TY - JOUR
T1 - Development of neonatal-specific sequences for portable ultralow field magnetic resonance brain imaging
T2 - a prospective, single-centre, cohort study
AU - UNITY Consortium
AU - Cawley, Paul
AU - Padormo, Francesco
AU - Cromb, Daniel
AU - Almalbis, Jennifer
AU - Marenzana, Massimo
AU - Teixeira, Rui
AU - Deoni, Sean C.
AU - Ljungberg, Emil
AU - Bennallick, Carly
AU - Kolind, Shannon
AU - Dean, Doug
AU - Pepper, Michael S.
AU - Sekoli, Lydia
AU - De Canha, Alexica
AU - Van Rensburg, Jeanne
AU - Jones, Derek K.
AU - Bourke, Niall
AU - Sabir, Hemmen
AU - Lecurieux Lafayette, Samson
AU - Uus, Alena
AU - O'Muircheartaigh, Jonathan
AU - Williams, Steven C.R.
AU - Counsell, Serena J.
AU - Arichi, Tomoki
AU - Rutherford, Mary A.
AU - Hajnal, Joseph V.
AU - Edwards, A. David
N1 - Funding Information:
The Bill and Melinda Gates Foundation, the MRC, the Wellcome/EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas’ and South London & Maudsley NHS Foundation Trusts and King's College London.This work is supported by the Bill and Melinda Gates Foundation (Ultralow field Neuroimaging In The Young: INV-005798), the Wellcome/EPSRC Centre for Medical Engineering [WT 203148/Z/16/Z], the Medical Research Council Centre for Neurodevelopmental Disorders [MR/N026063/1], MRC Clinician Scientist Fellowship & Translation Support Awards [MR/P008712/1] & [MR/V036874/1], and by the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas’ and South London & Maudsley NHS Foundation Trusts and King's College London. We would like to thank the infants and families who participated in this research. We also thank the many research and clinical staff at the Centre for the Developing Brain, King's College London, and Evelina London Children's Hospital, for their enthusiasm, support, and dedicated work. We thank the reviewers of our submission whose expert review has improved this work considerably. Sections of this work have previously been presented at: Neonatal Society Autumn Meeting 2021, ISMRM Workshop on Low Field MRI 2022, Joint Annual Meeting of the ISMRM-ESRMB & ISMRT 2022 & 2023, Neonatal Society Summer Meeting 2022, 12th International Congress of UENPS 2022, BAPM Annual Conference 2022 and the Royal College of Paediatrics and Child Health Annual Conference 2023. T1 mapping data of 28 infants included within this paper are published in Magnetic Resonance in Medicine 2022.20
Funding Information:
This work is supported by the Bill and Melinda Gates Foundation (Ultralow field Neuroimaging In The Young: INV-005798), the Wellcome / EPSRC Centre for Medical Engineering [WT 203148/Z/16/Z ], the Medical Research Council Centre for Neurodevelopmental Disorders [ MR/N026063/1 ], MRC Clinician Scientist Fellowship & Translation Support Awards [ MR/P008712/1 ] & [ MR/V036874/1 ], and by the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy’s and St Thomas’ and South London & Maudsley NHS Foundation Trusts and King's College London .
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/11
Y1 - 2023/11
N2 - Background: Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies. Methods: Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested. Findings: Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40+2 weeks (range: 31+3–53+4). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle. Interpretation: On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted. Funding: The Bill and Melinda Gates Foundation, the MRC, the Wellcome/ EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas’ and South London & Maudsley NHS Foundation Trusts and King's College London.
AB - Background: Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies. Methods: Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested. Findings: Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40+2 weeks (range: 31+3–53+4). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle. Interpretation: On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted. Funding: The Bill and Melinda Gates Foundation, the MRC, the Wellcome/ EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas’ and South London & Maudsley NHS Foundation Trusts and King's College London.
KW - Intensive care
KW - Low field
KW - Magnetic resonance imaging
KW - Neonatal
KW - Portable
UR - http://www.scopus.com/inward/record.url?scp=85175833822&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2023.102253
DO - 10.1016/j.eclinm.2023.102253
M3 - Article
AN - SCOPUS:85175833822
SN - 2589-5370
VL - 65
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 102253
ER -