Pediatric Radiology

, Volume 41, Issue 10, pp 1284–1292

Neuro-developmental outcome at 18 months in premature infants with diffuse excessive high signal intensity on MR imaging of the brain

  • Anthony Hart
  • Elspeth Whitby
  • Stuart Wilkinson
  • Sathya Alladi
  • Martyn Paley
  • Michael Smith
Original Article



Diffuse excessive high signal intensity (DEHSI) may represent damage to the white matter in preterm infants, but may be best studied alongside quantitative markers. Limited published data exists on its neuro-developmental implications.


The purpose of this study was to assess whether preterm children with DEHSI at term-corrected age have abnormal neuro-developmental outcome.

Materials and methods

This was a prospective observational study of 67 preterm infants with MRI of the brain around term-equivalent age, including diffusion-weighted imaging (DWI). Images were reported as being normal, overtly abnormal or to show DEHSI. A single observer placed six regions of interest in the periventricular white matter and calculated the apparent diffusion coefficients (ADC). DEHSI was defined as (1) high signal on T2-weighted images alone, (2) high signal with raised ADC values or (3) raised ADC values independent of visual appearances. The neuro-development was assessed around 18 months’ corrected age using the Bayley Scales of Infant and Toddler Development (3rd Edition). Standard t tests compared outcome scores between imaging groups.


No statistically significant difference in neuro-developmental outcome scores was seen between participants with normal MRI and DEHSI, regardless of which definition was used.


Preterm children with DEHSI have similar neuro-developmental outcome to those with normal brain MRI, even if the definition includes objective markers alongside visual appearances.


