Skip to main content

Advertisement

SpringerLink
Log in

Structural Changes in the Cortico-Ponto-Cerebellar Axis at Birth are Associated with Abnormal Neurological Outcomes in Childhood

  • Original Article
  • Published:
Clinical Neuroradiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Glass HC, Costarino AT, Stayer SA, Brett CM, Cladis F, Davis PJ. Outcomes for extremely premature infants. Anesth Analg. 2015;120:1337–51.

    PubMed  PubMed Central  Google Scholar 

  2. Miller SP, Ferriero DM, Leonard C, Piecuch R, Glidden DV, Partridge JC, Perez M, Mukherjee P, Vigneron DB, Barkovich AJ. Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J Pediatr. 2005;147:609–16.

    PubMed  Google Scholar 

  3. Counsell SJ, Shen Y, Boardman JP, Larkman DJ, Kapellou O, Ward P, Allsop JM, Cowan FM, Hajnal JV, Edwards AD, Rutherford MA. Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age. Pediatrics. 2006;117:376–86.

    PubMed  Google Scholar 

  4. Counsell SJ, Dyet LE, Larkman DJ, Nunes RG, Boardman JP, Allsop JM, Fitzpatrick J, Srinivasan L, Cowan FM, Hajnal JV, Rutherford MA, Edwards AD. Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography. Neuroimage. 2007;34:896–904.

    PubMed  Google Scholar 

  5. Voss W, Neubauer AP, Wachtendorf M, Verhey JF, Kattner E. Neurodevelopmental outcome in extremely low birth weight infants: what is the minimum age for reliable developmental prognosis? Acta Paediatr. 2007;96:342–7.

    PubMed  Google Scholar 

  6. Mathur A, Inder T. Magnetic resonance imaging--insights into brain injury and outcomes in premature infants. J Commun Disord. 2009;42:248–55.

    PubMed  PubMed Central  Google Scholar 

  7. Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol. 2009;8:110–24.

    PubMed  PubMed Central  Google Scholar 

  8. Glass HC, Shellhaas RA, Tsuchida TN, Chang T, Wusthoff CJ, Chu CJ, Cilio MR, Bonifacio SL, Massey SL, Abend NS, Soul JS; Neonatal Seizure Registry study group. Seizures in Preterm Neonates: A Multicenter Observational Cohort Study. Pediatr Neurol. 2017;72:19–24.

    PubMed  PubMed Central  Google Scholar 

  9. Orchinik LJ, Taylor HG, Espy KA, Minich N, Klein N, Sheffield T, Hack M. Cognitive outcomes for extremely preterm/extremely low birth weight children in kindergarten. J Int Neuropsychol Soc. 2011;17:1067–79.

    PubMed  PubMed Central  Google Scholar 

  10. Woodward LJ, Clark CA, Bora S, Inder TE. Neonatal white matter abnormalities an important predictor of neurocognitive outcome for very preterm children. PLoS One. 2012;7:e51879.

    PubMed  PubMed Central  CAS  Google Scholar 

  11. Kwon SH, Vasung L, Ment LR, Huppi PS. The role of neuroimaging in predicting neurodevelopmental outcomes of preterm neonates. Clin Perinatol. 2014;41:257–83.

    PubMed  Google Scholar 

  12. Kostović I, Kostović-Srzentić M, Benjak V, Jovanov-Milošević N, Radoš M. Developmental dynamics of radial vulnerability in the cerebral compartments in preterm infants and neonates. Front Neurol. 2014;5:139.

    PubMed  PubMed Central  Google Scholar 

  13. Miller SP, Ferriero DM. From selective vulnerability to connectivity: insights from newborn brain imaging. Trends Neurosci. 2009;32:496–505.

    PubMed  PubMed Central  CAS  Google Scholar 

  14. Woodward LJ, Edgin JO, Thompson D, Inder TE. Object working memory deficits predicted by early brain injury and development in the preterm infant. Brain. 2005;128:2578–87.

    PubMed  Google Scholar 

  15. Kostović I, Jovanov-Milošević N, Radoš M, Sedmak G, Benjak V, Kostović-Srzentić M, Vasung L, Čuljat M, Radoš M, Hüppi P, Judaš M. Perinatal and early postnatal reorganization of the subplate and related cellular compartments in the human cerebral wall as revealed by histological and MRI approaches. Brain Struct Funct. 2014;219:231–53.

