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Kratimenos P, Sanidas G, Simonti G, Byrd C, Gallo V. The shifting landscape of the preterm brain. Neuron 2025:S0896-6273(25)00224-7. [PMID: 40239653 DOI: 10.1016/j.neuron.2025.03.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/16/2025] [Accepted: 03/19/2025] [Indexed: 04/18/2025]
Abstract
Preterm birth remains a significant global health concern despite advancements in neonatal care. While survival rates have increased, the long-term neurodevelopmental consequences of preterm birth persist. Notably, the profile of the preterm infant has shifted, with infants at earlier gestational ages surviving and decreased rates of gross structural injury secondary to intracranial hemorrhage. However, these infants are still vulnerable to insults, including hypoxia-ischemia, inflammation, and disrupted in utero development, impinging on critical developmental processes, which can lead to neuronal and oligodendrocyte injury and impaired brain function. Consequently, preterm infants often experience a range of neurodevelopmental disorders, such as cognitive impairment and behavioral problems. Here, we address mechanisms underlying preterm brain injury and explore existing and new investigational therapeutic strategies. We discuss how gestational age influences brain development and how interventions, including pharmacological and non-pharmacological approaches, mitigate the effects of preterm birth complications and improve the long-term outcomes of preterm infants.
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Affiliation(s)
- Panagiotis Kratimenos
- Children's National Research Institute, Washington, DC, USA; George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Georgios Sanidas
- Children's National Research Institute, Washington, DC, USA; George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Gabriele Simonti
- Children's National Research Institute, Washington, DC, USA; George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Chad Byrd
- Children's National Research Institute, Washington, DC, USA; George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Vittorio Gallo
- Seattle Children's Research Institute, Seattle, WA, USA; The University of Washington School of Medicine, Seattle, WA, USA.
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2
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Hayakawa K, Tanda K, Nishimoto M, Nishimura A, Kinoshita D, Sano Y. Usefulness of apparent diffusion coefficient values for assessment of MRI abnormality at term equivalent age in low-birth-weight infants weighing less than 1500 g. Jpn J Radiol 2025; 43:502-508. [PMID: 39466355 DOI: 10.1007/s11604-024-01682-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 10/12/2024] [Indexed: 10/30/2024]
Abstract
OBJECTIVE To determine whether apparent diffusion coefficient (ADC) measurements at term equivalent age (TEA) are useful for assessment of major abnormalities revealed by MRI. MATERIALS AND METHODS Of 405 neonates who underwent MRI during the period 2016-2022, 101 low birth weight (LBW) infants (birth weight < 1500 g) were imaged at TEA. ADC values were measured in the thalamus, basal ganglia, anterior and posterior centrum semiovale, pons, and cerebellar hemisphere. The ADC values in LBW infants with and without major abnormalities evident on MRI were compared at the above six sites. Abnormal findings included IVH-3 IVH-4, more than six punctate white matter lesion, white matter injury (cystic or non-cystic), and major cerebellar hemorrhage. LBW infants overall (N = 101) and an extreme LBW (ELBW) group (< 1000 g) (N = 55) were compared and area under the curve was calculated using ROC analysis. RESULT There were no difference in ADC values between LBW infants with and without major abnormalities. In ELBW infants, ADC values in the cerebellum were higher when major abnormalities were present (p = 0.045). ROC analysis yielded AUC < 0.7 for both LBW cases overall and ELBW cases. CONCLUSION For LBW infants overall, ADC measurements alone at TEA are not very useful for differentiation between individuals with and without major abnormalities, but ELBW infants with major abnormalitiesshowed higher ADC values in the cerebellum, suggesting that the normal reduction of ADC occurring with maturation between preterm birth and TEA may be impaired.
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Affiliation(s)
- Katsumi Hayakawa
- Department of Diagnostic Radiology, Red Cross Kyoto Daiichi Hospital, 15-749 Hon-Machi, Higashiyama-Ku, Kyoto, 605-0981, Japan.
- Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
| | - Koichi Tanda
- Department of Neonatology, Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
- Department of Pediatrics, Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Masakazu Nishimoto
- Department of Diagnostic Radiology, Red Cross Kyoto Daiichi Hospital, 15-749 Hon-Machi, Higashiyama-Ku, Kyoto, 605-0981, Japan
- Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akira Nishimura
- Department of Neonatology, Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Daisuke Kinoshita
- Department of Neonatology, Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Yuko Sano
- Department of Diagnostic Radiology, Red Cross Kyoto Daiichi Hospital, 15-749 Hon-Machi, Higashiyama-Ku, Kyoto, 605-0981, Japan
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3
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Bahari F, Dzhala V, Balena T, Lillis KP, Staley KJ. Intraventricular haemorrhage in premature infants: the role of immature neuronal salt and water transport. Brain 2024; 147:3216-3233. [PMID: 38815055 PMCID: PMC11370806 DOI: 10.1093/brain/awae161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 04/25/2024] [Accepted: 04/28/2024] [Indexed: 06/01/2024] Open
Abstract
Intraventricular haemorrhage is a common complication of premature birth. Survivors are often left with cerebral palsy, intellectual disability and/or hydrocephalus. Animal models suggest that brain tissue shrinkage, with subsequent vascular stretch and tear, is an important step in the pathophysiology, but the cause of this shrinkage is unknown. Clinical risk factors for intraventricular haemorrhage are biomarkers of hypoxic-ischaemic stress, which causes mature neurons to swell. However, immature neuronal volume might shift in the opposite direction in these conditions. This is because immature neurons express the chloride, salt and water transporter NKCC1, which subserves regulatory volume increases in non-neural cells, whereas mature neurons express KCC2, which subserves regulatory volume decreases. When hypoxic-ischaemic conditions reduce active ion transport and increase the cytoplasmic membrane permeability, the effects of these transporters are diminished. Consequentially, mature neurons swell (cytotoxic oedema), whereas immature neurons might shrink. After hypoxic-ischaemic stress, in vivo and in vitro multi-photon imaging of perinatal transgenic mice demonstrated shrinkage of viable immature neurons, bulk tissue shrinkage and blood vessel displacement. Neuronal shrinkage was correlated with age-dependent membrane salt and water transporter expression using immunohistochemistry. Shrinkage of immature neurons was prevented by prior genetic or pharmacological inhibition of NKCC1 transport. These findings open new avenues of investigation for the detection of acute brain injury by neuroimaging, in addition to prevention of neuronal shrinkage and the ensuing intraventricular haemorrhage, in premature infants.
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Affiliation(s)
- Fatemeh Bahari
- Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
| | - Volodymyr Dzhala
- Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
| | - Trevor Balena
- Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
| | - Kyle P Lillis
- Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
| | - Kevin J Staley
- Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
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Zhang C, Zhu Z, Wang K, Moon BF, Zhang B, Shen Y, Wang Z, Zhao X, Zhang X. Assessment of brain structure and volume reveals neurodevelopmental abnormalities in preterm infants with low-grade intraventricular hemorrhage. Sci Rep 2024; 14:5709. [PMID: 38459090 PMCID: PMC10923809 DOI: 10.1038/s41598-024-56148-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 03/01/2024] [Indexed: 03/10/2024] Open
Abstract
There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks' corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P < 0.05). BPF, RK in the cerebellum, MK in the genu of the corpus callosum, and MK in the thalamus of preterm infants with low-grade IVH were associated with lower NBNA scores (r = 0.831, 0.836, 0.728, 0.772, P < 0.05). DKI and Synthetic MRI can quantitatively evaluate the microstructure alterations and brain volumes in preterm infants with low-grade IVH, which provides clinicians with a more comprehensive and accurate neurobehavioral assessment of preterm infants with low-grade IVH.
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Affiliation(s)
- Chunxiang Zhang
- Department of Radiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, China
| | | | - Kaiyu Wang
- GE Healthcare, MR Research China, Beijing, China
| | - Brianna F Moon
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Bohao Zhang
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, China
| | - Yanyong Shen
- Department of Radiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zihe Wang
- Zhengzhou University, Zhengzhou, China
| | - Xin Zhao
- Department of Radiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, China.
| | - Xiaoan Zhang
- Department of Radiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- Institute of Neuroscience, Zhengzhou University, Zhengzhou, China.
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Merisaari H, Karlsson L, Scheinin NM, Shulist SJ, Lewis JD, Karlsson H, Tuulari JJ. Effect of number of diffusion encoding directions in neonatal diffusion tensor imaging using Tract-Based Spatial Statistical analysis. Eur J Neurosci 2023; 58:3827-3837. [PMID: 37641861 DOI: 10.1111/ejn.16135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 08/09/2023] [Accepted: 08/12/2023] [Indexed: 08/31/2023]
Abstract
Diffusion tensor imaging (DTI) has been used to study the developing brain in early childhood, infants and in utero studies. In infants, number of used diffusion encoding directions has traditionally been smaller in earlier studies down to the minimum of 6 orthogonal directions. Whereas the more recent studies often involve more directions, number of used directions remain an issue when acquisition time is optimized without compromising on data quality and in retrospective studies. Variability in the number of used directions may introduce bias and uncertainties to the DTI scalar estimates that affect cross-sectional and longitudinal study of the brain. We analysed DTI images of 133 neonates, each data having 54 directions after quality control, to evaluate the effect of number of diffusion weighting directions from 6 to 54 with interval of 6 to the DTI scalars with Tract-Based Spatial Statistics (TBSS) analysis. The TBSS analysis was applied to DTI scalar maps, and the mean region of interest (ROI) values were extracted using JHU atlas. We found significant bias in ROI mean values when only 6 directions were used (positive in fractional anisotropy [FA] and negative in fractional anisotropy [MD], axial diffusivity [AD] and fractional anisotropy [RD]), while when using 24 directions and above, the difference to scalar values calculated from 54 direction DTI was negligible. In repeated measures voxel-wise analysis, notable differences to 54 direction DTI were observed with 6, 12 and 18 directions. DTI measurements from data with at least 24 directions may be used in comparisons with DTI measurements from data with higher numbers of directions.
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Affiliation(s)
- Harri Merisaari
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, Turku University Central Hospital and University of Turku, Turku, Finland
- Department of Radiology, Turku University Central Hospital and University of Turku, Turku, Finland
| | - Linnea Karlsson
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, Turku University Central Hospital and University of Turku, Turku, Finland
- Department of Paediatrics and Adolescent Medicine, Turku University Central Hospital and University of Turku, Turku, Finland
- Department of Psychiatry, Turku University Hospital and University of Turku, Turku, Finland
| | - Noora M Scheinin
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, Turku University Central Hospital and University of Turku, Turku, Finland
- Department of Psychiatry, Turku University Hospital and University of Turku, Turku, Finland
| | - Satu J Shulist
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, Turku University Central Hospital and University of Turku, Turku, Finland
| | - John D Lewis
- Montreal Neurological Institute, McGill University, Montreal, Québec, Canada
| | - Hasse Karlsson
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, Turku University Central Hospital and University of Turku, Turku, Finland
- Department of Psychiatry, Turku University Hospital and University of Turku, Turku, Finland
| | - Jetro J Tuulari
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, Turku University Central Hospital and University of Turku, Turku, Finland
- Turku Collegium of Science, Medicine and Technology, University of Turku, Turku, Finland
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Quinones JF, Hildebrandt A, Pavan T, Thiel CM, Heep A. Preterm birth and neonatal white matter microstructure in in-vivo reconstructed fiber tracts among audiovisual integration brain regions. Dev Cogn Neurosci 2023; 60:101202. [PMID: 36731359 PMCID: PMC9894786 DOI: 10.1016/j.dcn.2023.101202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 01/02/2023] [Accepted: 01/25/2023] [Indexed: 01/28/2023] Open
Abstract
Individuals born preterm are at risk of developing a variety of sequelae. Audiovisual integration (AVI) has received little attention despite its facilitating role in the development of socio-cognitive abilities. The present study assessed the association between prematurity and in-vivo reconstructed fiber bundles among brain regions relevant for AVI. We retrieved data from 63 preterm neonates enrolled in the Developing Human Connectome Project (http://www.developingconnectome.org/) and matched them with 63 term-born neonates from the same study by means of propensity score matching. We performed probabilistic tractography, DTI and NODDI analysis on the traced fibers. We found that specific DTI and NODDI metrics are significantly associated with prematurity in neonates matched for postmenstrual age at scan. We investigated the spatial overlap and developmental order of the reconstructed tractograms between preterm and full-term neonates. Permutation-based analysis revealed significant differences in dice similarity coefficients and developmental order between preterm and full term neonates at the group level. Contrarily, no group differences in the amount of interindividual variability of DTI and NODDI metrics were observed. We conclude that microstructural detriment in the reconstructed fiber bundles along with developmental and morphological differences are likely to contribute to disadvantages in AVI in preterm individuals.
