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Neuropediatrics 2015; 46(05): 344-351
DOI: 10.1055/s-0035-1563533
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Brain Perfusion Is Increased at Term in the White Matter of Very Preterm Newborns and Newborns with Congenital Heart Disease: Does this Reflect Activated Angiogenesis?

Pia Wintermark
1   Department of Pediatrics, McGill University, Montreal, Canada
2   Department of Radiology, Boston Children's Hospital, Boston, United States
,
Mirna Lechpammer
3   Department of Pathology, University of California Davis Medical Center, Sacramento, United States
4   Department of Pathology, Boston Children's Hospital, Boston, United States
5   Department of Neurology, Boston Children's Hospital, Boston, United States
,
Bela Kosaras
5   Department of Neurology, Boston Children's Hospital, Boston, United States
,
Frances E. Jensen
5   Department of Neurology, Boston Children's Hospital, Boston, United States
6   Department of Neurology, University of Pennsylvania, Philadelphia, United States
,
Simon K. Warfield
2   Department of Radiology, Boston Children's Hospital, Boston, United States
› Author Affiliations
Further Information

Publication History

14 April 2015

04 July 2015

Publication Date:
04 September 2015 (online)

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Abstract

Objective This study aims to evaluate brain perfusion at term in very preterm newborns and newborns with congenital heart disease before their corrective surgery, and to search for histopathological indicators of whether the brain perfusion abnormalities of these newborns may be related to an activated angiogenesis.

Materials and Methods Using magnetic resonance imaging and arterial spin labeling, regional cerebral blood flow was measured at a term-equivalent age for three very preterm newborns (born at < 32 weeks), one newborn with congenital heart disease before his corrective surgery and three healthy newborns. In addition, a histopathological analysis was performed on a newborn with congenital heart disease.

Results The very preterm newborns and the newborn with congenital heart disease included in this study all displayed an increased signal in their white matter on T2-weighted imaging. The cerebral blood flow of these newborns was increased in their white matter, compared with the healthy term newborns. The vascular endothelial growth factor was overexpressed in the injured white matter of the newborn with congenital heart disease.

Conclusion Brain perfusion may be increased at term in the white matter, in very preterm newborns, and newborns with congenital heart disease, and it correlates with white matter abnormalities on conventional imaging.

Keywords

angiogenesis - brain perfusion - congenital heart disease - magnetic resonance imaging - premature
 