    PubMed  Google Scholar 

  16. Judaš M, Radoš M, Jovanov-Milošević N, Hrabac P, Kostović I. Structural, immunocytochemical, and MR imaging properties of periventricular crossroads of growing cortical pathways in preterm infants. AJNR Am J Neuroradiol. 2005;26:2671–84.

    PubMed  PubMed Central  Google Scholar 

  17. Vasung L, Huang H, Jovanov-Milošević N, Pletikos M, Mori S, Kostović I. Development of axonal pathways in the human fetal fronto-limbic brain: histochemical characterization and diffusion tensor imaging. J Anat. 2010;217:400–17.

    PubMed  PubMed Central  Google Scholar 

  18. Kidokoro H, Neil JJ, Inder TE. New MR imaging assessment tool to define brain abnormalities in very preterm infants at term. AJNR Am J Neuroradiol. 2013;34:2208–14.

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Ment LR, Hirtz D, Hüppi PS. Imaging biomarkers of outcome in the developing preterm brain. Lancet Neurol. 2009;8:1042–55.

    PubMed  Google Scholar 

  20. Volpe JJ. Cerebral white matter injury of the premature infant-more common than you think. Pediatrics. 2003;112:176–80.

    PubMed  Google Scholar 

  21. Chao CP, Zaleski CG, Patton AC. Neonatal hypoxic-ischemic encephalopathy: multimodality imaging findings. Radiographics. 2006;26 Suppl 1:S159–72.

    PubMed  Google Scholar 

  22. Eyre JA, Miller S, Clowry GJ, Conway EA, Watts C. Functional corticospinal projections are established prenatally in the human foetus permitting involvement in the development of spinal motor centres. Brain. 2000;123:51–64.

    PubMed  Google Scholar 

  23. Eyre JA. Development and plasticity of the corticospinal system in man. Neural Plast. 2003;10:93–106.

    PubMed  PubMed Central  CAS  Google Scholar 

  24. Eyre JA. Corticospinal tract development and its plasticity after perinatal injury. Neurosci Biobehav Rev. 2007;31:1136–49.

    PubMed  CAS  Google Scholar 

  25. Schmahmann JD, Pandya DN. Projections to the basis pontis from the superior temporal sulcus and superior temporal region in the rhesus monkey. J Comp Neurol. 1991;308:224–48.

    PubMed  CAS  Google Scholar 

  26. Schmahmann JD, Pandya DN. Prefrontal cortex projections to the basilar pons in rhesus monkey: implications for the cerebellar contribution to higher function. Neurosci Lett. 1995;199:175–8.

    PubMed  CAS  Google Scholar 

  27. Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci. 2003;23:8432–44.

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Schmahmann JD, Rosene DL, Pandya DN. Motor projections to the basis pontis in rhesus monkey. J Comp Neurol. 2004;478:248–68.

    PubMed  Google Scholar 

  29. Ramnani N. The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci. 2006;7:511–22.

    PubMed  CAS  Google Scholar 

  30. Kamali A, Kramer LA, Frye RE, Butler IJ, Hasan KM. Diffusion tensor tractography of the human brain cortico-ponto-cerebellar pathways: a quantitative preliminary study. J Magn Reson Imaging. 2010;32:809–17.

    PubMed  PubMed Central  Google Scholar 

  31. Palesi F, De Rinaldis A, Castellazzi G, Calamante F, Muhlert N, Chard D, Tournier JD, Magenes G, D’Angelo E, Gandini Wheeler-Kingshott CAM. Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas. Sci Rep. 2017;7:12841.

    PubMed  PubMed Central  Google Scholar 

  32. Vasung L, Jovanov-Milošević N, Pletikos M, Mori S, Judaš M, Kostović I. Prominent periventricular fiber system related to ganglionic eminence and striatum in the human fetal cerebrum. Brain Struct Funct. 2011;215:237–53.

    PubMed  CAS  Google Scholar 

  33. Vasung L, Raguz M, Kostovic I, Takahashi E. Spatiotemporal Relationship of Brain Pathways during Human Fetal Development Using High-Angular Resolution Diffusion MR Imaging and Histology. Front Neurosci. 2017;11:348.