Preterm infants Brain imaging Periventricular leukomalacia Follow-up studies 


  1. 1.
    Wood NS, Marlow N, Costeloe K et al (2000) Neurologic and developmental disability after extremely preterm birth. N Engl J Med 343:378–384PubMedCrossRefGoogle Scholar
  2. 2.
    Marlow N, Wolke D, Bracewell MA et al (2005) Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 352:9–19PubMedCrossRefGoogle Scholar
  3. 3.
    Fily A, Pierrat V, Delporte V et al (2006) Factors associated with neurodevelopmental outcome at 2 years after very preterm birth: the population-based Nord-Pas-de-Calais EPIPAGE cohort. Pediatrics 117:357–366PubMedCrossRefGoogle Scholar
  4. 4.
    Bhutta AT, Cleeves MA, Casey PH et al (2002) Cognitive and behavioral outcomes of school-aged children who were born preterm. JAMA 288:728–737PubMedCrossRefGoogle Scholar
  5. 5.
    Caravale B, Tozzi C, Albino G et al (2005) Cognitive development in low risk preterm infants at 3–4 years of life. Arch Dis Child Fetal Neonatal Ed 90:F474–F479PubMedCrossRefGoogle Scholar
  6. 6.
    Reijneveld SA, de Kleine MJK, van Baar AL et al (2006) Behavioural and emotional problems in very preterm and very low birthweight infants at age 5 years. Arch Dis Child Fetal Neonatal Ed 91:F423–F428PubMedCrossRefGoogle Scholar
  7. 7.
    Woodward LJ, Anderson PJ, Austin NC et al (2006) Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med 355:685–694PubMedCrossRefGoogle Scholar
  8. 8.
    Aida N, Nishimura G, Hachiya Y et al (1998) MR imaging of perinatal brain damage: comparison of clinical outcome with initial and follow-up MR findings. AJNR 19:1909–1921PubMedGoogle Scholar
  9. 9.
    Serdaroglu G, Tekgul H, Kitis O et al (2004) Correlative value of magnetic resonance imaging for neurodevelopmental outcome in periventricular leukomalacia. Dev Med Child Neurol 46:733–739PubMedCrossRefGoogle Scholar
  10. 10.
    Olsen P, Paakko E, Vainionpaa L et al (1997) Magnetic resonance imaging of periventricular leukomalacia and its clinical correlation in children. Ann Neurol 41:754–761PubMedCrossRefGoogle Scholar
  11. 11.
    Hart AR, Whitby EH, Griffiths PD et al (2008) Magnetic resonance imaging and developmental outcome following preterm birth: review of current evidence. Dev Med Child Neurol 50:655–663PubMedCrossRefGoogle Scholar
  12. 12.
    Inder TE, Wells SJ, Mogridge NB et al (2003) Defining the nature of the cerebral abnormalities in the premature infant; a qualitative magnetic resonance imaging study. J Pediatr 143:171–179PubMedCrossRefGoogle Scholar
  13. 13.
    Hamrick SE, Miller SP, Leonard C et al (2004) Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia. J Pediatr 145:593–599PubMedCrossRefGoogle Scholar
  14. 14.
    Volpe JJ (2001) Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res 50:553–562PubMedCrossRefGoogle Scholar
  15. 15.
    Volpe JJ (2003) Cerebral white matter injury of the premature infant-more common than you think. Pediatrics 112:176–180PubMedCrossRefGoogle Scholar
  16. 16.
    Back SA, Riddle A, McClure MM (2007) Maturation dependent vulnerability of perinatal white matter in premature birth. Stroke 38:724–730PubMedCrossRefGoogle Scholar
  17. 17.
    Gilles FH, Gomez IG (2005) Developmental neuropathology of the second half of gestation. Early Hum Dev 81:245–253PubMedCrossRefGoogle Scholar
  18. 18.
    Rutherford MA (2002) MRI of the neonatal brain. W.B.Saunders, LondonGoogle Scholar
  19. 19.
    Maalouf EF, Duggan PJ, Rutherford MA et al (1999) Magnetic resonance imaging of the brain in a cohort of extremely preterm infants. J Pediatr 135:351–357PubMedCrossRefGoogle Scholar
  20. 20.
    Counsell SJ, Allsop JM, Harrison MC et al (2003) Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality. Pediatrics 112:1–7PubMedCrossRefGoogle Scholar
  21. 21.
    Dyet LE, Kennea N, Counsell SJ et al (2006) Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment. Pediatrics 118:536–548PubMedCrossRefGoogle Scholar
  22. 22.
    Counsell SJ, Rutherford MA, Cowan FM et al (2003) Magnetic resonance imaging of preterm brain injury. Arch Dis Child Fetal Neonatal Ed 88:F269–F274PubMedCrossRefGoogle Scholar
  23. 23.
    Counsell SJ, Shen Y, Boardman JP et al (2006) Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age. Pediatrics 117:376–386PubMedCrossRefGoogle Scholar
  24. 24.
    Skiold B, Horsch S, Hallberg B et al (2010) White matter changes in extremely preterm infants, a population-based diffusion tensor imaging study. Acta Paediatr 99:842–849PubMedCrossRefGoogle Scholar
  25. 25.
    Hart AR, Smith MF, Rigby AS et al (2010) Appearances of diffuse excessive high signal intensity (DEHSI) on MR imaging following preterm birth. Pediatr Radiol 40:1390–1396PubMedCrossRefGoogle Scholar
  26. 26.
    Hart AR, Whitby EH, Clark SJ et al (2010) Diffusion-weighted imaging of the cerebral white matter and cerebellum following preterm birth. Dev Med Child Neurol 52:652–659PubMedCrossRefGoogle Scholar
  27. 27.
    Boardman JP, Counsell SJ, Rueckert D et al (2007) Abnormal deep grey matter development following preterm birth detected using deformation-based morphology. Neuroimage 32:70–78CrossRefGoogle Scholar
  28. 28.
    Perneger TV (1998) What's wrong with Bonferroni adjustments? BMJ 316:1236–1238PubMedGoogle Scholar
  29. 29.
    Rigby AS (2010) Statistical recommendations for papers submitted to Developmental Medicine and Child Neurology. Dev Med Child Neurol 52:299–304PubMedCrossRefGoogle Scholar
  30. 30.
    O'Shea TM, Kuban KCK, Allred EN et al (2008) Neonatal cranial ultrasound lesions and developmental delays at 2 years of age among extremely low gestational age children. Pediatrics 122:e662–e669PubMedCrossRefGoogle Scholar
  31. 31.
