Kadi Vaher¹, Paola Galdi¹, Manuel Blesa Cabez¹, Gemma Sullivan¹, Gill Black¹, David Q Stoye¹, Alan J Quigley², Michael J Thrippelton³, Simon R Cox⁴, Mark E Bastin³, Debby Bogaert⁵, and James P Boardman^1
1MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom, ²Department of Paediatric Radiology, Royal Hospital for Sick Children, Edinburgh, United Kingdom, ³Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom, ⁴Lothian Birth Cohort Studies group, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom, ⁵Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom

Preterm birth associates with diffuse white matter dysmaturation, which is linked to neurocognitive impairment. We applied principal component analysis to tract-averaged diffusion tensor (DTI) and neurite orientation and density imaging (NODDI) measures to derive single- and multimodal general factors describing neonatal white matter microstructure. We report substantial shared variance of DTI and NODDI metrics across 16 white matter tracts and between the different metrics; the derived general factors associate with preterm birth. These results suggest that general factors are efficient markers of generalised white matter microstructure in early life, and are useful for investigating the determinants of white matter development.

Yao Sui^1,2, Onur Afacan^1,2, Ali Gholipour^1,2, and Simon K Warfield^1,2
1Harvard Medical School, Boston, MA, United States, ²Boston Children's Hospital, Boston, MA, United States

Neonatal brain MRI is a resolution-critical task due to the small brain of neonates. Among post-acquisition resolution-enhancement techniques, deep learning has shown promising results. Most state-of-the-art deep learning-based super-resolution methods work on 2D slices, so ignore the 3D nature of the brain anatomy. Learning on 3D images requires large-scale training datasets of high-resolution volumes that are, unfortunately, difficult to acquire. We developed a methodology that enables learning 3D gradient structures from 2D slices for an individual subject without the need for large, auxiliary high-resolution datasets. Experiments on clinical data from ten neonates demonstrate our approach outperformed state-of-the-art MRI super-resolution methods.

Moyoko Tomiyasu^1,2, Jun Shibasaki³, Yasuhiko Terada⁴, Katsuaki Toyoshima³, Tatsuya Higashi¹, Takayuki Obata¹, and Noriko Aida^2
1Department of Molecular Imaging and Theranostics, National Institute for Quantum and Radiological Science and Technology, Chiba, Japan, ²Department of Radiology, Kanagawa Children’s Medical Center, Yokohama, Japan, ³Department of Neonatology, Kanagawa Children’s Medical Center, Yokohama, Japan, ⁴Institute of Applied Physics, University of Tsukuba, Tsukuba, Japan

We examined brain temperatures of 81 neonates with hypoxic-ischemic encephalopathy during and/or after hypothermia therapy. The brain temperature was obtained from magnetic resonance spectroscopy data (3T). The subjects also had a neurological developmental test at the age of 18–22 months, and were divided into favorable and adverse outcome groups. Brain temperatures for each outcome were significantly lower during hypothermia compared with those after hypothermia. Although the poor prognosis group tended to have a large dispersion of brain temperature after hypothermia, there was no significant difference in brain temperature between the favorable and adverse outcome groups.

Julia E. Kline¹, Weihong Yuan¹, Karen Harpster¹, and Nehal A. Parikh^1
1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Very preterm (VPT) infants are at risk for serious motor impairments, including cerebral palsy (CP). Motor interventions are most effective if delivered early, but early accurate biomarkers of CP are lacking. In a cohort of 345 VPT infants, we extracted cortical morphometrics and brain volumes from term structural MRI and applied graph theoretical methods to term diffusion MRI connectomes. We observed consistent negative associations between early CP risk and cortical surface area, subcortical volumes, and graph metrics, including global efficiency and local efficiency of motor regions. These early biomarkers enhance our understanding of VPT motor impairments and may predict CP.