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Affiliation(s)
- Juan F Quinones
- Psychological Methods and Statistics, Department of Psychology, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany; Cluster of Excellence Hearing4all, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.
| | - Andrea Hildebrandt
- Psychological Methods and Statistics, Department of Psychology, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany; Cluster of Excellence Hearing4all, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany; Research Center Neurosensory Science, Carl von Ossietzky Universität Oldenburg, Germany.
| | - Tommaso Pavan
- Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Christiane M Thiel
- Cluster of Excellence Hearing4all, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany; Research Center Neurosensory Science, Carl von Ossietzky Universität Oldenburg, Germany; Biological Psychology, Department of Psychology, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany
| | - Axel Heep
- Research Center Neurosensory Science, Carl von Ossietzky Universität Oldenburg, Germany; Klinik für Neonatologie, Intensivmedizin und Kinderkardiologie, Oldenburg, Germany
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7
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Petri S, Tinelli F. Visual impairment and periventricular leukomalacia in children: A systematic review. RESEARCH IN DEVELOPMENTAL DISABILITIES 2023; 135:104439. [PMID: 36796269 DOI: 10.1016/j.ridd.2023.104439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 11/16/2022] [Accepted: 01/18/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Thanks to Magnetic Resonance Imaging (MRI) it is now possible to diagnose lesions of the central nervous system (CNS) such as periventricular leukomalacia (PVL) from the first days of life. However, there are still few studies aimed at describing the relationship between MRI and the outcome of visual function in patients with PVL. AIM To systematically review and investigate the relationship between MRI neuroimaging and visual impairment arising from PVL. METHODS AND PROCEDURES Three electronic databases (PubMed, SCOPUS, Web of Science) were consulted from 15 June 2021-30 September 2021. Of the 81 records identified, 10 were selected for the systematic review. The STROBE Checklist was used to assess the quality of the observational studies. OUTCOME AND RESULTS PVL on MRI was found to have a strong association with visual impairment in the various aspects of visual function (visual acuity, ocular motility, visual field); in 60% of these articles, the selected subjects also reported damage to optical radiations. CONCLUSION AND IMPLICATIONS there is a clear need for more extensive and detailed studies on the correlation between PVL and visual impairment, in order to set up a personalized early therapeutic-rehabilitation plan. WHAT THIS PAPER ADDS?: Over the past decades numerous studies have reported increasing evidence that one of the most frequent sequelae in subjects with PVL, in addition to motor impairment, is the impairment of visual function even if it is still not clear what different authors mean with the term visual impairment. This systematic review presents an overview of the relationship between structural correlates of MRI and visual impairment in children with periventricular leukomalacia. Interesting correlations emerge between MRI radiological finding and consequences on visual function especially between damage to the periventricular white matter and the impairment of various aspects of visual function and also between the impairment of optical radiation and visual acuity. Thanks to this literature revision, it is now clear that MRI plays an important role in the screening and diagnosis of significant intracranial brain changes in very young children in particular about the outcome of visual function. This is of great relevance since that visual function represents one of the main adaptive functions in the development of the child.
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Affiliation(s)
- Stefania Petri
- Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy
| | - Francesca Tinelli
- Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy.
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Yuan S, Liu M, Kim S, Yang J, Barkovich AJ, Xu D, Kim H. Cyto/myeloarchitecture of cortical gray matter and superficial white matter in early neurodevelopment: multimodal MRI study in preterm neonates. Cereb Cortex 2022; 33:357-373. [PMID: 35235643 PMCID: PMC9837610 DOI: 10.1093/cercor/bhac071] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 01/21/2022] [Accepted: 01/22/2022] [Indexed: 01/19/2023] Open
Abstract
The cerebral cortex undergoes rapid microstructural changes throughout the third trimester. Recently, there has been growing interest on imaging features that represent cyto/myeloarchitecture underlying intracortical myelination, cortical gray matter (GM), and its adjacent superficial whitematter (sWM). Using 92 magnetic resonance imaging scans from 78 preterm neonates, the current study used combined T1-weighted/T2-weighted (T1w/T2w) intensity ratio and diffusion tensor imaging (DTI) measurements, including fractional anisotropy (FA) and mean diffusivity (MD), to characterize the developing cyto/myeloarchitectural architecture. DTI metrics showed a linear trajectory: FA decreased in GM but increased in sWM with time; and MD decreased in both GM and sWM. Conversely, T1w/T2w measurements showed a distinctive parabolic trajectory, revealing additional cyto/myeloarchitectural signature inferred. Furthermore, the spatiotemporal courses were regionally heterogeneous: central, ventral, and temporal regions of GM and sWM exhibited faster T1w/T2w changes; anterior sWM areas exhibited faster FA increases; and central and cingulate areas in GM and sWM exhibited faster MD decreases. These results may explain cyto/myeloarchitectural processes, including dendritic arborization, synaptogenesis, glial proliferation, and radial glial cell organization and apoptosis. Finally, T1w/T2w values were significantly associated with 1-year language and cognitive outcome scores, while MD significantly decreased with intraventricular hemorrhage.
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Affiliation(s)
- Shiyu Yuan
- Department of Neurology, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Mengting Liu
- Department of Neurology, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Sharon Kim
- Department of Neurology, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Jingda Yang
- Department of Neurology, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Anthony James Barkovich
- Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Duan Xu
- Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Hosung Kim
- Department of Neurology, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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9
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Chen R, Sun C, Liu T, Liao Y, Wang J, Sun Y, Zhang Y, Wang G, Wu D. Deciphering the developmental order and microstructural patterns of early white matter pathways in a diffusion MRI based fetal brain atlas. Neuroimage 2022; 264:119700. [PMID: 36270621 DOI: 10.1016/j.neuroimage.2022.119700] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 10/14/2022] [Accepted: 10/18/2022] [Indexed: 11/09/2022] Open
Abstract
White matter (WM) of the fetal brain undergoes rapid development to form early structural connections. Diffusion magnetic resonance imaging (dMRI) has shown to be a useful tool to depict fetal brain WM in utero, and many studies have observed increasing fractional anisotropy and decreasing diffusivity in the fetal brain during the second-to-third trimester, whereas others reported non-monotonic changes. Unbiased dMRI atlases of the fetal brain are important for characterizing the developmental trajectories of WM and providing normative references for in utero diagnosis of prenatal abnormalities. To date, the sole fetal brain dMRI atlas was collected from a Caucasian/mixed population and was constructed based on the diffusion tensor model with limited spatial resolution. In this work, we proposed a fiber orientation distribution (FOD) based pipeline for generating fetal brain dMRI atlases, which showed better registration accuracy than a diffusion tensor based pipeline. Based on the FOD-based pipeline, we constructed the first Chinese fetal brain dMRI atlas using 89 dMRI scans of normal fetuses at gestational age between 24 and 38 weeks. Complex non-monotonic trends of tensor- and FOD-derived microstructural parameters in eight WM tracts were observed, which jointly pointed to different phases of microstructural development. Specifically, we speculated that the turning point of the diffusivity trajectory may correspond to the starting point of pre-myelination, based on which, the developmental order of WM tracts can be mapped and the order was in agreement with the order of myelination from histological studies. The normative atlas also provided a reference for the detection of abnormal WM development, such as that in congenital heart disease. Therefore, the established high-order fetal brain dMRI atlas depicted the spatiotemporal pattern of early WM development, and findings may help decipher the distinct microstructural events in utero.
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Affiliation(s)
- Ruike Chen
- Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China
| | - Cong Sun
- Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Tingting Liu
- Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China
| | - Yuhao Liao
- Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China
| | | | - Yi Sun
- MR Collaboration, Siemens Healthineers Ltd., Shanghai, China
| | - Yi Zhang
- Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China
| | - Guangbin Wang
- Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
| | - Dan Wu
- Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
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Nieuwets A, Cizmeci MN, Groenendaal F, Leijser LM, Koopman C, Benders MJNL, Dudink J, de Vries LS, van der Aa NE. Post-hemorrhagic ventricular dilatation affects white matter maturation in extremely preterm infants. Pediatr Res 2022; 92:225-232. [PMID: 34446847 DOI: 10.1038/s41390-021-01704-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/20/2021] [Accepted: 08/08/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Data on microstructural white matter integrity in preterm infants with post-hemorrhagic ventricular dilatation (PHVD) using diffusion tensor imaging (DTI) are limited. Also, to date, no study has focused on the DTI changes in extremely preterm (EP) infants with PHVD. METHODS A case-control study of EP infants <28 weeks' gestation with PHVD was conducted. Diffusivity and fractional anisotropy (FA) values of corticospinal tracts (CST) and corpus callosum (CC) were measured using DTI at term-equivalent age. Outcomes were assessed at 2-years-corrected age. RESULTS Twenty-one infants with PHVD and 21 matched-controls were assessed. FA values in the CC were lower in infants with PHVD compared with controls (mean difference, 0.05 [95% confidence interval (CI), 0.02-0.08], p < 0.001). In infants with periventricular hemorrhagic infarction, FA values in the CC were lower than in controls (mean difference, 0.05 [95% CI, 0.02-0.09], p = 0.005). The composite cognitive and motor scores were associated with the FA value of the CC (coefficient 114, p = 0.01 and coefficient 147, p = 0.004; respectively). CONCLUSIONS Extremely preterm infants with PHVD showed lower FA values in CC. A positive correlation was also shown between the composite cognitive and motor scores and FA value of the CC at 2-years-corrected age. IMPACT Extremely preterm infants with post-hemorrhagic ventricular dilatation showed lower fractional anisotropy values in their corpus callosum compared with controls reflecting the impaired microstructure of these commissural nerve fibers that are adjacent to the dilated ventricles. Impaired microstructure of the corpus callosum was shown to be associated with cognitive and motor scores at 2-years-corrected age.
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Affiliation(s)
- Astrid Nieuwets
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Mehmet N Cizmeci
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.,Division of Neonatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Floris Groenendaal
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Lara M Leijser
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.,Section of Neonatology, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Corine Koopman
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Manon J N L Benders
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jeroen Dudink
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Linda S de Vries
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands.,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Niek E van der Aa
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands. .,Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
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11
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Fiber tracing and microstructural characterization among audiovisual integration brain regions in neonates compared with young adults. Neuroimage 2022; 254:119141. [PMID: 35342006 DOI: 10.1016/j.neuroimage.2022.119141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 02/23/2022] [Accepted: 03/21/2022] [Indexed: 11/23/2022] Open
Abstract
Audiovisual integration has been related with cognitive-processing and behavioral advantages, as well as with various socio-cognitive disorders. While some studies have identified brain regions instantiating this ability shortly after birth, little is known about the structural pathways connecting them. The goal of the present study was to reconstruct fiber tracts linking AVI regions in the newborn in-vivo brain and assess their adult-likeness by comparing them with analogous fiber tracts of young adults. We performed probabilistic tractography and compared connective probabilities between a sample of term-born neonates (N = 311; the Developing Human Connectome Project (dHCP, http://www.developingconnectome.org) and young adults (N = 311 The Human Connectome Project; https://www.humanconnectome.org/) by means of a classification algorithm. Furthermore, we computed Dice coefficients to assess between-group spatial similarity of the reconstructed fibers and used diffusion metrics to characterize neonates' AVI brain network in terms of microstructural properties, interhemispheric differences and the association with perinatal covariates and biological sex. Overall, our results indicate that the AVI fiber bundles were successfully reconstructed in a vast majority of neonates, similarly to adults. Connective probability distributional similarities and spatial overlaps of AVI fibers between the two groups differed across the reconstructed fibers. There was a rank-order correspondence of the fibers' connective strengths across the groups. Additionally, the study revealed patterns of diffusion metrics in line with early white matter developmental trajectories and a developmental advantage for females. Altogether, these findings deliver evidence of meaningful structural connections among AVI regions in the newborn in-vivo brain.
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12
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Abstract
White matter injury (WMI) represents a frequent form of parenchymal brain injury in preterm neonates. Several dimensions of WMI are recognized, with distinct neuropathologic features involving a combination of destructive and maturational anomalies. Hypoxia-ischemia is the main mechanism leading to WMI and adverse white matter development, which result from injury to the oligodendrocyte precursor cells. Inflammation might act as a potentiator for WMI. A combination of hypoxia-ischemia and inflammation is frequent in several neonatal comorbidities such as postnatal infections, NEC and bronchopulmonary dysplasia, all known contributors to WMI. White matter injury is an important predictor of adverse neurodevelopmental outcomes. When WMI is detected on neonatal brain imaging, a detailed characterization of the injury (pattern of injury, severity and location) may enhance the ability to predict outcomes. This clinically-oriented review will provide an overview of the pathophysiology and imaging diagnosis of the multiple dimensions of WMI, will explore the association between postnatal complications and WMI, and will provide guidance on the signification of white matter anomalies for motor and cognitive development.
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Affiliation(s)
- Mireille Guillot
- Department of Pediatrics (Neurology), University of Toronto and the Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Toronto M5G 1X8, Canada; Department of Pediatrics (Neonatology), Université Laval and Centre Hospitalier Universitaire de Québec, Québec, Canada
| | - Steven P Miller
- Department of Pediatrics (Neurology), University of Toronto and the Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Toronto M5G 1X8, Canada.
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13
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Gano D, McQuillen P. How does the convergence of prematurity and congenital heart disease impact the developing brain? Semin Perinatol 2021; 45:151472. [PMID: 34452752 DOI: 10.1016/j.semperi.2021.151472] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Prematurity and congenital heart disease (CHD) are individually associated with increased risk of brain injury and adverse neurodevelopmental outcomes. Delayed brain development in newborns with CHD has been documented to begin in utero and predisposes newborns with CHD to brain injury. Little is known about the combined risks when prematurity and CHD co-occur. The purpose of this review is to highlight the unique vulnerability of preterm newborns with CHD to brain dysmaturation and brain injury, and the urgent need for prospective research.
