Feasibility and Validity of Ultra- Low-Field MRI for Measurement of Regional Infant Brain Volumes in Structures Associated with Antenatal Maternal Anemia

Introduction The availability of ultra- low-field (ULF) magnetic resonance imaging (MRI) has the potential to improve neuroimaging accessibility in low-resource settings. However, the utility of ULF MRI in detecting child brain changes associated with anemia is unknown. Aim The aim of this study was to assess the comparability of 3T high-field (HF) and 64mT ULF volumes in infants for brain regions associated with antenatal maternal anemia.

This neuroimaging sub-study is nested within Khula South Africa, a population-based birth cohort. Pregnant women were enrolled antenatally and postnatally, and mother-child dyads (n = 394) were followed prospectively at approximately 3, 6, 12 and 18 months. A sub-group of infants was scanned on 3T and 64mT MRI systems across study visits and images were segmented using MiniMORPH. Correlations and concordance coefficients were used to cross-validate HF and ULF infant brain volumes for the caudate nucleus, putamen, and corpus callosum.

78 children (53.85% male) had paired HF (Mean [SD] age = 9.64 [5.26] months) and ULF (Mean [SD] age = 9.47 [5.32] months) datasets. Results indicated strong agreement between systems for intracranial volume (ICV; r = 0.96, ρccc = 0.95), and brain regions of interest in anemia including the caudate (r = 0.89, ρccc = 0.86), putamen (r = 0.97, ρccc = 0.96), and corpus callosum (r = 0.87, ρccc = 0.79).

This cross-validation study demonstrates excellent correspondence between 3T and 64mT volumes for infant brain regions implicated in antenatal maternal anemia. Findings validate the use of ULF MRI for paediatric neuroimaging on anemia in Africa. HIGHLIGHTS This cross-validation study is the first to compare HF and ULF volume estimates for infant brain regions previously found to be associated with antenatal maternal anemia within the first two years of life. Key findings of this research demonstrate linear associations and strong agreement between HF and ULF volume estimates for the caudate nucleus, putamen, and corpus callosum in infants between 3-18 months of age. Improved correspondence between HF and ULF MRI was observed in older infants, particularly for basal ganglia structures. These novel findings validate the use of ULF MRI for paediatric neuroimaging work on antenatal maternal anemia and other prevalent health priorities in low- and middle-income countries. GRAPHICAL ABSTRACT This cross-validation study assessed the comparability of high-field (3T) and ultra- low-field (64mT) volumes in infants for brain regions associated with antenatal maternal anemia. Key findings demonstrated strong agreement between HF and ULF volume estimates for the caudate nucleus, putamen, and corpus callosum in infants between 3-18 months of age. Competing Interest Statement The authors have declared no competing interest. Funding Statement The Khula birth cohort was supported by the Wellcome Leap 1kD programme (The First 1000 Days; 222076/Z/20/Z). J.E. Ringshaw is supported by a Wellcome Trust International Training Fellowship (224287/Z/21/Z). The anemia analyses were also funded by the Gates Foundation (INV-023509) awarded to K.A. Donald. S.C.R. Williams is supported by the Bill and Melinda Gates Foundation (INV-047888) and the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC). D.J. Stein is supported by the South African Medical Research Council (SAMRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Khula South Africa birth cohort study received ethical approval from the University of Cape Town Human Ethics Research Committee (HREC; 666/2021; 782/2022). All mothers provided written informed consent for cohort participation at Khula enrolment, and for their children to participate in study-specific procedures across timepoints. Given the longitudinal nature of the cohort, study consent is obtained from mothers annually for this cohort. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data used for these analyses have been deposited in ZivaHub Open, a public repository. This information can be found at the following DOI: https://doi.org/10.25375/uct.29197649.v1