Hillary Idogwu¹, Magdalena Sokolska², Pang Raymand ³, Saiful Islam⁴, Christopher Meehan ³, Adnan Avdic-Belltheus ³, Kathryn Marinello ³, Ingran Lingam ³, Tatenda Mutshiya ³, Alan Bainbridge ², Nikki Robertson ³, David Thomas¹, and Xavier Golay^1
1Brain Repair and Rehabilitation, Institute of Neurology, UCL Queen Square Institute of Neurology, London, United Kingdom, ²Medical Physics and Biomedical Engineering, UCLH NHS Foundation Trust, London, United Kingdom, ³Neonatology, UCL EGA Institute for Women's Health, London, United Kingdom, ⁴UCL Queen Square Institute of Neurology, London, United Kingdom

Despite therapeutic hypothermia, some survivors of neonatal encephalopathy (NE) still have adverse outcomes. Surrogate outcome measures or biomarkers are needed for early detection of babies with adverse outcome so that adjunct therapies can be considered. Basal ganglia and thalamus (BGT) lactate/ N-Acetyl-Aspartate (Lac/NAA) peak area ratio acquired with proton magnetic resonance spectroscopy (MRS) is a reliable predictor of developmental outcome at two years. Cerebral blood flow (CBF) changes in parallel with the metabolic changes after hypoxia ischaemia (HI). We hypothesised that the combination of CBF with BGT Lac/NAA would be more closely associated with quantitative cell death than either alone. 

Tingting Liu¹, Weihao Zheng¹, Yuqing You², Ying Lv², Weijun Chen², Zhiyong Zhao¹, Fusheng Gao², Hongxi Zhang², Chai Ji², and Dan Wu^1
1ZheJiang University, Hangzhou, China, ²Children's Hospital, ZheJiang University School of Medicine, Hangzhou, China

The present study aimed to investigate brain asymmetry of healthy preterm-born infants within half-year-old using high angular resolution diffusion MRI. ROI-based analysis revealed most brain regions showed significant asymmetry and the asymmetry changed with brain development. The MD-based lateralization index showed an center-versus-peripheral pattern with remarkable lateralization in the posterior cortex. Moreover, in contrast to the adult brain, we found a rightward asymmetry in language processing regions and leftward asymmetry in visuospatial processing regions. Besides, consistent leftward lateralization in white matter was observed at both ROI-based and fixel-based analysis. These findings advanced our understanding of brain asymmetry during early development.

Jerod M Rasmussen¹, Alice M Graham², Pathik D Wadhwa¹, Sonja Entringer³, Martin Styner⁴, Beatriz Luna⁵, Thomas G O'Connor⁶, Damien A Fair⁷, and Claudia Buss^3
1UC Irvine, Irvine, CA, United States, ²Oregon Health Sciences University, Portland, OR, United States, ³Charité – Universitätsmedizin Berlin, Berlin, Germany, ⁴University of North Carolina, Chapel Hill, NC, United States, ⁵University of Pittsburgh, Pittsburgh, PA, United States, ⁶University of Rochester, Rochester, NY, United States, ⁷University of Minnesota, Minneapolis, MN, United States

We leverage an exemplar relationship (FA_WM vs. postmenstrual age [PMA]) to quantify the benefits conferred by adjustment for QC measures in a multi-site infant DWI study. Data was preprocessed using a common pipeline (dHCP) and the FA_WM-PMA association tested without and with controlling for SNR, CNR and mean FD. All three QC measures were broadly associated with FA_WM within sites. Within and across sites, inclusion of QC measures greatly increased FA_WM variance explained by PMA. Accounting for QC measures results in an improved capability for identifying reproducible small-effect size relationships in large multi-site infant imaging studies.

