Pediatric Radiology

, Volume 41, Issue 12, pp 1545–1551 | Cite as

Diffuse periventricular leukomalacia in preterm children: assessment of grey matter changes by MRI

  • L. C. Tzarouchi
  • V. Xydis
  • A. K. Zikou
  • A. Drougia
  • L. G. Astrakas
  • M. Papastefanaki
  • S. Andronikou
  • Maria I. ArgyropoulouEmail author
Original Article



Preterm children may have cognitive deficits and behavioural disorders suggestive of grey matter (GM) injury. The prevalence is higher in preterm children with diffuse periventricular leukomalacia (dPVL).


Evaluate changes in the volume of 116 GM areas in preterm children with dPVL.

Methods and materials

Eleven preterm children with dPVL, gestational age 32.8 ± 2.6 weeks, examined at corrected age 22.0 ± 18.2 months and 33 matched preterm controls with normal brain MRI were studied. Volumes of 116 individual GM areas, and white matter/cerebrospinal fluid (WM/CSF) ratio were calculated on T1-weighted high-resolution images after segmentation.


Relative to controls, children with dPVL had decreased GM volume of the hippocampus, amygdala, and frontal lobes and temporal middle gyrus (P  <  0.05); increased GM volume of the putamen, thalamus, globus pallidum, superior temporal gyrus and of the parietal and occipital lobes (P  <  0.05) and lower WM volume/higher CSF volume (P  <  0.05). WM/CSF ratios also differed (P  <  0.05).


Preterm children with dPVL have increased regional GM volume in some areas probably related with a process of brain plasticity-regeneration and reduced GM volume in areas associated with cognition and memory.