    PubMed  PubMed Central  Google Scholar 

  34. Gao W, Lin W, Chen Y, Gerig G, Smith JK, Jewells V, Gilmore JH. Temporal and spatial development of axonal maturation and myelination of white matter in the developing brain. AJNR Am J Neuroradiol. 2009;30:290–6.

    PubMed  PubMed Central  CAS  Google Scholar 

  35. Gousias IS, Edwards AD, Rutherford MA, Counsell SJ, Hajnal JV, Rueckert D, Hammers A. Magnetic resonance imaging of the newborn brain: manual segmentation of labelled atlases in term-born and preterm infants. Neuroimage. 2012;62:1499–509.

    PubMed  Google Scholar 

  36. Kostović Srzentić M, Raguž M, Ozretić D. Specific cognitive deficits in preschool age correlated with qualitative and quantitative MRI parameters in prematurely born children. Pediatr Neonatol. 2020;61:160–7.

    PubMed  Google Scholar 

  37. Katušić A, Raguž M, Žunić Išasegi I. Brain tissue volumes at term-equivalent age are associated with early motor behavior in very preterm infants. Int J Dev Neurosci. 2020; doi: 10.1002/jdn.10039. Epub ahead of print.

    Article  PubMed  Google Scholar 

  38. Inder TE, Warfield SK, Wang H, Hüppi PS, Volpe JJ. Abnormal cerebral structure is present at term in premature infants. Pediatrics. 2005;115:286–94.

    PubMed  Google Scholar 

  39. de Kieviet JF, Zoetebier L, van Elburg RM, Vermeulen RJ, Oosterlaan J. Brain development of very preterm and very low-birthweight children in childhood and adolescence: a meta-analysis. Dev Med Child Neurol. 2012;54:313–23.

    PubMed  Google Scholar 

  40. Peterson BS, Vohr B, Staib LH, Cannistraci CJ, Dolberg A, Schneider KC, Katz KH, Westerveld M, Sparrow S, Anderson AW, Duncan CC, Makuch RW, Gore JC, Ment LR. Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. JAMA. 2000;284:1939–47.

    PubMed  CAS  Google Scholar 

  41. Van Kooij BJ, Benders MJ, Anbeek P, Van Haastert IC, De Vries LS, Groenendaal F. Cerebellar volume and proton magnetic resonance spectroscopy at term, and neurodevelopment at 2 years of age in preterm infants. Dev Med Child Neurol. 2012;54:260–6.

    PubMed  Google Scholar 

  42. Pierson CR, Folkerth RD, Billiards SS, Trachtenberg FL, Drinkwater ME, Volpe JJ, Kinney HC. Gray matter injury associated with periventricular leukomalacia in the premature infant. Acta Neuropathol. 2007;114:619–31.

    PubMed  PubMed Central  Google Scholar 

  43. Limperopoulos C, Chilingaryan G, Guizard N, Robertson RL, Du Plessis AJ. Cerebellar injury in the premature infant is associated with impaired growth of specific cerebral regions. Pediatr Res. 2010;68:145–50.

    PubMed  Google Scholar 

  44. Tam EW, Ferriero DM, Xu D, Berman JI, Vigneron DB, Barkovich AJ, Miller SP. Cerebellar development in the preterm neonate: effect of supratentorial brain injury. Pediatr Res. 2009;66:102–6.

    PubMed  PubMed Central  Google Scholar 

  45. Tam EW, Miller SP, Studholme C, Chau V, Glidden D, Poskitt KJ, Ferriero DM, Barkovich AJ. Differential effects of intraventricular hemorrhage and white matter injury on preterm cerebellar growth. J Pediatr. 2011;158:366–71.

    PubMed  Google Scholar 

  46. Limperopoulos C, Bassan H, Gauvreau K, Robertson RL Jr, Sullivan NR, Benson CB, Avery L, Stewart J, Soul JS, Ringer SA, Volpe JJ, duPlessis AJ. Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors? Pediatrics. 2007;120:584–93.

