain injury and aberrant connectivity. Neuroimage. 2019 Jan 15;185:609-623. doi: 10.1016/j.neuroimage.2018.07.057. Epub 2018 Jul 27. — View Citation

Zhang X, Toronov V, Webb A. Simultaneous integrated diffuse optical tomography and functional magnetic resonance imaging of the human brain. Opt Express. 2005 Jul 11;13(14):5513-21. doi: 10.1364/opex.13.005513. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Consent rate	An eligible patient (parents or substitute decision makers) consents to the study	12 months
Primary	Rate of completion of study intervention	An enrolled patient receives DOT measurements taken within 7 days of life	12 months
Primary	Rate of successful data acquisition	An enrolled patient completes resting state DOT data acquisition within 45 mins without sedation	12 months
Primary	Rate of developmental follow up	An enrolled patient is assessed for neurological outcome at the age of 6 months and 12 months	12 months
Secondary	Resting state connectivity measures	Strength of network connectivity in pre-identified brain regions i.e somatosensory cortex and auditory cortex	12 months
Secondary	First time-point developmental assessment	Assessed by parent-filled questionnaire using Ages and Stages Questionnaire-3 rd edition. Total score in each domain (Cognitive, Gross motor, Fine motor, Problem solving, Personal social) ranges from 0-60. Higher score is better.	6 months post menstrual age
Secondary	Second time-point developmental assessment	Assessed by parent-filled questionnaire using Ages and Stages Questionnaire-3 rd edition. Total score in each domain (Cognitive, Gross motor, Fine motor, Problem solving, Personal social) ranges from 0-60. Higher score is better	12 months post menstrual age