MRI Premature birth Periventricular leukomalacia Plasticity 


  1. 1.
    Volpe JJ (2009) Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol 8:110–124PubMedCrossRefGoogle Scholar
  2. 2.
    Blumenthal I (2004) Periventricular leucomalacia: a review. Eur J Pediatr 163:435–442PubMedCrossRefGoogle Scholar
  3. 3.
    Folkerth RD (2006) Periventricular leukomalacia: overview and recent findings. Pediatr Dev Pathol 9:3–13PubMedCrossRefGoogle Scholar
  4. 4.
    Volpe JJ (2003) Cerebral white matter injury of the premature infant-more common than you think. Pediatrics 112:176–180PubMedCrossRefGoogle Scholar
  5. 5.
    Anderson P, Doyle LW (2003) Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s. JAMA 289:3264–3272PubMedCrossRefGoogle Scholar
  6. 6.
    Anderson PJ, Doyle LW (2008) Cognitive and educational deficits in children born extremely preterm. Semin Perinatol 32:51–58PubMedCrossRefGoogle Scholar
  7. 7.
    Hack M, Fanaroff AA (1999) Outcomes of children of extremely low birthweight and gestational age in the 1990’s. Early Hum Dev 53:193–218PubMedCrossRefGoogle Scholar
  8. 8.
    Briscoe J, Gathercole SE, Marlow N (1998) Short-term memory and language outcomes after extreme prematurity at birth. J Speech Lang Hear Res 41:654–666PubMedGoogle Scholar
  9. 9.
    Nosarti C, Giouroukou E, Healy E et al (2008) Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome. Brain 131:205–217PubMedGoogle Scholar
  10. 10.
    Nosarti C, Al-Asady MH, Frangou S et al (2002) Adolescents who were born very preterm have decreased brain volumes. Brain 125:1616–1623PubMedCrossRefGoogle Scholar
  11. 11.
    Peterson BS, Anderson AW, Ehrenkranz R et al (2003) Regional brain volumes and their later neurodevelopmental correlates in term and preterm infants. Pediatrics 111:939–948PubMedCrossRefGoogle Scholar
  12. 12.
    Peterson BS, Vohr B, Staib LH et al (2000) Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. JAMA 284:1939–1947PubMedCrossRefGoogle Scholar
  13. 13.
    Inder TE, Warfield SK, Wang H et al (2005) Abnormal cerebral structure is present at term in premature infants. Pediatrics 115:286–294PubMedCrossRefGoogle Scholar
  14. 14.
    Lin Y, Okumura A, Hayakawa F et al (2001) Quantitative evaluation of thalami and basal ganglia in infants with periventricular leukomalacia. Dev Med Child Neurol 43:481–485PubMedCrossRefGoogle Scholar
  15. 15.
    Tzarouchi LC, Astrakas LG, Zikou A et al (2009) Periventricular leukomalacia in preterm children: assessment of grey and white matter and cerebrospinal fluid changes by MRI. Pediatr Radiol 39:1327–1332PubMedCrossRefGoogle Scholar
  16. 16.
    Alemán-Gómez YM-GL, Valdés-Hernandez P (2006) IBASPM: toolbox for automatic parcellation of brain structures. Twelfth Annual Meeting of the Organization for Human Brain Mapping, Florence, ItalyGoogle Scholar
  17. 17.
    Inder TE, Anderson NJ, Spencer C et al (2003) White matter injury in the premature infant: a comparison between serial cranial sonographic and MR findings at term. AJNR 24:805–809PubMedGoogle Scholar
  18. 18.
    Falip C, Blanc N, Maes E et al (2007) Postnatal clinical and imaging follow-up of infants with prenatal isolated mild ventriculomegaly: a series of 101 cases. Pediatr Radiol 37:981–989PubMedCrossRefGoogle Scholar
  19. 19.
    Altaye M, Holland SK, Wilke M et al (2008) Infant brain probability templates for MRI segmentation and normalization. NeuroImage 43:721–730PubMedCrossRefGoogle Scholar
  20. 20.
    Abernethy LJ, Palaniappan M, Cooke RW (2002) Quantitative magnetic resonance imaging of the brain in survivors of very low birth weight. Arch Dis Child 87:279–283PubMedCrossRefGoogle Scholar
  21. 21.
    Schmidt-Kastner R, Freund TF (1991) Selective vulnerability of the hippocampus in brain ischemia. Neuroscience 40:599–636PubMedCrossRefGoogle Scholar
  22. 22.
    Kuchna I (1994) Quantitative studies of human newborns’ hippocampal pyramidal cells after perinatal hypoxia. Folia Neuropathol 32:9–16PubMedGoogle Scholar
  23. 23.
    Thompson DK, Wood SJ, Doyle LW et al (2008) Neonate hippocampal volumes: prematurity, perinatal predictors, and 2-year outcome. Ann Neurol 63:642–651PubMedCrossRefGoogle Scholar
  24. 24.
    Abraham H, Vincze A, Jewgenow I, et al. Myelination in the human hippocampal formation from midgestation to adulthood. Int J Dev Neurosci 28:401–410Google Scholar
  25. 25.
    Sim FJ, Windrem MS, Goldman SA (2009) Fate determination of adult human glial progenitor cells. Neuron Glia Biol 5:45–55PubMedCrossRefGoogle Scholar
  26. 26.
    Roy NS, Wang S, Harrison-Restelli C et al (1999) Identification, isolation, and promoter-defined separation of mitotic oligodendrocyte progenitor cells from the adult human subcortical white matter. J Neurosci 19:9986–9995PubMedGoogle Scholar