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Affiliation(s)
- Dawn Gano
- Department of Neurology, University of California, San Francisco, United States; Department of Pediatrics, University of California, San Francisco, United States.
| | - Patrick McQuillen
- Department of Pediatrics, University of California, San Francisco, United States
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14
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Hedderich DM, Menegaux A, Li H, Schmitz-Koep B, Stämpfli P, Bäuml JG, Berndt MT, Bäuerlein FJB, Grothe MJ, Dyrba M, Avram M, Boecker H, Daamen M, Zimmer C, Bartmann P, Wolke D, Sorg C. Aberrant Claustrum Microstructure in Humans after Premature Birth. Cereb Cortex 2021; 31:5549-5559. [PMID: 34171095 DOI: 10.1093/cercor/bhab178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 04/28/2021] [Accepted: 05/19/2021] [Indexed: 01/01/2023] Open
Abstract
Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.
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Affiliation(s)
- Dennis M Hedderich
- Department of Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
| | - Aurore Menegaux
- Department of Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
| | - Hongwei Li
- Department of Informatics, Technical University of Munich, 85748 Garching, Germany
| | - Benita Schmitz-Koep
- Department of Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
| | - Philipp Stämpfli
- MR-Center of the Psychiatric Hospital and the Department of Child and Adolescent Psychiatry, University of Zurich, 8032 Zurich, Switzerland
| | - Josef G Bäuml
- Department of Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
| | - Maria T Berndt
- Department of Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
| | - Felix J B Bäuerlein
- Max Planck Institute of Biochemistry, Department of Molecular Structural Biology, 82152 Martinsried, Germany
| | - Michel J Grothe
- German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, 18147 Rostock, Germany.,Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain
| | - Martin Dyrba
- German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, 18147 Rostock, Germany
| | - Mihai Avram
- Department of Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.,Department of Psychiatry, Psychosomatics and Psychotherapy, Schleswig Holstein University Hospital, University Lübeck, 23538 Lübeck, Germany
| | - Henning Boecker
- Functional Neuroimaging Group, Department of Diagnostic and Interventional Radiology, University Hospital Bonn, 53127 Bonn, Germany
| | - Marcel Daamen
- Functional Neuroimaging Group, Department of Diagnostic and Interventional Radiology, University Hospital Bonn, 53127 Bonn, Germany.,Department of Neonatology, University Hospital Bonn, 53127 Bonn, Germany
| | - Claus Zimmer
- Department of Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
| | - Peter Bartmann
- Department of Neonatology, University Hospital Bonn, 53127 Bonn, Germany
| | - Dieter Wolke
- Department of Psychology, University of Warwick, CV4 7AL, Coventry, UK.,Warwick Medical School, University of Warwick, CV4 7AL, Coventry, UK
| | - Christian Sorg
- Department of Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.,Department of Psychiatry, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany
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15
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Wisnowski JL, Wintermark P, Bonifacio SL, Smyser CD, Barkovich AJ, Edwards AD, de Vries LS, Inder TE, Chau V. Neuroimaging in the term newborn with neonatal encephalopathy. Semin Fetal Neonatal Med 2021; 26:101304. [PMID: 34736808 PMCID: PMC9135955 DOI: 10.1016/j.siny.2021.101304] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Neuroimaging is widely used to aid in the diagnosis and clinical management of neonates with neonatal encephalopathy (NE). Yet, despite widespread use clinically, there are few published guidelines on neuroimaging for neonates with NE. This review outlines the primary patterns of brain injury associated with hypoxic-ischemic injury in neonates with NE and their frequency, associated neuropathological features, and risk factors. In addition, it provides an overview of neuroimaging methods, including the most widely used scoring systems used to characterize brain injury in these neonates and their utility as predictive biomarkers. Last, recommendations for neuroimaging in neonates with NE are presented.
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Affiliation(s)
- Jessica L Wisnowski
- Departments of Radiology and Pediatrics (Neonatology), Children's Hospital Los Angeles, 4650 Sunset Blvd. MS #81, Los Angeles CA 90027, USA.
| | - Pia Wintermark
- Department of Pediatrics (Neonatology), McGill University/Montreal Children's Hospital, Division of Newborn Medicine, Research Institute of the McGill University Health Centre, 1001 boul. Décarie, Site Glen Block E, EM0.3244, Montréal, QC H4A 3J1, Canada.
| | - Sonia L Bonifacio
- Division of Neonatal and Developmental Medicine, Department of Pediatrics (Neonatology), Lucile Packard Children's Hospital, Stanford University School of Medicine, 750 Welch Road, Suite 315, Palo Alto, CA 94304, USA.
| | - Christopher D Smyser
- Departments of Neurology, Radiology, and Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St. Louis, MO 63110-1093, USA.
| | - A James Barkovich
- Department of Radiology, UCSF Benioff Children's Hospital, University of California San Francisco, 505 Parnassus Avenue, M-391, San Francisco, CA 94143-0628, USA.
| | - A David Edwards
- Evelina London Children's Hospital, Centre for Developing Brain, King's College London, Westminster Bridge Road, London, SE1 7EH, United Kingdom.
| | - Linda S de Vries
- Department of Neonatology, University Medical Center Utrecht, Utrecht University, Lundlaan 6, 3584 EA, Utrecht, the Netherlands.
| | - Terrie E Inder
- Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
| | - Vann Chau
- Department of Pediatrics (Neurology), The Hospital for Sick Children, University of Toronto, 555 University Avenue, Room 6513, Toronto, ON M5G 1X8, Canada.
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16
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Cayam-Rand D, Guo T, Synnes A, Chau V, Mabbott C, Benavente-Fernández I, Grunau RE, Miller SP. Interaction between Preterm White Matter Injury and Childhood Thalamic Growth. Ann Neurol 2021; 90:584-594. [PMID: 34436793 DOI: 10.1002/ana.26201] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 08/09/2021] [Accepted: 08/15/2021] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The purpose of this study was to determine how preterm white matter injury (WMI) and long-term thalamic growth interact to predict 8-year neurodevelopmental outcomes. METHODS A prospective cohort of 114 children born at 24 to 32 weeks' gestational age (GA) underwent structural and diffusion tensor magnetic resonance imaging early in life (median 32 weeks), at term-equivalent age and at 8 years. Manual segmentation of neonatal WMI was performed on T1-weighted images and thalamic volumes were obtained using the MAGeT brain segmentation pipeline. Cognitive, motor, and visual-motor outcomes were evaluated at 8 years of age. Multivariable regression was used to examine the relationship among neonatal WMI volume, school-age thalamic volume, and neurodevelopmental outcomes. RESULTS School-age thalamic volumes were predicted by neonatal thalamic growth rate, GA, sex, and neonatal WMI volume (p < 0.0001). After accounting for total cerebral volume, WMI volume remained associated with school-age thalamic volume (β = -0.31, p = 0.005). In thalamocortical tracts, fractional anisotropy (FA) at term-equivalent age interacted with early WMI volume to predict school-age thalamic volumes (all p < 0.02). School-age thalamic volumes and neonatal WMI interacted to predict full-scale IQ (p = 0.002) and adverse motor scores among those with significant WMI (p = 0.01). Visual-motor scores were predicted by thalamic volumes (p = 0.04). INTERPRETATION In very preterm-born children, neonatal thalamic growth and WMI volume predict school-age thalamic volumes. The emergence at term of an interaction between FA and WMI to impact school-age thalamic volume indicates dysmaturation as a mechanism of thalamic growth failure. Cognition is predicted by the interaction of WMI and thalamic growth, highlighting the need to consider multiple dimensions of brain injury in these children. ANN NEUROL 2021;90:584-594.
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Affiliation(s)
- Dalit Cayam-Rand
- Department of Paediatrics, Hospital for Sick Children & University of Toronto, Toronto, ON, Canada
| | - Ting Guo
- Department of Paediatrics, Hospital for Sick Children & University of Toronto, Toronto, ON, Canada
| | - Anne Synnes
- Department of Pediatrics, University of British Columbia and BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Vann Chau
- Department of Paediatrics, Hospital for Sick Children & University of Toronto, Toronto, ON, Canada
| | - Connor Mabbott
- Department of Paediatrics, Hospital for Sick Children & University of Toronto, Toronto, ON, Canada.,Department of Physiology, University of Toronto, Toronto, ON, Canada
| | - Isabel Benavente-Fernández
- Department of Paediatrics, Hospital for Sick Children & University of Toronto, Toronto, ON, Canada.,Department of Neonatology & Biomedical Research and Innovation Institute of Cadiz, University Hospital Puerta del Mar, Cadiz, Spain
| | - Ruth E Grunau
- Department of Pediatrics, University of British Columbia and BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Steven P Miller
- Department of Paediatrics, Hospital for Sick Children & University of Toronto, Toronto, ON, Canada
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17
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Leijser LM, Scott JN, Roychoudhury S, Zein H, Murthy P, Thomas SP, Mohammad K. Post-hemorrhagic ventricular dilatation: inter-observer reliability of ventricular size measurements in extremely preterm infants. Pediatr Res 2021; 90:403-410. [PMID: 33184496 DOI: 10.1038/s41390-020-01245-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 10/09/2020] [Accepted: 10/16/2020] [Indexed: 11/09/2022]
Abstract
BACKGROUND Post-hemorrhagic ventricular dilatation (PHVD) in preterm infants can be assessed with ventricular size indices from cranial ultrasound. We explored inter-observer reliability of these indices for prediction of severe PHVD. METHODS For all 139 infants with IVH, serial neonatal ultrasound at 3 time points (days 4-7, day 14, 36 weeks PMA) were assessed independently by 3 observers with differing levels of training/experience. Ventricular index (VI), anterior horn width (AHW), and fronto-temporal horn ratio (FTHR) were measured and used to diagnose PHVD. For all, inter-observer reliability and predictive values for receipt of surgical intervention were calculated. RESULTS Inter-observer reliability for all observers varied from poor to excellent, with higher reliability for VI/AHW (ICC 0.49-0.84/0.51-0.81) than FTHR (0.41-0.82), particularly from the second week. Good-excellent inter-expertise reliability was found between observers with ample experience/training (0.65-0.99), particularly for VI and AHW, while poor-moderate when comparing with an inexperienced observer (0.28-0.88). Slightly higher predictive value for PHVD intervention (n = 12) was found for AHW (AUC 0.86-0.96) than for VI and FTHR (0.80-0.96/0.80-0.95). CONCLUSIONS AHW and VI are highly reproducible in experienced hands compared to FTHR, with AHW from the second week onwards being the strongest predictor for receiving surgical intervention for severe PHVD. AHW may aid in early PHVD diagnosis and decision-making on intervention. IMPACT While ventricular size indices from serial cUS are superior to clinical signs of increased intracranial pressure to assess PHVD, questions remained on their inter-observer reproducibility and reliability to predict severity of PHVD. AHW and VI are highly reproducible when performed by experienced clinicians. AHW from the second week of birth is the strongest predictor of PHVD onset and severity. AHW, combined with VI, may aid in early PHVD diagnosis and decision-making on need for surgical intervention. Consistent use of these indices has the potential to improve PHVD management and therewith the long-term outcomes in preterm infants.
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Affiliation(s)
- Lara M Leijser
- Section of Neonatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
| | - James N Scott
- Department of Diagnostic Imaging, University of Calgary, Calgary, AB, Canada
| | - Smita Roychoudhury
- Department of Pediatrics, McMaster Children's Hospital, Hamilton Health Sciences, Hamilton, ON, Canada
| | - Hussein Zein
- Section of Neonatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
| | - Prashanth Murthy
- Section of Neonatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
| | - Sumesh P Thomas
- Section of Neonatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
| | - Khorshid Mohammad
- Section of Neonatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
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18
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Kushwah S, Kumar A, Verma A, Basu S, Kumar A. Comparison of fractional anisotropy and apparent diffusion coefficient among hypoxic ischemic encephalopathy stages 1, 2, and 3 and with nonasphyxiated newborns in 18 areas of brain. Indian J Radiol Imaging 2021; 27:447-456. [PMID: 29379241 PMCID: PMC5761173 DOI: 10.4103/ijri.ijri_384_16] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Purpose To determine the area and extent of injury in hypoxic encephalopathy stages by diffusion tensor imaging (DTI) using parameters apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values and their comparison with controls without any evidence of asphyxia. To correlate the outcome of hypoxia severity clinically and significant changes on DTI parameter. Materials and Methods DTI was done in 50 cases at median age of 12 and 20 controls at median age of 7 days. FA and apparent diffusion coefficient (ADC) were measured in several regions of interest (ROI). Continuous variables were analyzed using Student's t-test. Categorical variables were compared by Fisher's exact test. Comparison among multiple groups was done using analysis of variance (ANOVA) and post hoc Bonferroni test. Results Abnormalities were more easily and accurately determined in ROI with the help of FA and ADC values. When compared with controls FA values were significantly decreased and ADC values were significantly increased in cases, in ROI including both right and left side of thalamus, basal ganglia, posterior limb of internal capsule, cerebral peduncle, corticospinal tracts, frontal, parietal, temporal, occipital with P value < 0.05. The extent of injury was maximum in stage-III. There was no significant difference among males and females. Conclusion Compared to conventional magnetic resonance imaging (MRI), the evaluation of FA and ADC values using DTI can determine the extent and severity of injury in hypoxic encephalopathy. It can be used for early determination of brain injury in these patients.