  • References

  • 1 Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med 2006; 355 (7) 685-694
    CrossrefPubMedGoogle Scholar
  • 2 Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol 2009; 8 (1) 110-124
    CrossrefPubMedGoogle Scholar
  • 3 Back SA, Riddle A, McClure MM. Maturation-dependent vulnerability of perinatal white matter in premature birth. Stroke 2007; 38 (2, Suppl): 724-730
    CrossrefPubMedGoogle Scholar
  • 4 du Plessis AJ. Cerebrovascular injury in premature infants: current understanding and challenges for future prevention. Clin Perinatol 2008; 35 (4) 609-641 , v
    CrossrefPubMedGoogle Scholar
  • 5 Volpe JJ, Kinney HC, Jensen FE, Rosenberg PA. The developing oligodendrocyte: key cellular target in brain injury in the premature infant. Int J Dev Neurosci 2011; 29 (4) 423-440
    CrossrefPubMedGoogle Scholar
  • 6 Goff DA, Buckley EM, Durduran T, Wang J, Licht DJ. Noninvasive cerebral perfusion imaging in high-risk neonates. Semin Perinatol 2010; 34 (1) 46-56
    CrossrefPubMedGoogle Scholar
  • 7 Licht DJ, Shera DM, Clancy RR , et al. Brain maturation is delayed in infants with complex congenital heart defects. J Thorac Cardiovasc Surg 2009; 137 (3) 529-536 , discussion 536–537
    CrossrefPubMedGoogle Scholar
  • 8 Khalil A, Suff N, Thilaganathan B, Hurrell A, Cooper D, Carvalho JS. Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2014; 43 (1) 14-24
    CrossrefPubMedGoogle Scholar
  • 9 Dimitropoulos A, McQuillen PS, Sethi V , et al. Brain injury and development in newborns with critical congenital heart disease. Neurology 2013; 81 (3) 241-248
    CrossrefPubMedGoogle Scholar
  • 10 Martinez-Biarge M, Jowett VC, Cowan FM, Wusthoff CJ. Neurodevelopmental outcome in children with congenital heart disease. Semin Fetal Neonatal Med 2013; 18 (5) 279-285
    CrossrefPubMedGoogle Scholar
  • 11 Miller SP, McQuillen PS, Hamrick S , et al. Abnormal brain development in newborns with congenital heart disease. N Engl J Med 2007; 357 (19) 1928-1938
    CrossrefPubMedGoogle Scholar
  • 12 Owen M, Shevell M, Donofrio M , et al. Brain volume and neurobehavior in newborns with complex congenital heart defects. J Pediatr 2014; 164 (5) 1121-1127.e1
    CrossrefPubMedGoogle Scholar
  • 13 De Vis JB, Hendrikse J, Petersen ET , et al. Arterial spin-labelling perfusion MRI and outcome in neonates with hypoxic-ischemic encephalopathy. Eur Radiol 2015; 25 (1) 113-121
    CrossrefPubMedGoogle Scholar
  • 14 Massaro AN, Bouyssi-Kobar M, Chang T, Vezina LG, du Plessis AJ, Limperopoulos C. Brain perfusion in encephalopathic newborns after therapeutic hypothermia. AJNR Am J Neuroradiol 2013; 34 (8) 1649-1655
    CrossrefPubMedGoogle Scholar
  • 15 Wintermark P, Hansen A, Gregas MC , et al. Brain perfusion in asphyxiated newborns treated with therapeutic hypothermia. AJNR Am J Neuroradiol 2011; 32 (11) 2023-2029
    CrossrefPubMedGoogle Scholar
  • 16 Miranda MJ, Olofsson K, Sidaros K. Noninvasive measurements of regional cerebral perfusion in preterm and term neonates by magnetic resonance arterial spin labeling. Pediatr Res 2006; 60 (3) 359-363
    CrossrefPubMedGoogle Scholar
  • 17 De Vis JB, Petersen ET, de Vries LS , et al. Regional changes in brain perfusion during brain maturation measured non-invasively with Arterial Spin Labeling MRI in neonates. Eur J Radiol 2013; 82 (3) 538-543
    CrossrefPubMedGoogle Scholar
  • 18 Rutherford M, Counsell S, Allsop J , et al. Diffusion-weighted magnetic resonance imaging in term perinatal brain injury: a comparison with site of lesion and time from birth. Pediatrics 2004; 114 (4) 1004-1014
    CrossrefPubMedGoogle Scholar
  • 19 Wintermark P, Moessinger AC, Gudinchet F, Meuli R. Temporal evolution of MR perfusion in neonatal hypoxic-ischemic encephalopathy. J Magn Reson Imaging 2008; 27 (6) 1229-1234
    CrossrefPubMedGoogle Scholar
  • 20 Shaikh H, Lechpammer M, Jensen FE , et al. Increased brain perfusion persists over the first month of life in term asphyxiated newborns treated with hypothermia: Does it reflect activated angiogenesis?. Transl Stroke Res 2015; 6 (3) 224-233