  27. 27.
    Lodygensky GA, Rademaker K, Zimine S et al (2005) Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease. Pediatrics 116:1–7PubMedCrossRefGoogle Scholar
  28. 28.
    Gimenez M, Junque C, Narberhaus A et al (2004) Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity. NeuroImage 23:869–877PubMedCrossRefGoogle Scholar
  29. 29.
    Isaacs EB, Lucas A, Chong WK et al (2000) Hippocampal volume and everyday memory in children of very low birth weight. Pediatr Res 47:713–720PubMedCrossRefGoogle Scholar
  30. 30.
    Beauchamp MH, Thompson DK, Howard K et al (2008) Preterm infant hippocampal volumes correlate with later working memory deficits. Brain 131:2986–2994PubMedCrossRefGoogle Scholar
  31. 31.
    Tzarouchi LC, Astrakas LG, Xydis V et al (2009) Age-related grey matter changes in preterm infants: an MRI study. NeuroImage 47:1148–1153PubMedCrossRefGoogle Scholar
  32. 32.
    Burgel U, Amunts K, Hoemke L et al (2006) White matter fiber tracts of the human brain: three-dimensional mapping at microscopic resolution, topography and intersubject variability. NeuroImage 29:1092–1105PubMedCrossRefGoogle Scholar
  33. 33.
    Bracht T, Tuscher O, Schnell S et al (2009) Extraction of prefronto-amygdalar pathways by combining probability maps. Psychiatry Res 174:217–222PubMedCrossRefGoogle Scholar
  34. 34.
    Heinz A, Braus DF, Smolka MN et al (2005) Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci 8:20–21PubMedCrossRefGoogle Scholar
  35. 35.
    Thierry AM, Gioanni Y, Degenetais E et al (2000) Hippocampo-prefrontal cortex pathway: anatomical and electrophysiological characteristics. Hippocampus 10:411–419PubMedCrossRefGoogle Scholar
  36. 36.
    Nagae LM, Hoon AH Jr, Stashinko E et al (2007) Diffusion tensor imaging in children with periventricular leukomalacia: variability of injuries to white matter tracts. AJNR 28:1213–1222PubMedCrossRefGoogle Scholar
  37. 37.
    Srinivasan L, Dutta R, Counsell SJ et al (2007) Quantification of deep gray matter in preterm infants at term-equivalent age using manual volumetry of 3-tesla magnetic resonance images. Pediatrics 119:759–765PubMedCrossRefGoogle Scholar
  38. 38.
    Ricci D, Anker S, Cowan F et al (2006) Thalamic atrophy in infants with PVL and cerebral visual impairment. Early Hum Dev 82:591–595PubMedCrossRefGoogle Scholar
  39. 39.
    Haynes RL, Xu G, Folkerth RD et al (2011) Potential neuronal repair in cerebral white matter injury in the human neonate. Pediatr Res 69:62–67Google Scholar
  40. 40.
    Okoshi Y, Itoh M, Takashima S (2001) Characteristic neuropathology and plasticity in periventricular leukomalacia. Pediatr Neurol 25:221–226PubMedCrossRefGoogle Scholar
  41. 41.
    Okoshi Y, Mizuguchi M, Itoh M et al (2007) Altered nestin expression in the cerebrum with periventricular leukomalacia. Pediatr Neurol 36:170–174PubMedCrossRefGoogle Scholar
  42. 42.
    Johnston MV (2003) Brain plasticity in paediatric neurology. Eur J Paediatr Neurol 7:105–113PubMedCrossRefGoogle Scholar
  43. 43.
    Staudt M (2007) (Re-)organization of the developing human brain following periventricular white matter lesions. Neurosci Biobehav Rev 31:1150–1156PubMedCrossRefGoogle Scholar
  44. 44.
    Taupin P (2006) Adult neurogenesis and neuroplasticity. Restor Neurol Neurosci 24:9–15PubMedGoogle Scholar
  45. 45.
    Johnston MV (2009) Plasticity in the developing brain: implications for rehabilitation. Dev Disabil Res Rev 15:94–101PubMedCrossRefGoogle Scholar
  46. 46.
    Huttenlocher PR, Dabholkar AS (1997) Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 387:167–178PubMedCrossRefGoogle Scholar
  47. 47.
    Yang Z, Levison SW (2006) Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone. Neuroscience 139:555–564PubMedCrossRefGoogle Scholar
  48. 48.
    Ong J, Plane JM, Parent JM et al (2005) Hypoxic-ischemic injury stimulates subventricular zone proliferation and neurogenesis in the neonatal rat. Pediatr Res 58:600–606PubMedCrossRefGoogle Scholar
  49. 49.
    Felling RJ, Snyder MJ, Romanko MJ et al (2006) Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia. J Neurosci 26:4359–4369PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • L. C. Tzarouchi
    • 1
  • V. Xydis
    • 1
  • A. K. Zikou
    • 1
  • A. Drougia
    • 2
  • L. G. Astrakas
    • 3
  • M. Papastefanaki
    • 1
  • S. Andronikou
    • 2
  • Maria I. Argyropoulou
    • 1
    Email author
  1. 1.Department of Radiology, Medical SchoolUniversity of IoanninaIoanninaGreece
  2. 2.Neonatal Intensive Care Unit, Child Health Department, Medical SchoolUniversity of IoanninaIoanninaGreece
  3. 3.Department of Medical Physics, Medical SchoolUniversity of IoanninaIoanninaGreece

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