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Affiliation(s)
- Supriya Kushwah
- Department of Paediatrics, Yenepoya Medical College, Mangalore, Karnataka, India
| | - Ashok Kumar
- Department of Paediatrics, Institute of Medical Sciences, Varanasi, Uttar Pradesh, India
| | - Ashish Verma
- Department of Paediatrics, Institute of Medical Sciences, Varanasi, Uttar Pradesh, India
| | - Sriparna Basu
- Department of Paediatrics, Institute of Medical Sciences, Varanasi, Uttar Pradesh, India
| | - Ashutosh Kumar
- Department of Anaesthesia, KMC, Mangalore, Karnataka, India
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19
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Development of human white matter pathways in utero over the second and third trimester. Proc Natl Acad Sci U S A 2021; 118:2023598118. [PMID: 33972435 PMCID: PMC8157930 DOI: 10.1073/pnas.2023598118] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
During the second and third trimesters of human gestation, rapid neurodevelopment is underpinned by fundamental processes including neuronal migration, cellular organization, cortical layering, and myelination. In this time, white matter growth and maturation lay the foundation for an efficient network of structural connections. Detailed knowledge about this developmental trajectory in the healthy human fetal brain is limited, in part, due to the inherent challenges of acquiring high-quality MRI data from this population. Here, we use state-of-the-art high-resolution multishell motion-corrected diffusion-weighted MRI (dMRI), collected as part of the developing Human Connectome Project (dHCP), to characterize the in utero maturation of white matter microstructure in 113 fetuses aged 22 to 37 wk gestation. We define five major white matter bundles and characterize their microstructural features using both traditional diffusion tensor and multishell multitissue models. We found unique maturational trends in thalamocortical fibers compared with association tracts and identified different maturational trends within specific sections of the corpus callosum. While linear maturational increases in fractional anisotropy were seen in the splenium of the corpus callosum, complex nonlinear trends were seen in the majority of other white matter tracts, with an initial decrease in fractional anisotropy in early gestation followed by a later increase. The latter is of particular interest as it differs markedly from the trends previously described in ex utero preterm infants, suggesting that this normative fetal data can provide significant insights into the abnormalities in connectivity which underlie the neurodevelopmental impairments associated with preterm birth.
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20
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Structural Changes in the Cortico-Ponto-Cerebellar Axis at Birth are Associated with Abnormal Neurological Outcomes in Childhood. Clin Neuroradiol 2021; 31:1005-1020. [PMID: 33944956 DOI: 10.1007/s00062-021-01017-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 04/04/2021] [Indexed: 10/21/2022]
Abstract
White matter lesions in hypoxic-ischemic encephalopathy (HIE) are considered to be the important substrate of frequent neurological consequences in preterm infants. The aim of the study was to analyze volumes and tractographic parameters of the cortico-ponto-cerebellar axis to assess alterations in the periventricular fiber system and crossroads, corticopontine and corticospinal pathways and prospective transsynaptic changes of the cerebellum.Term infants (control), premature infants without (normotypic) and with perinatal HIE (HIE) underwent brain magnetic resonance imaging at term-equivalent age (TEA) and at 2 years. Cerebrum, cerebellum, brainstem divisions and ventrodorsal compartments volumetric analysis were performed, as well as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of corticopontine, corticospinal pathways and middle cerebellar peduncles. Amiel-Tison scale at TEA and the Hempel test at 2 years were assessed.Cerebellum, brainstem and its compartments volumes were decreased in normotypic and HIE groups at TEA, while at 2 years volumes were significantly reduced in the HIE group, accompanied by decreased volume and FA and increased ADC of corticopontine and corticospinal pathways. Negative association of the brainstem, cerebellum, mesencephalon, pons, corticopontine volumes and corticospinal pathway FA at TEA with the neurological score at 2 years. Cerebellum and pons volumes presented as potential prognostic indicators of neurological outcomes.Our findings agree that these pathways, as a part of the periventricular fiber system and crossroads, exhibit lesion-induced reaction and vulnerability in HIE. Structural differences between normotypic and HIE group at the 2 years suggest a different developmental structural plasticity.
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Quinones Sanchez JF, Liu X, Zhou C, Hildebrandt A. Nature and nurture shape structural connectivity in the face processing brain network. Neuroimage 2021; 229:117736. [PMID: 33486123 DOI: 10.1016/j.neuroimage.2021.117736] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 12/23/2020] [Accepted: 01/05/2021] [Indexed: 01/12/2023] Open
Abstract
Face processing is a key ability facilitating social cognition. Only a few studies explored how nature and nurture shape face processing ontogeny at the behavioral and neural level. Also, very little is known about the contributions of nature and nurture to the establishment of white matter fibers supporting this specific human ability. The main purpose of this study was to assess genetic and environmental influences on white matter bundles connecting atlas-defined and functionally-defined face-responsive areas in the brain. Diffusion weighted images from 408 twins (monozygotic = 264, dizygotic = 144) were obtained from the WU-Minn Human Connectome Project. Fractional anisotropy - a widely used measure of fiber quality - of seven white matter tracts in the face network and ten global white matter tracts was analyzed by means of Structural Equation Modeling for twin data. Results revealed small and moderate genetic effects on face network fiber quality in addition to their shared variance with global brain white matter integrity. Furthermore, a theoretically expected common latent factor accounted for limited genetic and larger environmental variance in multiple face network fibers. The findings suggest that both genetic and environmental factors explain individual differences in fiber quality within the face network, as compared with much larger genetic effects on global brain white matter quality. In addition to heritability, individual-specific environmental influences on the face processing brain network are large, a finding that suggests to connect nature and nurture views on this remarkably specific human ability.
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Affiliation(s)
| | - Xinyang Liu
- Department of Psychology, Carl von Ossietzky Universität Oldenburg, Germany; Department of Physics, Centre for Nonlinear Studies and Beijing-Hong Kong-Singapore Joint Centre for Nonlinear and Complex Systems (Hong Kong), Institute of Computational and Theoretical Studies, Hong Kong Baptist University, Hong Kong
| | - Changsong Zhou
- Department of Physics, Centre for Nonlinear Studies and Beijing-Hong Kong-Singapore Joint Centre for Nonlinear and Complex Systems (Hong Kong), Institute of Computational and Theoretical Studies, Hong Kong Baptist University, Hong Kong; Department of Physics, Zhejiang University, Hangzhou, China
| | - Andrea Hildebrandt
- Department of Psychology, Carl von Ossietzky Universität Oldenburg, Germany; Research Center Neurosensory Science, Carl von Ossietzky Universität Oldenburg, Germany.
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Mechanical Ventilation Duration, Brainstem Development, and Neurodevelopment in Children Born Preterm: A Prospective Cohort Study. J Pediatr 2020; 226:87-95.e3. [PMID: 32454115 DOI: 10.1016/j.jpeds.2020.05.039] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/22/2020] [Accepted: 05/18/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To determine, in children born preterm, the association of mechanical ventilation duration with brainstem development, white matter maturation, and neurodevelopmental outcomes at preschool age. STUDY DESIGN This prospective cohort study included 144 neonates born at <30 weeks of gestation (75 male, mean gestational age 27.1 weeks, SD 1.6) with regional brainstem volumes automatically segmented on magnetic resonance imaging at term-equivalent age (TEA). The white matter maturation was assessed by diffusion tensor imaging and tract-based spatial statistics. Neurodevelopmental outcomes were assessed at 4.5 years of age using the Movement Assessment Battery for Children, 2nd Edition, and the Wechsler Primary and Preschool Scale of Intelligence, 4th Edition, full-scale IQ. The association between the duration of mechanical ventilation and brainstem development was validated in an independent cohort of children born very preterm. RESULTS Each additional day of mechanical ventilation predicted lower motor scores (0.5-point decrease in the Movement Assessment Battery for Children, 2nd Edition, score by day of mechanical ventilation, 95% CI -0.6 to -0.3, P < .0001). Prolonged exposure to mechanical ventilation was associated with smaller pons and medulla volumes at TEA in 2 independent cohorts, along with widespread abnormalities in white matter maturation. Pons and medulla volumes at TEA predicted motor outcomes at 4.5 years of age. CONCLUSIONS In neonates born very preterm, prolonged mechanical ventilation is associated with impaired brainstem development, abnormal white matter maturation, and lower motor scores at preschool age. Further research is needed to better understand the neural pathological mechanisms involved.
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Azizollahi H, Aarabi A, Wallois F. Effect of structural complexities in head modeling on the accuracy of EEG source localization in neonates. J Neural Eng 2020; 17:056004. [PMID: 32942266 DOI: 10.1088/1741-2552/abb994] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Neonatal electroencephalography (EEG) source localization is highly prone to errors due to head modeling deficiencies. In this study, we investigated the effect of head model complexities on the accuracy of EEG source localization in full term neonates using a realistic volume conductor head model. APPROACH We performed numerical simulations to investigate source localization errors caused by cerebrospinal fluid (CSF) and fontanel exclusion and gray matter (GM)/white matter (WM) distinction using the finite element method. MAIN RESULTS Our results showed that the exclusion of CSF from the head model could cause significant localization errors mostly for sources closer to the inner surface of the skull. With a less pronounced effect compared to the CSF exclusion, the discrimination between GM and WM also widely affected all sources, especially those located in deeper structures. The exclusion of the fontanels from the head model led to source localization errors for sources located in areas beneath the fontanels. Our finding clearly shows that the CSF inclusion and GM/WM distinction in EEG inverse modeling can substantially reduce EEG source localization errors. Moreover, fontanels should be included in neonatal head models, particularly in source localization applications, in which sources of interest are located beneath or in vicinity of fontanels. SIGNIFICANCE Our findings have practical implications for a better understanding of the impact of head model complexities on the accuracy of EEG source localization in neonates.
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Affiliation(s)
- Hamed Azizollahi
- GRAMFC, Inserm U1105, University Research Center (CURS), CHU AMIENS - SITE SUD, Amiens, France
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Early application of caffeine improves white matter development in very preterm infants. Respir Physiol Neurobiol 2020; 281:103495. [DOI: 10.1016/j.resp.2020.103495] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 06/22/2020] [Accepted: 07/12/2020] [Indexed: 12/31/2022]
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Varişoğlu Y, Güngör Satilmiş I. The Effects of Listening to Music on Breast Milk Production by Mothers of Premature Newborns in the Neonatal Intensive Care Unit: A Randomized Controlled Study. Breastfeed Med 2020; 15:465-470. [PMID: 32423235 DOI: 10.1089/bfm.2020.0027] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Objective: This study was a randomized controlled experiment to determine the effects of listening to music on breast milk production in Turkish mothers with premature newborns. Methods: The study consisted of two groups of randomly selected mothers (n = 20 each) of newborns in the neonatal intensive care unit (NICU) of two university hospitals in Istanbul between November 2017 and November 2018. On the first day, all mothers were provided with training for milking with pumps. On the second through fourth days, mothers in the music group (MG) underwent two sessions of milking with music and a pump for 15 minutes at 11:00 and 16:00; the mothers in the control group underwent two sessions of milking without music. To evaluate stress levels, Spielberger's State-Trait Anxiety Inventory was administered and salivary cortisol tests were taken on the first and final days of the study. Results: The mean age of participants was 28.5 ± 5.3 years, the mean gestational week was 32.21 ± 2.26, and the mean birth weight of the newborns was 1748 ± 533.4 g. The state and total anxiety scores of the MG were statistically low (p < 0.05). There was no difference between the MG and control group in the amount of breast milk produced; however, the final test cortisol levels of the MG group were significantly lower compared with the pretest measurements (p < 0.05). Conclusion: Listening to music in the NICU while breastfeeding can help reduce stress levels in mothers to premature newborns and support breast milk production.
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Affiliation(s)
- Yeliz Varişoğlu
- Depertmant of Nursing, Faculty of Health Science, Istanbul Medipol University, Istanbul, Turkey
| | - Ilkay Güngör Satilmiş
- İlkay Güngör Satilmiş's Institution, Florence Nightingale Faculty of Nursing, Istanbul University Cerrahpasa, Istanbul, Turkey
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Wallois F, Routier L, Bourel-Ponchel E. Impact of prematurity on neurodevelopment. HANDBOOK OF CLINICAL NEUROLOGY 2020; 173:341-375. [PMID: 32958184 DOI: 10.1016/b978-0-444-64150-2.00026-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
The consequences of prematurity on brain functional development are numerous and diverse, and impact all brain functions at different levels. Prematurity occurs between 22 and 36 weeks of gestation. This period is marked by extreme dynamics in the physiologic maturation, structural, and functional processes. These different processes appear sequentially or simultaneously. They are dependent on genetic and/or environmental factors. Disturbance of these processes or of the fine-tuning between them, when caring for premature children, is likely to induce disturbances in the structural and functional development of the immature neural networks. These will appear as impairments in learning skills progress and are likely to have a lasting impact on the development of children born prematurely. The level of severity depends on the initial alteration, whether structural or functional. In this chapter, after having briefly reviewed the neurodevelopmental, structural, and functional processes, we describe, in a nonexhaustive manner, the impact of prematurity on the different brain, motor, sensory, and cognitive functions.