    PubMed  Google Scholar 

  47. Limperopoulos C, Chilingaryan G, Sullivan N, Guizard N, Robertson RL, du Plessis AJ. Injury to the premature cerebellum: outcome is related to remote cortical development. Cereb Cortex. 2014;24:728–36.

    PubMed  Google Scholar 

  48. Mori S, Crain BJ, Chacko VP, van Zijl PC. Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol. 1999;45:265–9.

    PubMed  CAS  Google Scholar 

  49. Berman JI, Mukherjee P, Partridge SC, Miller SP, Ferriero DM, Barkovich AJ, Vigneron DB, Henry RG. Quantitative diffusion tensor MRI fiber tractography of sensorimotor white matter development in premature infants. Neuroimage. 2005;27:862–71.

    PubMed  Google Scholar 

  50. Mori S, Wakana S, Nagae-Poetscher L, van Zijl PCM. MRI atlas of human white matter. Oxford, Elsevier, 2006.

    Google Scholar 

  51. Hermoye L, Saint-Martin C, Cosnard G, Lee SK, Kim J, Nassogne MC, Menten R, Clapuyt P, Donohue PK, Hua K, Wakana S, Jiang H, van Zijl PC, Mori S. Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood. Neuroimage. 2006;29:493–504.

    PubMed  Google Scholar 

  52. Barkovich AJ, Miller SP, Bartha A, Newton N, Hamrick SE, Mukherjee P, Glenn OA, Xu D, Partridge JC, Ferriero DM, Vigneron DB. MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy. AJNR Am J Neuroradiol. 2006;27:533–47.

    PubMed  PubMed Central  CAS  Google Scholar 

  53. Catani M, Thiebaut de Schotten M. A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex. 2008;44:1105–32.

    PubMed  Google Scholar 

  54. Huang H, Xue R, Zhang J, Ren T, Richards LJ, Yarowsky P, Miller MI, Mori S. Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging. J Neurosci. 2009;29:4263–73.

    PubMed  PubMed Central  CAS  Google Scholar 

  55. Kidokoro H, Anderson PJ, Doyle LW, Neil JJ, Inder TE. High signal intensity on T2-weighted MR imaging at term-equivalent age in preterm infants does not predict 2-year neurodevelopmental outcomes. AJNR Am J Neuroradiol. 2011;32:2005–10.

    PubMed  PubMed Central  CAS  Google Scholar 

  56. Pandit AS, Ball G, Edwards AD, Counsell SJ. Diffusion magnetic resonance imaging in preterm brain injury. Neuroradiology. 2013;55 Suppl 2:65–95.

    PubMed  Google Scholar 

  57. Counsell SJ, Rutherford MA, Cowan FM, Edwards AD. Magnetic resonance imaging of preterm brain injury. Arch Dis Child Fetal Neonatal Ed. 2003;88:F269–74.

    PubMed  PubMed Central  CAS  Google Scholar 

  58. Counsell SJ, Boardman JP. Differential brain growth in the infant born preterm: current knowledge and future developments from brain imaging. Semin Fetal Neonatal Med. 2005;10:403–10.

    PubMed  Google Scholar 

  59. Logitharajah P, Rutherford MA, Cowan FM. Hypoxic-ischemic encephalopathy in preterm infants: antecedent factors, brain imaging, and outcome. Pediatr Res. 2009;66:222–9.

    PubMed  Google Scholar 

  60. Mai J, Majtanik M, Paxinos G. Atlas of the human brain. 4th ed. San Diego: Academic Press, Elsevier; 2015.

    Google Scholar 

  61. Van Hecke W, Emsell L, Sunaert S. Diffusion Tensor Imaging. New York: Springer; 2016.

    Google Scholar 

  62. Amiel-Tison C. Update of the Amiel-Tison neurologic assessment for the term neonate or at 40 weeks corrected age. Pediatr Neurol. 2002;27:196–212.

    PubMed  Google Scholar 

  63. Hempel MS. Neurological development during toddling age in normal children and children at risk of developmental disorders. Early Hum Dev. 1993;34:47–57.

    PubMed  CAS  Google Scholar 

  64. Conover WJ. Practical nonparametric statistics. New York: John Wiley & Sons; 1999.

    Google Scholar 

  65. Žunić Išasegi I, Radoš M, Krsnik Ž, Radoš M, Benjak V, Kostović I. Interactive histogenesis of axonal strata and proliferative zones in the human fetal cerebral wall. Brain Struct Funct. 2018;223:3919–43.