    CrossrefPubMedGoogle Scholar
  • 21 del Zoppo GJ. Stroke and neurovascular protection. N Engl J Med 2006; 354 (6) 553-555
    CrossrefPubMedGoogle Scholar
  • 22 Wintermark P. Injury and repair in perinatal brain injury: Insights from non-invasive MR perfusion imaging. Semin Perinatol 2015; 39 (2) 124-129
    CrossrefPubMedGoogle Scholar
  • 23 Luh WM, Wong EC, Bandettini PA, Hyde JS. QUIPSS II with thin-slice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med 1999; 41 (6) 1246-1254
    CrossrefPubMedGoogle Scholar
  • 24 Cavuşoğlu M, Pfeuffer J, Uğurbil K, Uludağ K. Comparison of pulsed arterial spin labeling encoding schemes and absolute perfusion quantification. Magn Reson Imaging 2009; 27 (8) 1039-1045
    CrossrefPubMedGoogle Scholar
  • 25 Wang J, Licht DJ, Jahng GH , et al. Pediatric perfusion imaging using pulsed arterial spin labeling. J Magn Reson Imaging 2003; 18 (4) 404-413
    CrossrefPubMedGoogle Scholar
  • 26 He L, Parikh NA. Automated detection of white matter signal abnormality using T2 relaxometry: application to brain segmentation on term MRI in very preterm infants. Neuroimage 2013; 64: 328-340
    CrossrefPubMedGoogle Scholar
  • 27 Inder TE, Wells SJ, Mogridge NB, Spencer C, Volpe JJ. Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study. J Pediatr 2003; 143 (2) 171-179
    CrossrefPubMedGoogle Scholar
  • 28 Dyet LE, Kennea N, Counsell SJ , et al. Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment. Pediatrics 2006; 118 (2) 536-548
    CrossrefPubMedGoogle Scholar
  • 29 Jeon TY, Kim JH, Yoo SY , et al. Neurodevelopmental outcomes in preterm infants: comparison of infants with and without diffuse excessive high signal intensity on MR images at near-term-equivalent age. Radiology 2012; 263 (2) 518-526
    CrossrefPubMedGoogle Scholar
  • 30 Fischer I, Gagner JP, Law M, Newcomb EW, Zagzag D. Angiogenesis in gliomas: biology and molecular pathophysiology. Brain Pathol 2005; 15 (4) 297-310
    PubMedGoogle Scholar
  • 31 Noguchi T, Yoshiura T, Hiwatashi A , et al. Perfusion imaging of brain tumors using arterial spin-labeling: correlation with histopathologic vascular density. AJNR Am J Neuroradiol 2008; 29 (4) 688-693
    CrossrefPubMedGoogle Scholar
  • 32 Wintermark P, Lechpammer M, Warfield SK , et al. Perfusion imaging of focal cortical dysplasia using arterial spin labeling: Correlation with histopathological vascular density. J Child Neurol 2013; 28 (11) 1474-1482
    CrossrefPubMedGoogle Scholar
  • 33 Brossard-Racine M, du Plessis AJ, Vezina G , et al. Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease. AJNR Am J Neuroradiol 2014; 35 (8) 1593-1599
    CrossrefPubMedGoogle Scholar
  • 34 Hinton RB, Andelfinger G, Sekar P , et al. Prenatal head growth and white matter injury in hypoplastic left heart syndrome. Pediatr Res 2008; 64 (4) 364-369
    CrossrefPubMedGoogle Scholar
  • 35 Arai Y, Deguchi K, Takashima S. Vascular endothelial growth factor in brains with periventricular leukomalacia. Pediatr Neurol 1998; 19 (1) 45-49
    CrossrefPubMedGoogle Scholar
  • 36 Folkerth RD. The neuropathology of acquired pre- and perinatal brain injuries. Semin Diagn Pathol 2007; 24 (1) 48-57
    CrossrefPubMedGoogle Scholar
  • 37 Pryds O, Greisen G, Lou H, Friis-Hansen B. Vasoparalysis associated with brain damage in asphyxiated term infants. J Pediatr 1990; 117 (1 Pt 1) 119-125
    CrossrefPubMedGoogle Scholar
  • 38 Shi Y, Jin RB, Zhao JN, Tang SF, Li HQ, Li TY. Brain positron emission tomography in preterm and term newborn infants. Early Hum Dev 2009; 85 (7) 429-432
    CrossrefPubMedGoogle Scholar
  • 39 Wintermark P, Moessinger AC, Gudinchet F, Meuli R. Perfusion-weighted magnetic resonance imaging patterns of hypoxic-ischemic encephalopathy in term neonates. J Magn Reson Imaging 2008; 28 (4) 1019-1025
    CrossrefPubMedGoogle Scholar
  • 40 Hartnett ME. Vascular endothelial growth factor antagonist therapy for retinopathy of prematurity. Clin Perinatol 2014; 41 (4) 925-943
    CrossrefPubMedGoogle Scholar