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Affiliation(s)
- Fabrice Wallois
- Research Group on Multimodal Analysis of Brain Function, Jules Verne Picardie University, Amiens, France; Department of Pediatric Functional Exploration of the Nervous System, University Hospital, Picardie, Amiens, France.
| | - Laura Routier
- Research Group on Multimodal Analysis of Brain Function, Jules Verne Picardie University, Amiens, France; Department of Pediatric Functional Exploration of the Nervous System, University Hospital, Picardie, Amiens, France
| | - Emilie Bourel-Ponchel
- Research Group on Multimodal Analysis of Brain Function, Jules Verne Picardie University, Amiens, France; Department of Pediatric Functional Exploration of the Nervous System, University Hospital, Picardie, Amiens, France
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Hou W, Tang PH, Agarwal P. The most useful cranial ultrasound predictor of neurodevelopmental outcome at 2 years for preterm infants. Clin Radiol 2019; 75:278-286. [PMID: 31870490 DOI: 10.1016/j.crad.2019.11.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Accepted: 11/20/2019] [Indexed: 12/01/2022]
Abstract
AIM To determine the most important cranial ultrasound predictors of abnormality associated with neurodevelopmental outcome at 2 years of age in preterm infants. MATERIALS AND METHODS A total of 343 preterm infants born between 2005 and 2010 and cared for in KK Women's and Children's Hospital, a tertiary paediatric hospital, with birth weight ≤1,250 g were assessed in this retrospective study. Serial cranial ultrasound examinations were examined for intraventricular haemorrhage and cystic periventricular leukomalacia. Ventricular-brain ratio on term equivalent cranial ultrasound was measured. Neurodevelopmental outcome was assessed by the performance on Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at 2 years corrected age. Mental delay was defined as having a combined Bayley-III score (the average of cognitive and language scores) <80. RESULTS The mean cognitive, language, and motor scores on Bayley-III in this cohort were 93±15, 83±18, and 92±15, respectively. Twenty-six percent of the preterm infants had mental delay and 4% had cerebral palsy. Ventricular-brain ratio >0.35 was the most significant factor associated with mental delay (odds ratio 5.28, 95% CI: 1.49-18.71, p=0.01). Other significant risk factors for mental delay were male gender, postnatal steroids, and necrotising enterocolitis, whereas maternal tertiary education was a protective factor against adverse outcome. CONCLUSION Ventricular-brain ratio >0.35 on term-equivalent cranial ultrasound in preterm infants is the strongest predictor for mental delay on Bayley score at 2 years of age.
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Affiliation(s)
- W Hou
- Duke NUS Medical School, 8 College Road, 169857, Singapore
| | - P H Tang
- Department of Diagnostic & Interventional Imaging, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore.
| | - P Agarwal
- Department of Neonatology, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore
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Boardman JP, Counsell SJ. Invited Review: Factors associated with atypical brain development in preterm infants: insights from magnetic resonance imaging. Neuropathol Appl Neurobiol 2019; 46:413-421. [PMID: 31747472 PMCID: PMC7496638 DOI: 10.1111/nan.12589] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 11/13/2019] [Indexed: 12/18/2022]
Abstract
Preterm birth (PTB) is a leading cause of neurodevelopmental and neurocognitive impairment in childhood and is closely associated with psychiatric disease. The biological and environmental factors that confer risk and resilience for healthy brain development and long‐term outcome after PTB are uncertain, which presents challenges for risk stratification and for the discovery and evaluation of neuroprotective strategies. Neonatal magnetic resonance imaging reveals a signature of PTB that includes dysconnectivity of neural networks and atypical development of cortical and deep grey matter structures. Here we provide a brief review of perinatal factors that are associated with the MRI signature of PTB. We consider maternal and foetal factors including chorioamnionitis, foetal growth restriction, socioeconomic deprivation and prenatal alcohol, drug and stress exposures; and neonatal factors including co‐morbidities of PTB, nutrition, pain and medication during neonatal intensive care and variation conferred by the genome/epigenome. Association studies offer the first insights into pathways to adversity and resilience after PTB. Future challenges are to analyse quantitative brain MRI data with collateral biological and environmental data in study designs that support causal inference, and ultimately to use the output of such analyses to stratify infants for clinical trials of therapies designed to improve outcome.
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Affiliation(s)
- J P Boardman
- MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK
| | - S J Counsell
- Centre for the Developing Brain, School of Imaging Sciences and Biomedical Engineering, King's College London, London, UK
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Yassin W, Kojima M, Owada K, Kuwabara H, Gonoi W, Aoki Y, Takao H, Natsubori T, Iwashiro N, Kasai K, Kano Y, Abe O, Yamasue H. Paternal age contribution to brain white matter aberrations in autism spectrum disorder. Psychiatry Clin Neurosci 2019; 73:649-659. [PMID: 31271249 DOI: 10.1111/pcn.12909] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 05/29/2019] [Accepted: 07/01/2019] [Indexed: 12/16/2022]
Abstract
AIM Although advanced parental age holds an increased risk for autism spectrum disorder (ASD), its role as a potential risk factor for an atypical white matter development underlying the pathophysiology of ASD has not yet been investigated. The current study was aimed to detect white matter disparities in ASD, and further investigate the relationship of paternal and maternal age at birth with such disparities. METHODS Thirty-nine adult males with high-functioning ASD and 37 typically developing (TD) males were analyzed in the study. The FMRIB Software Library and tract-based spatial statistics were utilized to process and analyze the diffusion tensor imaging data. RESULTS Subjects with ASD exhibited significantly higher mean diffusivity (MD) and radial diffusivity (RD) in white matter fibers, including the association (inferior fronto-occipital fasciculus, right inferior longitudinal fasciculus, superior longitudinal fasciculi, uncinate fasciculus, and cingulum), commissural (forceps minor), and projection tracts (anterior thalamic radiation and right corticospinal tract) compared to TD subjects (Padjusted < 0.05). No differences were seen in either fractional anisotropy or axial diffusivity. Linear regression analyses assessing the relationship between parental ages and the white matter aberrations revealed a positive correlation between paternal age (PA), but not maternal age, and both MD and RD in the affected fibers (Padjusted < 0.05). Multiple regression showed that only PA was a predictor of both MD and RD. CONCLUSION Our findings suggest that PA contributes to the white matter disparities seen in individuals with ASD compared to TD subjects.
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Affiliation(s)
- Walid Yassin
- Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masaki Kojima
- Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keiho Owada
- Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hitoshi Kuwabara
- Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Wataru Gonoi
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuta Aoki
- Department of Neuropsychiatry, School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidemasa Takao
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsunobu Natsubori
- Department of Neuropsychiatry, School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norichika Iwashiro
- Department of Neuropsychiatry, School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoto Kasai
- Department of Neuropsychiatry, School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yukiko Kano
- Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Abe
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidenori Yamasue
- Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Zöllei L, Jaimes C, Saliba E, Grant PE, Yendiki A. TRActs constrained by UnderLying INfant anatomy (TRACULInA): An automated probabilistic tractography tool with anatomical priors for use in the newborn brain. Neuroimage 2019; 199:1-17. [PMID: 31132451 PMCID: PMC6688923 DOI: 10.1016/j.neuroimage.2019.05.051] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 05/14/2019] [Accepted: 05/18/2019] [Indexed: 10/26/2022] Open
Abstract
The ongoing myelination of white-matter fiber bundles plays a significant role in brain development. However, reliable and consistent identification of these bundles from infant brain MRIs is often challenging due to inherently low diffusion anisotropy, as well as motion and other artifacts. In this paper we introduce a new tool for automated probabilistic tractography specifically designed for newborn infants. Our tool incorporates prior information about the anatomical neighborhood of white-matter pathways from a training data set. In our experiments, we evaluate this tool on data from both full-term and prematurely born infants and demonstrate that it can reconstruct known white-matter tracts in both groups robustly, even in the presence of differences between the training set and study subjects. Additionally, we evaluate it on a publicly available large data set of healthy term infants (UNC Early Brain Development Program). This paves the way for performing a host of sophisticated analyses in newborns that we have previously implemented for the adult brain, such as pointwise analysis along tracts and longitudinal analysis, in both health and disease.
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Affiliation(s)
- Lilla Zöllei
- Massachusetts General Hospital, Boston, United States.
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Córcoles-Parada M, Giménez-Mateo R, Serrano-Del-Pueblo V, López L, Pérez-Hernández E, Mansilla F, Martínez A, Onsurbe I, San Roman P, Ubero-Martinez M, Clayden JD, Clark CA, Muñoz-López M. Born Too Early and Too Small: Higher Order Cognitive Function and Brain at Risk at Ages 8-16. Front Psychol 2019; 10:1942. [PMID: 31551853 PMCID: PMC6743534 DOI: 10.3389/fpsyg.2019.01942] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 08/07/2019] [Indexed: 11/13/2022] Open
Abstract
Prematurity presents a risk for higher order cognitive functions. Some of these deficits manifest later in development, when these functions are expected to mature. However, the causes and consequences of prematurity are still unclear. We conducted a longitudinal study to first identify clinical predictors of ultrasound brain abnormalities in 196 children born very preterm (VP; gestational age ≤32 weeks) and with very low birth weight (VLBW; birth weight ≤1500 g). At ages 8-16, the subset of VP-VLBW children without neurological findings (124) were invited for a neuropsychological assessment and an MRI scan (41 accepted). Of these, 29 met a rigorous criterion for MRI quality and an age, and gender-matched control group (n = 14) was included in this study. The key findings in the VP-VLBW neonates were: (a) 37% of the VP-VLBW neonates had ultrasound brain abnormalities; (b) gestational age and birth weight collectively with hospital course (i.e., days in hospital, neonatal intensive care, mechanical ventilation and with oxygen therapy, surgeries, and retinopathy of prematurity) predicted ultrasound brain abnormalities. At ages 8-16, VP-VLBW children showed: a) lower intelligent quotient (IQ) and executive function; b) decreased gray and white matter (WM) integrity; (c) IQ correlated negatively with cortical thickness in higher order processing cortical areas. In conclusion, our data indicate that facets of executive function and IQ are the most affected in VP-VLBW children likely due to altered higher order cortical areas and underlying WM.
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Affiliation(s)
- Marta Córcoles-Parada
- Human Neuroanatomy Laboratory, School of Medicine and Regional Centre for Biomedical Research, University of Castilla-La Mancha, Albacete, Spain
| | - Rocio Giménez-Mateo
- Human Neuroanatomy Laboratory, School of Medicine and Regional Centre for Biomedical Research, University of Castilla-La Mancha, Albacete, Spain
| | - Victor Serrano-Del-Pueblo
- Human Neuroanatomy Laboratory, School of Medicine and Regional Centre for Biomedical Research, University of Castilla-La Mancha, Albacete, Spain
| | - Leidy López
- Human Neuroanatomy Laboratory, School of Medicine and Regional Centre for Biomedical Research, University of Castilla-La Mancha, Albacete, Spain.,Department of Psychology, University of Area Andina, Bogotá, Colombia
| | | | - Francisco Mansilla
- Radiology Service, Sta. Cristina Clinic and University Hospital of Albacete, Albacete, Spain
| | - Andres Martínez
- Neonatology Service, University Hospital of Albacete, Albacete, Spain
| | - Ignacio Onsurbe
- Paediatric Neurology Service, University Hospital of Albacete, Albacete, Spain
| | - Paloma San Roman
- Child Psychiatry Service, University Hospital of Albacete, Albacete, Spain
| | - Mar Ubero-Martinez
- Human Neuroanatomy Laboratory, School of Medicine and Regional Centre for Biomedical Research, University of Castilla-La Mancha, Albacete, Spain.,Department of Anatomy, Catholic University of Murcia, Murcia, Spain
| | - Jonathan D Clayden
- Developmental Imaging and Biophysics Section, Institute of Child Health, University College London, London, United Kingdom
| | - Chris A Clark
- Developmental Imaging and Biophysics Section, Institute of Child Health, University College London, London, United Kingdom
| | - Mónica Muñoz-López
- Human Neuroanatomy Laboratory, School of Medicine and Regional Centre for Biomedical Research, University of Castilla-La Mancha, Albacete, Spain.,Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
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Brain microstructural development in neonates with critical congenital heart disease: An atlas-based diffusion tensor imaging study. NEUROIMAGE-CLINICAL 2019; 21:101672. [PMID: 30677732 PMCID: PMC6350221 DOI: 10.1016/j.nicl.2019.101672] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 12/30/2018] [Accepted: 01/07/2019] [Indexed: 11/29/2022]
Abstract
Background Brain microstructural maturation progresses rapidly in the third trimester of gestation and first weeks of life, but typical microstructural development may be influenced by the presence of critical congenital heart disease (CHD). Objective The aim of this study was to investigate the pattern of white matter (WM) microstructural development in neonates with different types of critical CHD. The secondary aim was to examine whether there is an association between WM microstructural maturity and neonatal ischemic brain injury. Methods For this prospective, longitudinal cohort study, 74 term born neonates underwent diffusion tensor imaging (DTI) before (N = 56) and after (N = 71) cardiac surgery performed <30 days of life for transposition of the great arteries (TGA), single ventricle physiology with aortic arch obstruction (SVP-AO), left- (LVOTO) or right ventricle outflow tract obstruction (RVOTO). Microstructural integrity was investigated by fractional anisotropy (FA) and by mean diffusivity (MD) in 16 white matter (WM) structures in three WM regions with correction for postmenstrual age. Ischemic brain injury was defined as moderate-severe white matter injury or stroke. Results Before cardiac surgery, the posterior parts of the corona radiata and internal capsule showed significantly higher FA and lower MD compared to the anterior parts. Centrally-located WM structures demonstrated higher FA compared to peripherally-located structures. Neonates with TGA had higher FA in projection-, association- and commissural WM before surgery, when compared to other CHD groups. Neonates with LVOTO showed lower preoperative MD in these regions, and neonates with SVP-AO higher MD. Differences in FA/MD between CHD groups were most clear in centrally located WM structures. Between CHD groups, no differences in postoperative FA/MD or in change from pre- to postoperative FA/MD were seen. Neonatal ischemic brain injury was not associated with pre- or postoperative FA/MD. Conclusions Collectively, these findings revealed brain microstructural WM development to follow the same organized pattern in critical CHD as reported in healthy and preterm neonates, from posterior-to-anterior and central-to-peripheral. Neonates with TGA and LVOTO showed the most mature WM microstructure before surgery and SVP-AO the least mature. Degree of WM microstructural immaturity was not associated with ischemic brain injury.