Wenchuan Wu¹, Luke Baxter^1,2, Eleri Adams^2,3, Foteini Andritsou², Matteo Bastiani^1,4,5, Ria Evans Fry², Robert Frost^6,7, Sean Foxley⁸, Chris Gallagher¹, Fiona Moultrie², Vaneesha Monk², David Andrew Porter⁹, Anthony Price^10,11, Sebastian W Rieger^1,12, Michael Sanders¹, Anthony David Edwards¹¹, Joseph V Hajnal^10,11, Rebeccah Slater*^1,2, and Karla L Miller*^1
1Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ²Department of Paediatrics, University of Oxford, Oxford, United Kingdom, ³Newborn Care Unit, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom, ⁴Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ⁵NIHR Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom, ⁶Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ⁷Department of Radiology, Harvard Medical School, Boston, MA, United States, ⁸Department of Radiology, University of Chicago, Chicago, IL, United States, ⁹Imaging Centre of Excellence, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom, ¹⁰Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London, United Kingdom, ¹¹Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London, United Kingdom, ¹²Department of Psychiatry, University of Oxford, Oxford, United Kingdom

In this work, we develop a 7T experimental platform to acquire high resolution diffusion MRI images in unfixed post-mortem infant brains. Here we present results from a first infant. The post-mortem structural images demonstrate superior SNR and improved depiction of small structures than age-matched low-resolution in vivo data. The post-mortem diffusion MRI images show sufficient SNR to support the considerably smaller voxel volume compared to in vivo. The high spatial resolution of the post-mortem data enables the depiction of brain features (e.g., cortical radiality, subplate organization) that are less prominent in low-resolution in vivo data.

dejun she¹, dairong cao¹, shan lin¹, zhongshuai zhang², and Robert Grimm^3
1The First Affiliated Hospital of Fujian Medical University, Fujian Fuzhou, China, ²SIEMENS healthcare diagnostic imaging, Shanghai, Pudong, Zhouzhu Highway 278, China, ³SIEMENS Healcare, Erlangen, Germany

To explore the correlations between parameters derived from conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) with histopathologic features of pediatric intracranial tumors.

Sayo Otani¹, Yasutaka Fushimi¹, Satoshi Nakajima¹, Akihiko Sakata¹, Takuya Hinoda¹, Sonoko Oshima¹, Krishna Pandu Wicaksono¹, Hiroshi Tagawa¹, Yang Wang¹, and Yuji Nakamoto^1
1Kyoto University Graduate School of Medicine, Kyoto, Japan

We evaluated magnetic susceptibility of the brain in 202 neonates and infants. We manually placed volumes of interest of the caudate nucleus, globus pallidus, putamen and ventral posterior lateral nucleus of the thalamus in the MNI space. Our study showed that elevation of magnetic susceptibility probably associated with iron deposition of the basal ganglia and thalamus increased with chronological age from birth to 2 years using volume-of-interest analysis.

Shiyu Yuan¹, Jingda Yang¹, Mengting Liu¹, Duan Xu², James Barkovich², and Hosung Kim^1
1USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, United States, ²Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States

The brain development of cyto- and myeloarchitecture undergoes rapid and intensive changes during the third trimester. Diffusion tensor imaging (DTI) probes the microstructural organization of brain tissue by measuring the three-dimensional spatial diffusion of water molecules1. Using mean diffusivity (MD) and fractional anisotropy (FA), we show the spatiotemporal pattern of cortical and superficial white matter maturation in preterm neonates. This result might be useful in the prediction of neurodevelopmental outcome and functional impairments in preterm survivors.

Sila Genc¹, Maxime Chamberland¹, Gareth Ball², Erika Raven¹, Isobel Ward¹, Chantal Tax¹, Marco Palombo³, and Derek Jones^1
1Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, United Kingdom, ²Developmental Imaging, Murdoch Children's Research Institute, Parkville, Australia, ³Centre for Medical Image Computing and Department of Computer Science, University College London, London, United Kingdom

MRI studies of cortical development have revealed macroscopic changes in morphology, with thickness/volume decreasing over childhood and adolescence. Recent microstructural modelling advances hold promise for quantifying the cellular changes driving these observations. We characterised cortical neurite and soma microstructure in 88 participants aged 8-18 years.