    PubMed  PubMed Central  Google Scholar 

  66. Counsell SJ, Allsop JM, Harrison MC, Larkman DJ, Kennea NL, Kapellou O, Cowan FM, Hajnal JV, Edwards AD, Rutherford MA. Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality. Pediatrics. 2003;112:1–7.

    PubMed  Google Scholar 

  67. Hüppi PS, Murphy B, Maier SE, Zientara GP, Inder TE, Barnes PD, Kikinis R, Jolesz FA, Volpe JJ. Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging. Pediatrics. 2001;107:455–60.

    PubMed  Google Scholar 

  68. Valkama AM, Tolonen EU, Kerttul LI, Pääkkö EL, Vainionpää LK, Koivist ME. Brainstem size and function at term age in relation to later neurosensory disability in high-risk, preterm infants. Acta Paediatr. 2001;90:909–15.

    PubMed  CAS  Google Scholar 

  69. Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K, Smith JK, Hamer RM, Lin W, Gerig G, Gilmore JH. A structural MRI study of human brain development from birth to 2 years. J Neurosci. 2008;28:12176–82.

    PubMed  PubMed Central  CAS  Google Scholar 

  70. Luo L, O’Leary DD. Axon retraction and degeneration in development and disease. Annu Rev Neurosci. 2005;28:127–56.

    PubMed  CAS  Google Scholar 

  71. O’Leary DD, Terashima T. Cortical axons branch to multiple subcortical targets by interstitial axon budding: implications for target recognition and “waiting periods”. Neuron. 1988;1:901–10.

    PubMed  Google Scholar 

  72. Rakic P, Lombroso PJ. Development of the cerebral cortex: I. Forming the cortical structure. J Am Acad Child Adolesc Psychiatry. 1998;37:116–7.

    PubMed  CAS  Google Scholar 

  73. Rakic P. Images in neuroscience. Brain development, VI: radial migration and cortical evolution. Am J Psychiatry. 1998;155:1150–1.

    PubMed  CAS  Google Scholar 

  74. Kostovic I, Zecevic N. Development of the human cerebellar cortex: change in cholinesterase activity during prenatal period. Bulletin de l’Académie Serbe des Sciences et des Arts. Classe des sciences médicales. 1984;87:1–8.

    Google Scholar 

  75. Sidman RL, Rakic P. Neuronal migration, with special reference to developing human brain: a review. Brain Res. 1973;62:1–35.

    PubMed  CAS  Google Scholar 

  76. Ramon Y Cajal S, May MR. Degeneration and regeneration of the nervous system. London: Oxford University Press; 1928.

    Google Scholar 

  77. Smith MC. Histological findings after hemicerebellectomy in man: anterograde, retrograde and transneuronal degeneration. Brain Res. 1975;95:423–42.

    PubMed  CAS  Google Scholar 

  78. Dinkin M. Trans-synaptic Retrograde Degeneration in the Human Visual System: Slow, Silent, and Real. Curr Neurol Neurosci Rep. 2017;17:16.

    PubMed  Google Scholar 

  79. Volpe JJ. Neurology of the newborn. Philadelphia: Saunders; 2001.

    Google Scholar 

  80. Goldman-Rakic PS. Prenatal formation of cortical input and development of cytoarchitectonic compartments in the neostriatum of the rhesus monkey. J Neurosci. 1981;1:721–35.

    PubMed  PubMed Central  CAS  Google Scholar 

  81. Goldman-Rakic PS, Selemon LD, Schwartz ML. Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey. Neuroscience. 1984;12:719–43.

    PubMed  CAS  Google Scholar 

  82. Staudt M. (Re-)organization of the developing human brain following periventricular white matter lesions. Neurosci Biobehav Rev. 2007;31:1150–6.

    PubMed  Google Scholar 

  83. Rakic P. A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci. 1995;18:383–8.

    PubMed  CAS  Google Scholar 

  84. Ribeiro Gomes AR, Olivier E, Killackey HP, Giroud P, Berland M, Knoblauch K, Dehay C, Kennedy H. Refinement of the Primate Corticospinal Pathway During Prenatal Development. Cereb Cortex. 2020;30:656–71.