Preoperative white matter integrity related to critical CHD type. Largest difference across CHD types in most mature white matter structures. Pattern of white matter development not related to critical CHD type. White matter maturity not related to higher risk neonatal ischemic brain injury.
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Glass TJ, Seed M, Chau V. Congenital Heart Disease. Neurology 2019. [DOI: 10.1016/b978-0-323-54392-7.00015-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Leijser LM, de Vries LS. Preterm brain injury: Germinal matrix-intraventricular hemorrhage and post-hemorrhagic ventricular dilatation. HANDBOOK OF CLINICAL NEUROLOGY 2019; 162:173-199. [PMID: 31324310 DOI: 10.1016/b978-0-444-64029-1.00008-4] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Germinal matrix hemorrhage and intraventricular hemorrhages (GMH-IVH) remain a common and clinically significant problem in preterm infants, particularly extremely preterm infants. A large GMH-IVH is often complicated by posthemorrhagic ventricular dilation (PHVD) or parenchymal hemorrhagic infarction and is associated with an increased risk of adverse neurologic sequelae. The widespread use of cranial ultrasonography since the early 1980s has shown a gradual decrease in the incidence of GMH-IVH and has helped with the identification of antenatal and perinatal risk factors and timing of the lesion. The increased use of magnetic resonance imaging (MRI) has contributed to more detailed visualization of the site and extent of the GMH-IVH. In addition, MRI has contributed to the awareness of associated white matter changes as well as associated cerebellar hemorrhages. Although GMH-IVH and PHVD still cannot be prevented, cerebrospinal fluid drainage initiated in the early stage of PHVD development seems to be associated with a better neurodevelopmental outcome. Further studies are underway to improve treatment strategies for PHVD and to potentially prevent and repair GMH-IVH and PHVD and associated brain injury. This chapter discusses the pathogenesis, incidence, risk factors, and management, including preventive measures, of GHM-IVH and PHVD.
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Affiliation(s)
- Lara M Leijser
- Department of Pediatrics, Section of Neonatology, University of Calgary, Cumming School of Medicine, Calgary, Canada
| | - Linda S de Vries
- Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands.
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Counsell SJ, Arichi T, Arulkumaran S, Rutherford MA. Fetal and neonatal neuroimaging. HANDBOOK OF CLINICAL NEUROLOGY 2019; 162:67-103. [PMID: 31324329 DOI: 10.1016/b978-0-444-64029-1.00004-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Magnetic resonance imaging (MRI) can provide detail of the soft tissues of the fetal and neonatal brain that cannot be obtained by any other imaging modality. Conventional T1 and T2 weighted sequences provide anatomic detail of the normally developing brain and can demonstrate lesions, including those associated with preterm birth, hypoxic ischemic encephalopathy, perinatal arterial stroke, infections, and congenital malformations. Specialized imaging techniques can be used to assess cerebral vasculature (magnetic resonance angiography and venography), cerebral metabolism (magnetic resonance spectroscopy), cerebral perfusion (arterial spin labeling), and function (functional MRI). A wealth of quantitative tools, most of which were originally developed for the adult brain, can be applied to study the developing brain in utero and postnatally including measures of tissue microstructure obtained from diffusion MRI, morphometric studies to measure whole brain and regional tissue volumes, and automated approaches to study cortical folding. In this chapter, we aim to describe different imaging approaches for the fetal and neonatal brain, and to discuss their use in a range of clinical applications.
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Affiliation(s)
- Serena J Counsell
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom.
| | - Tomoki Arichi
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
| | - Sophie Arulkumaran
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
| | - Mary A Rutherford
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
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White matter injury predicts disrupted functional connectivity and microstructure in very preterm born neonates. NEUROIMAGE-CLINICAL 2018; 21:101596. [PMID: 30458986 PMCID: PMC6411591 DOI: 10.1016/j.nicl.2018.11.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 10/26/2018] [Accepted: 11/12/2018] [Indexed: 11/28/2022]
Abstract
Objective To determine whether the spatial extent and location of early-identified punctate white matter injury (WMI) is associated with regionally-specific disruptions in thalamocortical-connectivity in very-preterm born neonates. Methods 37 very-preterm born neonates (median gestational age: 28.1 weeks; interquartile range [IQR]: 27–30) underwent early MRI (median age 32.9 weeks; IQR: 32–35), and WMI was identified in 13 (35%) neonates. Structural T1-weighted, resting-state functional Magnetic Resonance Imaging (rs-fMRI, n = 34) and Diffusion Tensor Imaging (DTI, n = 31) sequences were acquired using 3 T-MRI. A probabilistic map of WMI was developed for the 13 neonates demonstrating brain injury. A neonatal atlas was applied to the WMI maps, rs-fMRI and DTI analyses to extract volumetric, functional and microstructural data from regionally-specific brain areas. Associations of thalamocortical-network strength and alterations in fractional anisotropy (FA, a measure of white-matter microstructure) with WMI volume were assessed in general linear models, adjusting for age at scan and cerebral volumes. Results WMI volume in the superior (β = −0.007; p = .02) and posterior corona radiata (β = −0.01; p = .01), posterior thalamic radiations (β = −0.01; p = .005) and superior longitudinal fasciculus (β = −0.02; p = .001) was associated with reduced connectivity strength between thalamus and parietal resting-state networks. WMI volume in the left (β = −0.02; p = .02) and right superior corona radiata (β = −0.03; p = .008), left posterior corona radiata (β = −0.03; p = .01), corpus callosum (β = −0.11; p < .0001) and right superior longitudinal fasciculus (β = −0.02; p = .02) was associated with functional connectivity strength between thalamic and sensorimotor networks. Increased WMI volume was also associated with decreased FA values in the corpus callosum (β = −0.004, p = .015). Conclusions Regionally-specific alterations in early functional and structural network complexity resulting from WMI may underlie impaired outcomes.
Lesions in white matter pathways predicted altered functional connectivity. White matter lesions predicted alterations in white matter microstructure. Findings of lesion location and size were regionally-specific. White matter lesion size and location may underlie later delays in development.
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Katorza E, Strauss G, Cohen R, Berkenstadt M, Hoffmann C, Achiron R, Barzilay E, Bar-Yosef O. Apparent Diffusion Coefficient Levels and Neurodevelopmental Outcome in Fetuses with Brain MR Imaging White Matter Hyperintense Signal. AJNR Am J Neuroradiol 2018; 39:1926-1931. [PMID: 30190257 DOI: 10.3174/ajnr.a5802] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 07/19/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND PURPOSE One of the perplexing findings of fetal brain MR imaging is white matter T2 hyperintense signal. The aims of our study were initially to determine the main etiologies associated with white matter T2 hyperintense signal, then to examine whether the different etiologies have different ADC values, and, last, to assess the association of white matter T2 hyperintense signal with developmental outcome. MATERIALS AND METHODS This was a prospective cohort study of 44 MR imaging scans of fetal brains obtained for suspected brain pathologies at a tertiary medical center during 2011-2015. Clinical data were collected from electronic medical charts. ADC values were measured and averaged in the frontal, parietal, occipital, and temporal lobes. Neurodevelopmental assessments were performed with the Vineland Adaptive Behavior Scales II. RESULTS Half of the cases of MRI hyperintense T2 signal of the fetal brain were associated with congenital cytomegalovirus infection. The other half were mainly idiopathic. Thus, the study group was divided to subgroups positive and negative for cytomegalovirus. Both groups had hyperintense signal in the temporal lobe. The group positive for cytomegalovirus had involvement of the parietal lobe. Only this group had increased ADC values in the temporal and parietal lobes. There was no association between the neurodevelopment outcome and the etiologies or ADC values. CONCLUSIONS T2 hyperintense signal in fetal brain MRI associated with positive cytomegalovirus infection has increased ADC values in the temporal and parietal lobes, suggestive of brain edema in these areas. However, the association between this finding and neurodevelopment outcome requires further evaluation.
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Affiliation(s)
- E Katorza
- From the Antenatal Diagnostic Unit (E.K., G.S., R.C., R.A., E.B.).,Sackler School of Medicine (E.K., G.S., R.C., M.B., C.H., R.A., E.B., O.B.-Y.), Tel Aviv University, Tel Aviv, Israel
| | - G Strauss
- From the Antenatal Diagnostic Unit (E.K., G.S., R.C., R.A., E.B.).,Sackler School of Medicine (E.K., G.S., R.C., M.B., C.H., R.A., E.B., O.B.-Y.), Tel Aviv University, Tel Aviv, Israel
| | - R Cohen
- From the Antenatal Diagnostic Unit (E.K., G.S., R.C., R.A., E.B.).,Sackler School of Medicine (E.K., G.S., R.C., M.B., C.H., R.A., E.B., O.B.-Y.), Tel Aviv University, Tel Aviv, Israel
| | - M Berkenstadt
- The Danek Gertner Institute of Human Genetics (M.B.).,Sackler School of Medicine (E.K., G.S., R.C., M.B., C.H., R.A., E.B., O.B.-Y.), Tel Aviv University, Tel Aviv, Israel
| | - C Hoffmann
- Neuroradiology Unit (C.H.), Department of Diagnostic Radiology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.,Sackler School of Medicine (E.K., G.S., R.C., M.B., C.H., R.A., E.B., O.B.-Y.), Tel Aviv University, Tel Aviv, Israel
| | - R Achiron
- From the Antenatal Diagnostic Unit (E.K., G.S., R.C., R.A., E.B.).,Sackler School of Medicine (E.K., G.S., R.C., M.B., C.H., R.A., E.B., O.B.-Y.), Tel Aviv University, Tel Aviv, Israel
| | - E Barzilay
- From the Antenatal Diagnostic Unit (E.K., G.S., R.C., R.A., E.B.).,Sackler School of Medicine (E.K., G.S., R.C., M.B., C.H., R.A., E.B., O.B.-Y.), Tel Aviv University, Tel Aviv, Israel
| | - O Bar-Yosef
- Department of Obstetrics and Gynecology, Pediatric Neurology Unit (O.B.-Y.) .,Sackler School of Medicine (E.K., G.S., R.C., M.B., C.H., R.A., E.B., O.B.-Y.), Tel Aviv University, Tel Aviv, Israel
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Pecheva D, Kelly C, Kimpton J, Bonthrone A, Batalle D, Zhang H, Counsell SJ. Recent advances in diffusion neuroimaging: applications in the developing preterm brain. F1000Res 2018; 7. [PMID: 30210783 PMCID: PMC6107996 DOI: 10.12688/f1000research.15073.1] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/17/2018] [Indexed: 12/13/2022] Open
Abstract
Measures obtained from diffusion-weighted imaging provide objective indices of white matter development and injury in the developing preterm brain. To date, diffusion tensor imaging (DTI) has been used widely, highlighting differences in fractional anisotropy (FA) and mean diffusivity (MD) between preterm infants at term and healthy term controls; altered white matter development associated with a number of perinatal risk factors; and correlations between FA values in the white matter in the neonatal period and subsequent neurodevelopmental outcome. Recent developments, including neurite orientation dispersion and density imaging (NODDI) and fixel-based analysis (FBA), enable white matter microstructure to be assessed in detail. Constrained spherical deconvolution (CSD) enables multiple fibre populations in an imaging voxel to be resolved and allows delineation of fibres that traverse regions of fibre-crossings, such as the arcuate fasciculus and cerebellar–cortical pathways. This review summarises DTI findings in the preterm brain and discusses initial findings in this population using CSD, NODDI, and FBA.
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Affiliation(s)
- Diliana Pecheva
- Centre for the Developing Brain, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK
| | - Christopher Kelly
- Centre for the Developing Brain, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK
| | - Jessica Kimpton
- Centre for the Developing Brain, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK
| | - Alexandra Bonthrone
- Centre for the Developing Brain, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK
| | - Dafnis Batalle
- Centre for the Developing Brain, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK
| | - Hui Zhang
- Department of Computer Science & Centre for Medical Image Computing, University College London, London, UK
| | - Serena J Counsell
- Centre for the Developing Brain, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK
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Sorokan ST, Jefferies AL, Miller SP. L’imagerie du cerveau du nouveau-né à terme. Paediatr Child Health 2018. [DOI: 10.1093/pch/pxy002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- S Todd Sorokan
- Société canadienne de pédiatrie, comité d’étude du fœtus et du nouveau-né, Ottawa (Ontario)
| | - Ann L Jefferies
- Société canadienne de pédiatrie, comité d’étude du fœtus et du nouveau-né, Ottawa (Ontario)
| | - Steven P Miller
- Société canadienne de pédiatrie, comité d’étude du fœtus et du nouveau-né, Ottawa (Ontario)
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Abstract
Brain imaging is important for the diagnosis and management of sick term neonates. Although ultrasound and computed tomography may provide some information, magnetic resonance imaging is now the brain imaging modality of choice because it is the most sensitive technique for detecting and quantifying brain abnormalities and does not expose infants to radiation. This statement describes the principles, roles and limitations of these three imaging modalities and makes recommendations for appropriate use in term neonates. The primary focus is the brain of term infants with neonatal encephalopathy, many of whom are diagnosed with hypoxic-ischemic encephalopathy.