Key findings:

• a positive age-relationship for neurite fraction and orientation dispersion, suggesting that axons/processes increase in density and branch/elongate with age;
• a lower apparent soma radius with age, which may indicate selective neuronal soma loss and/or glial infiltration. 

Overall, our study provides in vivo evidence of distinct developmental patterns of cortical neurite and soma microstructure.

Xuan Bu^1,2, Yingxue Gao¹, Kaili Liang¹, Weijie Bao¹, Lu Lu¹, Ying Chen¹, Lanting Guo³, Qiyong Gong¹, Susumu Mori², and Xiaoqi Huang^1
1Radiology Department, Sichuan University, Chengdu, China, ²The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Psychiatry Department, Sichuan University, Chengdu, China

In current study, we discovered several multivariate patterns of white matter properties linked to clinical symptoms, cognition and behavior across children with and without ADHD. Each dimension of phenotype was linked to a specific pattern of white matter microstructure alterations. Furthermore, these associations captured deviations between children with and without ADHD and displayed developmental effects. Together, these results suggest that complex ADHD phenotypes are associated with specific patterns of abnormal white matter microstructure during brain development.

Georg Oeltzschner^1,2, Jason He³, Mark Mikkelsen^1,2, Alyssa DeRonda⁴, Deana Crocetti⁴, Stewart H. Mostofsky^4,5,6, Richard A.E. Edden^1,2, and Nicolaas A.J. Puts^3
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Department of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom, ⁴Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, United States, ⁵Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁶Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Abnormal perception of sensory input is among the core symptoms of autism spectrum disorders (ASD). Despite evidence for altered excitation-inhibition balance contributing to states of hyper- or hypo-excitability in ASD, findings have been mixed. In this study, we used magnetic resonance spectroscopy (MRS) in a large sample of children with ASD and typically developing children to measure levels of GABA and glutamate+glutamine (Glx). Elevated sensorimotor Glx levels in ASD correlated with vibrotactile frequency discrimination thresholds and caregiver-reported hyper- and hyporesponsivity to sensory stimuli, symptoms that are central to ASD. These results provide support for the excitation-inhibition imbalance theory of ASD.

Kathryn Y. Manning^1,2,3, Xiangyu Long^1,2,3, Lianne Tomfohr-Madsen^2,4,5, Gerald Giesbrecht^2,4,5,6, and Catherine Lebel^1,2,3
1Radiology, University of Calgary, Calgary, AB, Canada, ²Alberta Children's Hospital Research Institute, Calgary, AB, Canada, ³Hotchkiss Brain Institute, Calgary, AB, Canada, ⁴Psychology, University of Calgary, Calgary, AB, Canada, ⁵Pediatrics, University of Calgary, Calgary, AB, Canada, ⁶Community Health Sciences, Calgary, AB, Canada

We investigated the effects of prenatal maternal psychological distress in pregnant Canadian mothers during the COVID-19 pandemic on the early development of the infant brain. We scanned infants using the 3T MRI at the Alberta Children's hospital including resting state functional and diffusion MRI. We found that amygdala microstructural pathways were significantly related to functional connectivity between the right and left amygdala at 2-months of age. These infant MRI measures were correlated with maternal anxiety and psychological distress where we found relatively less mature tracts and lower amygdala-prefrontal functional connectivity were related to higher prenatal maternal psychological distress.   