    PubMed  Google Scholar 

  85. Miller SP, Vigneron DB, Henry RG, Bohland MA, Ceppi-Cozzio C, Hoffman C, Newton N, Partridge JC, Ferriero DM, Barkovich AJ. Serial quantitative diffusion tensor MRI of the premature brain: development in newborns with and without injury. J Magn Reson Imaging. 2002;16:621–32.

    PubMed  Google Scholar 

  86. Beck E. The origin, course and termination of the prefronto-pontine tract in the human brain. Brain. 1950;73:368–91.

    PubMed  CAS  Google Scholar 

  87. Makropoulos A, Counsell SJ, Rueckert D. A review on automatic fetal and neonatal brain MRI segmentation. Neuroimage. 2018;170:231–48.

    PubMed  Google Scholar 

  88. Weisenfeld NI, Warfield SK. Automatic segmentation of newborn brain MRI. Neuroimage. 2009;47:564–72.

    PubMed  Google Scholar 

Download references

Funding

The research was funded by Croatian Science Foundation projects CSF-IP-09-2014-4517, CSF-IP-2013-11-7379, CSF-IP-09-2014-7406 and CSF-DOK-10-2015. This work was supported in part by the “Research Cooperability” Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014–2020 PSZ-2019-02-4710. It was also co-financed by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain”; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, University Hospital Dubrava, University of Zagreb, School of Medicine, Avenija Gojka Suska 6, HR-10000, Zagreb, Croatia

    Marina Raguž

  2. Croatian Institute for Brain Research, Centre of Excellence for Basic, Clinical and Translational Neuroscience, University of Zagreb, School of Medicine, Zagreb, Croatia

    Marina Raguž, Milan Radoš, Mirna Kostović Srzetić, Iris Žunić Išasegi, Mario Vukšić & Ivica Kostović

  3. Department of Anatomy and Clinical Anatomy, University of Zagreb, School of Medicine, Zagreb, Croatia

    Marina Raguž & Nataša Kovačić

  4. Department of Health Psychology, University of Applied Health Sciences, Zagreb, Croatia

    Mirna Kostović Srzetić

  5. Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, School of Medicine, Zagreb, Croatia

    Nataša Kovačić

  6. Clinical Hospital Centre Zagreb, Department of Pediatrics, University of Zagreb, School of Medicine, Zagreb, Croatia

    Vesna Benjak & Tomislav Ćaleta

Authors
  1. Marina Raguž
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milan Radoš
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mirna Kostović Srzetić
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nataša Kovačić
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Iris Žunić Išasegi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vesna Benjak
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomislav Ćaleta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mario Vukšić
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ivica Kostović
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MaR designed the study, conducted volumetric and tractographic analysis, wrote the paper and interpreted the results. MiR designed the study, performed all MRI scans, contributed to data analysis and interpretation. MKS and NK contributed to statistical data analysis and interpretation of results. IZI contributed in volumetric analysis and interpretation of results. VB and TC helped with the clinical part of neurological examination of prematurely born children and with collecting clinical data. MV contributed to data analysis. IK designed the study, wrote the paper, and interpreted the results. All authors approved the submitted version.

Corresponding author

Correspondence to Marina Raguž.

Ethics declarations

Conflict of interest

M. Raguž, M. Radoš, M. Kostović Srzetić, N. Kovačić, I. Žunić Išasegi, V. Benjak, T. Ćaleta, M. Vukšić and I. Kostović declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical standards

This study was carried out in accordance with the recommendations of ethics board of the University of Zagreb, School of Medicine. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board of the University of Zagreb, School of Medicine.

Additional information

Availability of Data and Material

The datasets generated for this study are available on request to the corresponding author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raguž, M., Radoš, M., Kostović Srzetić, M. et al. Structural Changes in the Cortico-Ponto-Cerebellar Axis at Birth are Associated with Abnormal Neurological Outcomes in Childhood. Clin Neuroradiol 31, 1005–1020 (2021). https://doi.org/10.1007/s00062-021-01017-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00062-021-01017-1

Keywords

Search

Navigation