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Affiliation(s)
- S Todd Sorokan
- Canadian Paediatric Society, Fetus and Newborn Committee, Ottawa, Ontario
| | - Ann L Jefferies
- Canadian Paediatric Society, Fetus and Newborn Committee, Ottawa, Ontario
| | - Steven P Miller
- Canadian Paediatric Society, Fetus and Newborn Committee, Ottawa, Ontario
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Teli R, Hay M, Hershey A, Kumar M, Yin H, Parikh NA. Postnatal Microstructural Developmental Trajectory of Corpus Callosum Subregions and Relationship to Clinical Factors in Very Preterm Infants. Sci Rep 2018; 8:7550. [PMID: 29765059 PMCID: PMC5954149 DOI: 10.1038/s41598-018-25245-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 04/13/2018] [Indexed: 11/30/2022] Open
Abstract
Our objectives were to define the microstructural developmental trajectory of six corpus callosum subregions and identify perinatal clinical factors that influence early development of these subregions in very preterm infants. We performed a longitudinal cohort study of very preterm infants (32 weeks gestational age or younger) (N = 36) who underwent structural MRI and diffusion tensor imaging serially at four time points - before 32, 32, 38, and 52 weeks postmenstrual age. We divided the corpus callosum into six subregions, performed probabilistic tractography, and used linear mixed effects models to evaluate the influence of antecedent clinical factors on its microstructural growth trajectory. The genu and splenium demonstrated the most rapid developmental maturation, exhibited by a steep increase in fractional anisotropy. We identified several factors that favored greater corpus callosum microstructural development, including advancing postmenstrual age, higher birth weight, and college level or higher maternal education. Bronchopulmonary dysplasia, low 5-minute Apgar scores, caffeine therapy/apnea of prematurity and male sex were associated with reduced corpus callosum microstructural integrity/development over the first six months after very preterm birth. We identified a unique postnatal microstructural growth trajectory and associated clinical factor profile for each of the six corpus callosum subregions that is consistent with the heterogeneous functional role of these white matter subregions.
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Affiliation(s)
- Radhika Teli
- Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
| | - Margaret Hay
- Center for Perinatal Research, Nationwide Children's Hospital, Columbus, Ohio, United States of America
| | - Alexa Hershey
- Center for Perinatal Research, Nationwide Children's Hospital, Columbus, Ohio, United States of America
| | - Manoj Kumar
- Center for Perinatal Research, Nationwide Children's Hospital, Columbus, Ohio, United States of America
| | - Han Yin
- Center for Perinatal Research, Nationwide Children's Hospital, Columbus, Ohio, United States of America
| | - Nehal A Parikh
- Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America. .,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America. .,Center for Perinatal Research, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
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Multiple Postnatal Infections in Newborns Born Preterm Predict Delayed Maturation of Motor Pathways at Term-Equivalent Age with Poorer Motor Outcomes at 3 Years. J Pediatr 2018; 196:91-97.e1. [PMID: 29398063 DOI: 10.1016/j.jpeds.2017.12.041] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Revised: 11/21/2017] [Accepted: 12/15/2017] [Indexed: 01/08/2023]
Abstract
OBJECTIVES To evaluate whether the number of postnatal infections is associated with abnormal white matter maturation and poorer motor neurodevelopmental outcomes at 36 months of corrected age. STUDY DESIGN A prospective longitudinal cohort study was undertaken of 219 newborns born preterm at 24-32 weeks of gestational age recruited between 2006 and 2013 with magnetic resonance imaging of the brain both early in life and at term-equivalent age. Postnatal infection was defined as any clinical infection or positive culture ≥72 hours after birth. White matter maturation was assessed by magnetic resonance spectroscopic imaging, magnetic resonance diffusion tensor imaging, and tract-based spatial statistics. Neurodevelopmental outcomes were assessed in 175 (82% of survivors) infants with Bayley Scales of Infant and Toddler Development-III composite scores and Peabody Developmental Motor Scales at 35 months of corrected age (IQR 34-37 months). Infection groups were compared via the Fisher exact test, Kruskal-Wallis test, and generalized estimating equations. RESULTS Of 219 neonates born preterm (median gestational age 27.9 weeks), 109 (50%) had no postnatal infection, 83 (38%) had 1 or 2 infections, and 27 (12%) had ≥3 infections. Infants with postnatal infections had more cerebellar hemorrhage. Infants with ≥3 infections had lower N-acetylaspartate/choline in the white matter and basal ganglia regions, lower fractional anisotropy in the posterior limb of the internal capsule, and poorer maturation of the corpus callosum, optic radiations, and posterior limb of the internal capsule on tract-based spatial statistics analysis as well as poorer Bayley Scales of Infant and Toddler Development-III (P = .02) and Peabody Developmental Motor Scales, Second Edition, motor scores (P < .01). CONCLUSIONS In newborns born preterm, ≥3 postnatal infections predict impaired development of the motor pathways and poorer motor outcomes in early childhood.
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Leijser LM, Miller SP, van Wezel-Meijler G, Brouwer AJ, Traubici J, van Haastert IC, Whyte HE, Groenendaal F, Kulkarni AV, Han KS, Woerdeman PA, Church PT, Kelly EN, van Straaten HLM, Ly LG, de Vries LS. Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene? Neurology 2018; 90:e698-e706. [PMID: 29367448 DOI: 10.1212/wnl.0000000000004984] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 11/06/2017] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an "early approach" (EA), based on ventricular measurements exceeding normal (ventricular index [VI] <+2 SD/anterior horn width <6 mm) with initial temporizing procedures, followed, if needed, by permanent shunt placement, and a "late approach" (LA), based on signs of increased intracranial pressure with mostly immediate permanent intervention. METHODS Observational cohort study of 127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or LA (n = 49). Ventricular size was measured on cranial ultrasound. Outcome was assessed at 18-24 months. RESULTS Forty-nine of 78 (63%) EA and 24 of 49 (49%) LA infants received intervention. LA infants were slightly younger at birth, but did not differ from EA infants for other clinical measures. Initial intervention in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p < 0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted predominantly of lumbar punctures or reservoir taps. Maximum VI in infants with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p < 0.001) and complications were lower in EA than LA group. Most EA infants had normal outcomes (>-1 SD), despite intervention. LA infants with intervention had poorer outcomes than those without (p < 0.003), with scores <-2 SD in 81%. CONCLUSION In preterm infants with PHVD, those with early intervention, even when eventually requiring a shunt, had outcomes indistinguishable from those without intervention, all being within the normal range. In contrast, in infants managed with LA, need for intervention predicted worse outcomes. Benefits of EA appear to outweigh potential risks. CLASSIFICATION OF EVIDENCE This study provides Class III evidence that for preterm infants with PHVD, an EA to management results in better neurodevelopmental outcomes than a LA.
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Affiliation(s)
- Lara M Leijser
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Steven P Miller
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Gerda van Wezel-Meijler
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Annemieke J Brouwer
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Jeffrey Traubici
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Ingrid C van Haastert
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Hilary E Whyte
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Floris Groenendaal
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Abhaya V Kulkarni
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Kuo S Han
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Peter A Woerdeman
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Paige T Church
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Edmond N Kelly
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Henrica L M van Straaten
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Linh G Ly
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada
| | - Linda S de Vries
- From the Divisions of Neonatology (L.M.L., H.E.W., L.G.L.), Neurology (L.M.L., S.P.M.), and Neurosurgery (A.V.K.), Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, Canada; Department of Neonatology (G.v.W.-M., H.L.M.v.S.), Isala Women-Children's Hospital, Zwolle, the Netherlands; Department of Neonatology (A.J.B., I.C.v.H., F.G., L.S.d.V.), Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands; University of Applied Sciences (A.J.B.), Utrecht, the Netherlands; Department of Radiology (J.T.), The Hospital for Sick Children and The University of Toronto, Canada; Department of Neurology and Neurosurgery (K.S.H., P.A.W.), University Medical Center Utrecht, the Netherlands; Department of Newborn and Developmental Pediatrics (P.T.C.), Sunnybrook Health Sciences Centre and The University of Toronto; and Division of Neonatology (E.N.K.), Department of Pediatrics, Mount Sinai Hospital and The University of Toronto, Canada.
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Neubauer V, Djurdjevic T, Griesmaier E, Biermayr M, Gizewski ER, Kiechl-Kohlendorfer U. The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage. Neonatology 2018; 113:93-99. [PMID: 29131075 DOI: 10.1159/000480695] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Accepted: 08/26/2017] [Indexed: 11/19/2022]
Abstract
BACKGROUND Recent advances in magnetic resonance imaging (MRI) techniques have prompted reconsideration of the anatomical correlates of adverse outcomes in preterm infants. The importance of the contribution made by the cerebellum is now increasingly appreciated. The effect of cerebellar haemorrhage (CBH) on the microstructure of the cerebellar-cerebral circuit is largely unexplored. OBJECTIVES To investigate the effect of CBH on the microstructure of cerebellar-cerebral connections in preterm infants aged <32 gestational weeks. METHODS Infants underwent diffusion tensor MRI at term-equivalent age. MRI was evaluated for CBH and additional supratentorial brain injury using a validated scoring system. Region of interest-based measures of brain microstructure (fractional anisotropy [FA] and apparent diffusion coefficient) were quantified in 5 vulnerable regions (the centrum semiovale, posterior limb of the internal capsule, corpus callosum, and superior and middle cerebellar peduncles). Group differences between infants with CBH and infants without CBH were assessed. RESULTS There were 267 infants included in the study. Infants with CBH (isolated and combined) had significantly lower FA values in all regions investigated. Infants with isolated CBH showed lower FA in the middle and superior cerebellar peduncles and in the posterior limb of the internal capsule. CONCLUSIONS This study provides evidence that CBH causes alterations in localised and remote WM pathways in the developing brain. The disruption of the cerebellar-cerebral microstructure at multiple sites adds further support for the concept of developmental diaschisis, which is propagated as an explanation for the consequences of early cerebellar injury on cognitive and affective domains.
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Affiliation(s)
- Vera Neubauer
- Department of Paediatrics II, Neonatology, Medical University of Innsbruck, Innsbruck, Austria
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Glass TJA, Chau V, Gardiner J, Foong J, Vinall J, Zwicker JG, Grunau RE, Synnes A, Poskitt KJ, Miller SP. Severe retinopathy of prematurity predicts delayed white matter maturation and poorer neurodevelopment. Arch Dis Child Fetal Neonatal Ed 2017; 102:F532-F537. [PMID: 28536205 DOI: 10.1136/archdischild-2016-312533] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 04/04/2017] [Accepted: 04/06/2017] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months' corrected age (CA) compared with neonates without severe ROP. DESIGN We conducted a prospective longitudinal cohort of extremely preterm neonates born 24-28 weeks' gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months' CA. Subjects were compared using Fisher's exact, Kruskal-Wallis and generalised estimating equations. SETTING Families were recruited from the neonatal intensive care unit at BC Women's Hospital. PATIENTS Of 98 extremely preterm neonates (median: 26.0 weeks) assessed locally for ROP, 19 (19%) had severe ROP and 83 (85%) were assessed at 18 months' CA. RESULTS Severe ROP was associated with lower FA in the posterior white matter, and with decreased measures of brain maturation in the optic radiations, posterior limb of the internal capsule (PLIC) and external capsule on TBSS. Bayley-III cognitive and motor scores were lower in infants with severe ROP. CONCLUSIONS Severe ROP is associated with maturational delay in the optic radiations, PLIC, external capsule and posterior white matter, housing the primary visual and motor pathways, and is associated with poorer cognitive and motor outcomes at 18 months' CA.