Lara Bartels^1,2, Jonathan Doucette^1,2, Christoph Birkl^2,3,4, Yuting Zhang^5,6,7,8, Alexander Mark Weber^2,9, and Alexander Rauscher^1,2,9,10
1Department of Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, ²UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, ³Department of Neuroradiology, Medical University of Innsbruck, Innsbruck, Austria, ⁴Department of Neurology, Medical University of Graz, Graz, Austria, ⁵Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China, ⁶Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Chongqing, China, ⁷Key Laboratory of Pediatrics in Chongqing, Chongqing Medical University, Chongqing, China, ⁸Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China, ⁹Division of Neurology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada, ¹⁰Department of Radiology, University of British Columbia, Vancouver, BC, Canada

In adult White Matter (WM), tissue orientation effects on $$$R_2$$$ are best described by diffusion within field inhomogeneities created by the myelin sheath. Here we studied how $$$R_2$$$ relaxation depends on white matter fibre orientation in the human newborn brain in vivo. We found that the orientation dependency is very different from adults and best described by a model of dipole-dipole interaction.

Rahul Chandwani¹, Julia Kline¹, Karen Harpster^2,3,4, Jean Tkach^5,6,7, and Nehal Parikh^1,2
1Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States, ³Division of Occupational Therapy and Physical Therapy, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁴Department of Rehabilitation, Exercise and Nutrition Sciences, University of Cincinnati College of Allied Health Sciences, Cincinnati, OH, United States, ⁵Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁶Imaging Research Center, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁷Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States

Very preterm (VPT) infants are at high risk of motor impairments such as cerebral palsy (CP). Currently, qualitative findings from structural MRI and outcomes from clinical assessments are insufficient for early, accurate diagnosis of CP. In a multicenter cohort of 263 VPT infants, we derived macro and microstructural biomarkers of sensorimotor white matter tracts from term-equivalent age diffusion MRI. We observed consistent negative associations between these metrics – fiber density, fiber cross-section, and combined fiber density and cross-section – and early diagnosis of CP. These findings enhance our understanding of the pathophysiology of CP in VPT infants.    

Gemma Sullivan¹, Manuel Cabez¹, Kadi Vaher¹, Paola Galdi¹, Gill Black¹, David Q Stoye¹, Alan J Quigley², Elizabeth N York³, Michael J Thrippleton³, Mark E Bastin³, and James P Boardman^1,3
1MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom, ²Department of Paediatric Radiology, Royal Hospital for Sick Children, Edinburgh, Edinburgh, United Kingdom, ³Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom

Preterm birth is closely associated with altered white matter microstructure and dysconnectivity of developing neural networks with increased risk of long-term neurodevelopmental impairment. Nutritional exposures in the weeks after preterm birth affect head growth, brain macro- and micro- structure, and are associated with neurocognitive ability; the mechanisms underlying these associations are uncertain. By combining nutritional data with myelin-weighted imaging, we show that early breast milk exposure after preterm birth is associated with improved white matter myelination at term-equivalent age.

Sean Deoni¹, Lexie Volpe², Jennifer Beauchemin², and Viren D'Sa^3
1Bill & Melinda Gates Foundation, Seattle, WA, United States, ²Advanced Baby Imaging Lab, Rhode Island Hospital, Providence, RI, United States, ³Pediatrics, Rhode Island Hospital, Providence, RI, United States

Infancy and childhood are important developmental periods punctuated by rapid brain development and cognitive growth, however, direct and longitudinal analysis of the relationships between maturing brain structure and evolving cognitive skill in human infants is sparse. Here we used longitudinal and myelin-sensitive MRI measures from a large cohort of neurotypical children to examine patterns of myelination throughout the brain and link these patterns to concurrently evolving motor, visual, and language skills. Results revealed a core system of central brain regions that contributed broadly across cognitive domains as well as domain-specific regions that align with known functional specialization.

Melanie Morrison¹, Sivakami Avadappian¹, Angela Jakary¹, Erin Felton², Schuyler Stoller³, Sabine Mueller³, and Janine Lupo^1
1Radiology, UCSF, San Francisco, CA, United States, ²UCSF, San Francisco, CA, United States, ³Neurology, UCSF, San Francisco, CA, United States

This is a multimodal 7T MRI study evaluating imaging biomarkers of cognition in young brain tumor patients.