    Holling EE, Leviton A (1999) Characteristics of cranial ultrasound white-matter echolucencies that predict disability: a review. Dev Med Child Neurol 41:136–139PubMedCrossRefGoogle Scholar
  32. 32.
    de Vries LS, Van Haastert IC, Rademaker KJ et al (2004) Ultrasound abnormalities preceding cerebral palsy in high-risk preterm infants. J Pediatr 144:815–820PubMedGoogle Scholar
  33. 33.
    Miller SP, Cozzio CC, Goldstein RB et al (2003) Comparing the diagnosis of white matter injury in premature newborns with serial MR imaging and transfontanel ultrasonography findings. AJNR 24:1661–1669PubMedGoogle Scholar
  34. 34.
    Maalouf EF, Duggan PJ, Counsell SJ et al (2001) Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants. Pediatrics 107:719–727PubMedCrossRefGoogle Scholar
  35. 35.
    Hagmann CF, De Vita E, Bainbridge A et al (2009) T2 at MR imaging is an objective quantitative measure of cerebral white matter signal intensity abnormality in preterm infants at term-equivalent age. Radiology 252:209–217PubMedCrossRefGoogle Scholar
  36. 36.
    Krishnan ML, Dyet LE, Boardman JP et al (2007) Relationship between white matter apparent diffusion coefficients in preterm infants at term-equivalent age and developmental outcome at 2 years. Pediatrics 120:e604–e609PubMedCrossRefGoogle Scholar
  37. 37.
    Schneider JF, Confort-Gouny S, Le Fur Y et al (2007) Diffusion-weighted imaging in normal fetal brain maturation. Eur Radiol 17:2422–2429PubMedCrossRefGoogle Scholar
  38. 38.
    Huppi PS, Warfield S, Kikinis R et al (1998) Quantitative magnetic resonance imaging of brain development in premature and mature newborns. Ann Neurol 43:224–235PubMedCrossRefGoogle Scholar
  39. 39.
    Hack M, Taylor HG, Drotar D et al (2005) Poor predictive validity of the Bayley Scales of Infant Development for cognitive function of extremely low birth weight children at school age. Pediatrics 116:333–341PubMedCrossRefGoogle Scholar
  40. 40.
    Cornette LG, Tanner SF, Ramenghi LA et al (2002) Magnetic resonance imaging of the infant brain: anatomical characteristics and clinical significance of punctate lesions. Arch Dis Child 86:F171–F177Google Scholar
  41. 41.
    Miller SP, Ferriero DM, Leonard C et al (2005) Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J Pediatr 147:609–616PubMedCrossRefGoogle Scholar
  42. 42.
    Nanba Y, Matsui K, Aida N et al (2007) Magnetic resonance imaging regional T1 abnormalities at term accurately predict motor outcome in preterm infants. Pediatrics 120:e10–e19PubMedCrossRefGoogle Scholar
  43. 43.
    Yung A, Poon G, Qui DQ et al (2007) White matter volume and anisotropy in preterm children: a pilot study of neurocognitive correlates. Pediatr Res 61:732–736PubMedGoogle Scholar
  44. 44.
    Counsell SJ, Edwards AD, Chew ATM et al (2008) Specific relations between neurodevelopmental abilities and white matter microstructure in children born preterm. Brain 131:3201–3208PubMedCrossRefGoogle Scholar
  45. 45.
    Constable RT, Ment LR, Vohr BR et al (2008) Prematurely born children demonstrate white matter microstructural differences at 12 years of age, relative to term control subjects: an investigation of group and gender effects. Pediatrics 121:306–316PubMedCrossRefGoogle Scholar
  46. 46.
    Andrews JS, Ben-Shachar M, Yeatman JD et al (2010) Reading performance correlates with white-matter properties in preterm and term children. Dev Med Child Neurol 52:e94–e100PubMedCrossRefGoogle Scholar
  47. 47.
    Arzoumanian Y, Mirmiran M, Barnes PD et al (2003) Diffusion tensor brain imaging findings at term-equivalent age may predict neurologic abnormalities in low birth weight preterm infants. AJNR 24:1646–1653PubMedGoogle Scholar
  48. 48.
    Son SM, Park SH, Moon HK et al (2009) Diffusion tensor tractography can predict hemiparesis in infants with high risk factors. Neurosci Lett 451:94–97PubMedCrossRefGoogle Scholar
  49. 49.
    Rose J, Mirmiran M, Butler EE et al (2007) Neonatal microstructural development of the internal capsule on diffusion tensor imaging correlates with severity of gait and motor deficits. Dev Med Child Neurol 49:745–750PubMedCrossRefGoogle Scholar
  50. 50.
    Rose J, Butler EE, Lamont LE et al (2009) Neonatal brain structure on MRI and diffusion tensor imaging, sex and neurodevelopment in very-low-birthweight preterm children. Dev Med Child Neurol 51:526–535PubMedCrossRefGoogle Scholar
  51. 51.
    Berman JI, Mukherjee P, Partridge JC et al (2005) Quantitative diffusion tensor MRI fiber tractography of sensorimotor white matter development in premature infants. Neuroimage 27:862–871PubMedCrossRefGoogle Scholar
  52. 52.
    Partridge JC, Mukherjee P, Berman JI et al (2005) Tractography-based quantitation of diffusion tensor imaging parameters in white matter tracts of preterm newborns. J Magn Reson Imaging 22:467–474PubMedCrossRefGoogle Scholar
  53. 53.
    Murakami A, Morimoto M, Yamada K et al (2008) Fiber-tracking techniques can predict the degree of neurologic impairment for periventricular leukomalacia. Pediatrics 122:500–506PubMedCrossRefGoogle Scholar
  54. 54.
    Bassi L, Ricci D, Volzone A et al (2008) Probabilistic diffusion tractography of the optic radiations and visual function in preterm infants at term equivalent age. Brain 131:573–582PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Anthony Hart
    • 1
    • 2
  • Elspeth Whitby
    • 2
  • Stuart Wilkinson
    • 1
  • Sathya Alladi
    • 3
  • Martyn Paley
    • 2
  • Michael Smith
    • 1
  1. 1.Department of NeonatologySheffield Teaching Hospitals NHS Foundation TrustSheffieldUK
  2. 2.Department of Academic RadiologyUniversity of SheffieldSheffieldUK
  3. 3.Department of Child DevelopmentSheffield Teaching Hospitals NHS Foundation TrustSheffieldUK

Personalised recommendations