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Affiliation(s)
- Torin J A Glass
- Department of Pediatrics (Neurology), University of Toronto and the Hospital for Sick Children, Toronto, Canada.,Neurosciences & Mental Health, SickKids Research Institute, Toronto, Canada
| | - Vann Chau
- Department of Pediatrics (Neurology), University of Toronto and the Hospital for Sick Children, Toronto, Canada.,Neurosciences & Mental Health, SickKids Research Institute, Toronto, Canada.,BC Children's Hospital Research Institute, Vancouver, Canada
| | - Jane Gardiner
- BC Children's Hospital Research Institute, Vancouver, Canada.,Department of Ophthalmology and Vision Science, University of British Columbia and BC Children's Hospital, Vancouver, Canada
| | - Justin Foong
- Neurosciences & Mental Health, SickKids Research Institute, Toronto, Canada
| | - Jillian Vinall
- Department of Anesthesiology, University of Calgary, Calgary, Canada
| | - Jill G Zwicker
- BC Children's Hospital Research Institute, Vancouver, Canada.,Department of Pediatrics (Developmental Pediatrics), University of British Columbia and BC Children's and Women's Hospitals, Vancouver, Canada.,Department of Occupational Science and Occupational Therapy, Vancouver, Canada.,Sunny Hill Health Centre for Children, Vancouver, Canada
| | - Ruth E Grunau
- BC Children's Hospital Research Institute, Vancouver, Canada.,Department of Pediatrics (Neonatology), University of British Columbia and BC Children's and Women's Hospitals, Vancouver, Canada
| | - Anne Synnes
- BC Children's Hospital Research Institute, Vancouver, Canada.,Department of Pediatrics (Neonatology), University of British Columbia and BC Children's and Women's Hospitals, Vancouver, Canada
| | - Kenneth J Poskitt
- BC Children's Hospital Research Institute, Vancouver, Canada.,Department of Radiology, University of British Columbia and BC Children's Hospital, Vancouver, Canada
| | - Steven P Miller
- Department of Pediatrics (Neurology), University of Toronto and the Hospital for Sick Children, Toronto, Canada.,Neurosciences & Mental Health, SickKids Research Institute, Toronto, Canada.,BC Children's Hospital Research Institute, Vancouver, Canada
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Back SA. White matter injury in the preterm infant: pathology and mechanisms. Acta Neuropathol 2017; 134:331-349. [PMID: 28534077 PMCID: PMC5973818 DOI: 10.1007/s00401-017-1718-6] [Citation(s) in RCA: 317] [Impact Index Per Article: 39.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 04/27/2017] [Accepted: 04/29/2017] [Indexed: 12/22/2022]
Abstract
The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in the care of preterm infants have resulted in a sustained reduction in the severity of WMI that has shifted from more severe focal necrotic lesions to milder diffuse WMI. Nevertheless, WMI remains a global health problem and the most common cause of chronic neurological morbidity from cerebral palsy and diverse neurobehavioral disabilities. Diffuse WMI involves maturation-dependent vulnerability of the oligodendrocyte (OL) lineage with selective degeneration of late oligodendrocyte progenitors (preOLs) triggered by oxidative stress and other insults. The magnitude and distribution of diffuse WMI are related to both the timing of appearance and regional distribution of susceptible preOLs. Diffuse WMI disrupts the normal progression of OL lineage maturation and myelination through aberrant mechanisms of regeneration and repair. PreOL degeneration is accompanied by early robust proliferation of OL progenitors that regenerate and augment the preOL pool available to generate myelinating OLs. However, newly generated preOLs fail to differentiate and initiate myelination along their normal developmental trajectory despite the presence of numerous intact-appearing axons. Disrupted preOL maturation is accompanied by diffuse gliosis and disturbances in the composition of the extracellular matrix and is mediated in part by inhibitory factors derived from reactive astrocytes. Signaling pathways implicated in disrupted myelination include those mediated by Notch, WNT-beta catenin, and hyaluronan. Hence, there exists a potentially broad but still poorly defined developmental window for interventions to promote white matter repair and myelination and potentially reverses the widespread disturbances in cerebral gray matter growth that accompanies WMI.
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Affiliation(s)
- Stephen A Back
- Division of Pediatric Neuroscience, Departments of Pediatrics and Neurology, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd, Portland, OR, 97239-3098, USA.
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Kotovich D, Guedalia JSB, Hoffmann C, Sze G, Eisenkraft A, Yaniv G. Apparent Diffusion Coefficient Value Changes and Clinical Correlation in 90 Cases of Cytomegalovirus-Infected Fetuses with Unremarkable Fetal MRI Results. AJNR Am J Neuroradiol 2017; 38:1443-1448. [PMID: 28522662 DOI: 10.3174/ajnr.a5222] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 03/06/2017] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE Cytomegalovirus is the leading intrauterine infection. Fetal MR imaging is an accepted tool for fetal brain evaluation, yet it still lacks the ability to accurately predict the extent of the neurodevelopmental impairment, especially in fetal MR imaging scans with unremarkable findings. Our hypothesis was that intrauterine cytomegalovirus infection causes diffusional changes in fetal brains and that those changes may correlate with the severity of neurodevelopmental deficiencies. MATERIALS AND METHODS A retrospective analysis was performed on 90 fetal MR imaging scans of cytomegalovirus-infected fetuses with unremarkable results and compared with a matched gestational age control group of 68 fetal head MR imaging scans. ADC values were measured and averaged in the frontal, parietal, occipital, and temporal lobes; basal ganglia; thalamus; and pons. For neurocognitive assessment, the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) was used on 58 children in the cytomegalovirus-infected group. RESULTS ADC values were reduced for the cytomegalovirus-infected fetuses in most brain areas studied. The VABS-II showed no trend for the major domains or the composite score of the VABS-II for the cytomegalovirus-infected children compared with the healthy population distribution. Some subdomains showed an association between ADC values and VABS-II scores. CONCLUSIONS Cytomegalovirus infection causes diffuse reduction in ADC values in the fetal brain even in unremarkable fetal MR imaging scans. Cytomegalovirus-infected children with unremarkable fetal MR imaging scans do not deviate from the healthy population in the VABS-II neurocognitive assessment. ADC values were not correlated with VABS-II scores. However, the lack of clinical findings, as seen in most cytomegalovirus-infected fetuses, does not eliminate the possibility of future neurodevelopmental pathology.
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Affiliation(s)
- D Kotovich
- From The Faculty of Medicine (D.K., A.E.), Institute for Research in Military Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- The Israel Defense Forces Medical Corps (D.K., A.E.), Chevy Chase, Maryland
| | - J S B Guedalia
- Neuropsychology Unit (J.S.B.G., G.Y.), Shaare Zedek Medical Center, Jerusalem, Israel
| | | | - G Sze
- Department of Radiology and Biomedical Imaging (G.S., G.Y.), Yale School of Medicine, New Haven, Connecticut
| | - A Eisenkraft
- From The Faculty of Medicine (D.K., A.E.), Institute for Research in Military Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- The Israel Defense Forces Medical Corps (D.K., A.E.), Chevy Chase, Maryland
| | - G Yaniv
- Neuropsychology Unit (J.S.B.G., G.Y.), Shaare Zedek Medical Center, Jerusalem, Israel
- Dr. Pinchas Bornstein Talpiot Medical Leadership Program (G.Y.), Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel
- Department of Radiology and Biomedical Imaging (G.S., G.Y.), Yale School of Medicine, New Haven, Connecticut
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Li X, Gao J, Wang M, Zheng J, Li Y, Hui ES, Wan M, Yang J. Characterization of Extensive Microstructural Variations Associated with Punctate White Matter Lesions in Preterm Neonates. AJNR Am J Neuroradiol 2017; 38:1228-1234. [PMID: 28450434 PMCID: PMC7960104 DOI: 10.3174/ajnr.a5226] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 01/26/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND PURPOSE Punctate white matter lesions are common in preterm neonates. Neurodevelopmental outcomes of the neonates are related to the degree of extension. This study aimed to characterize the extent of microstructural variations for different punctate white matter lesion grades. MATERIALS AND METHODS Preterm neonates with punctate white matter lesions were divided into 3 grades (from mild to severe: grades I-III). DTI-derived fractional anisotropy, axial diffusivity, and radial diffusivity between patients with punctate white matter lesions and controls were compared with Tract-Based Spatial Statistics and tract-quantification methods. RESULTS Thirty-three preterm neonates with punctate white matter lesions and 33 matched controls were enrolled. There were 15, 9, and 9 patients, respectively, in grades I, II, and III. Punctate white matter lesions were mainly located in white matter adjacent to the lateral ventricles, especially regions lateral to the trigone, posterior horns, and centrum semiovale and/or corona radiata. Extensive microstructural changes were observed in neonates with grade III punctate white matter lesions, while no significant changes in DTI metrics were found for grades I and II. A pattern of increased axial diffusivity, increased radial diffusivity, and reduced/unchanged fractional anisotropy was found in regions adjacent to punctate white matter lesion sites seen on T1WI and T2WI. Unchanged axial diffusivity, increased radial diffusivity, and reduced/unchanged fractional anisotropy were observed in regions distant from punctate white matter lesion sites. CONCLUSIONS White matter microstructural variations were different across punctate white matter lesion grades. Extensive change patterns varied according to the distance to the lesion sites in neonates with severe punctate white matter lesions. These findings may help in determining the outcomes of punctate white matter lesions and selecting treatment strategies.
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Affiliation(s)
- X Li
- From the Department of Radiology (X.L., J.G., M. Wang, Y.L., J.Y.)
- Department of Biomedical Engineering (X.L., M. Wan, J.Y.), the Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - J Gao
- From the Department of Radiology (X.L., J.G., M. Wang, Y.L., J.Y.)
| | - M Wang
- From the Department of Radiology (X.L., J.G., M. Wang, Y.L., J.Y.)
| | - J Zheng
- Clinical Research Center (J.Z.), the First Affiliated Hospital, Xi'an, Shaanxi, China
| | - Y Li
- From the Department of Radiology (X.L., J.G., M. Wang, Y.L., J.Y.)
| | - E S Hui
- Department of Diagnostic Radiology (E.S.H.), University of Hong Kong, Hong Kong, China
| | - M Wan
- Department of Biomedical Engineering (X.L., M. Wan, J.Y.), the Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - J Yang
- From the Department of Radiology (X.L., J.G., M. Wang, Y.L., J.Y.)
- Department of Biomedical Engineering (X.L., M. Wan, J.Y.), the Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
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Bültmann E, Mußgnug HJ, Zapf A, Hartmann H, Nägele T, Lanfermann H. Changes in brain microstructure during infancy and childhood using clinical feasible ADC-maps. Childs Nerv Syst 2017; 33:735-745. [PMID: 28364169 DOI: 10.1007/s00381-017-3391-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 03/17/2017] [Indexed: 11/27/2022]
Abstract
PURPOSE The purpose of this study was to examine age-related changes in apparent diffusion coefficient (ADC) during infancy and childhood using routine MRI data. METHODS A total of 112 investigations of patients aged 0 to 17.2 years showing a normal degree of myelination and no signal abnormalities on conventional MRI were retrospectively selected from our pool of pediatric MRI examinations at 1.5T. ADC maps based on our routinely included axial diffusion weighted sequence were created from the scanner. ADC values were measured in 35 different brain regions investigating normal age-related changes during the maturation of the human brain in infancy and childhood using clinical feasible sequences at 1.5T. RESULTS The relationship between ADC values and age in infancy and childhood can be described as an exponential function. With increasing age, the ADC values decrease significantly in all brain regions, especially during the first 2 years of life. Except in the peritrigonal white matter, no significant differences were found between both hemispheres. Between 0 and 2 years of life, no significant gender differences were detected. CONCLUSIONS Using ADC maps based on a routinely performed axial diffusion weighted sequence, it was possible first to describe the relationship between ADC values and age in infancy and childhood as exponential function in the whole brain and second to determine normative age-related ADC values in multiple brain regions.
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Affiliation(s)
- Eva Bültmann
- Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
| | - Hans Joachim Mußgnug
- Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Antonia Zapf
- Department of Medical Statistics, University Medical Center, Göttingen, Germany
| | - Hans Hartmann
- Clinic for Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Thomas Nägele
- Department of Diagnostic and Interventional Neuroradiology, Radiological University Hospital, University of Tübingen, Tübingen, Germany
| | - Heinrich Lanfermann
- Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
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Pecheva D, Yushkevich P, Batalle D, Hughes E, Aljabar P, Wurie J, Hajnal JV, Edwards AD, Alexander DC, Counsell SJ, Zhang H. A tract-specific approach to assessing white matter in preterm infants. Neuroimage 2017; 157:675-694. [PMID: 28457976 PMCID: PMC5607355 DOI: 10.1016/j.neuroimage.2017.04.057] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 04/12/2017] [Accepted: 04/25/2017] [Indexed: 11/23/2022] Open
Abstract
Diffusion-weighted imaging (DWI) is becoming an increasingly important tool for studying brain development. DWI analyses relying on manually-drawn regions of interest and tractography using manually-placed waypoints are considered to provide the most accurate characterisation of the underlying brain structure. However, these methods are labour-intensive and become impractical for studies with large cohorts and numerous white matter (WM) tracts. Tract-specific analysis (TSA) is an alternative WM analysis method applicable to large-scale studies that offers potential benefits. TSA produces a skeleton representation of WM tracts and projects the group's diffusion data onto the skeleton for statistical analysis. In this work we evaluate the performance of TSA in analysing preterm infant data against results obtained from native space tractography and tract-based spatial statistics. We evaluate TSA's registration accuracy of WM tracts and assess the agreement between native space data and template space data projected onto WM skeletons, in 12 tracts across 48 preterm neonates. We show that TSA registration provides better WM tract alignment than a previous protocol optimised for neonatal spatial normalisation, and that TSA projects FA values that match well with values derived from native space tractography. We apply TSA for the first time to a preterm neonatal population to study the effects of age at scan on WM tracts around term equivalent age. We demonstrate the effects of age at scan on DTI metrics in commissural, projection and association fibres. We demonstrate the potential of TSA for WM analysis and its suitability for infant studies involving multiple tracts.
Evaluation of tract-specific analysis (TSA) for white matter studies in infants. TSA improves white matter tract alignment over scalar-based registration. TSA closely approximates native space tractography DTI values. The first application of TSA to a neonatal population.
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Affiliation(s)
- Diliana Pecheva
- Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, UK; Department of Computer Science and Centre for Medical Image Computing, University College London, UK
| | - Paul Yushkevich
- Penn Image Computing and Science Laboratory (PISCL), Department of Radiology, University of Pennsylvania, Philadelphia, USA
| | - Dafnis Batalle
- Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, UK
| | - Emer Hughes
- Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, UK
| | - Paul Aljabar
- Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, UK
| | - Julia Wurie
- Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, UK
| | - Joseph V Hajnal
- Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, UK
| | - A David Edwards
- Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, UK
| | - Daniel C Alexander
- Department of Computer Science and Centre for Medical Image Computing, University College London, UK
| | - Serena J Counsell
- Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, UK.
| | - Hui Zhang
- Department of Computer Science and Centre for Medical Image Computing, University College London, UK
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