Skip to main content
Log in

Arterial spin-labelling perfusion MRI and outcome in neonates with hypoxic-ischemic encephalopathy

European Radiology Aims and scope Submit manuscript

Abstract

Purpose

Hyperperfusion may be related to outcome in neonates with hypoxic-ischemic encephalopathy (HIE). The purpose of this study was to evaluate whether arterial spin labelling (ASL) perfusion is associated with outcome in neonates with HIE and to compare the predictive value of ASL MRI to known MRI predictive markers.

Methods

Twenty-eight neonates diagnosed with HIE and assessed with MR imaging (conventional MRI, diffusion-weighted MRI, MR spectroscopy [MRS], and ASL MRI) were included. Perfusion in the basal ganglia and thalami was measured. Outcome at 9 or 18 months of age was scored as either adverse (death or cerebral palsy) or favourable.

Results

The median (range) perfusion in the basal ganglia and thalami (BGT) was 63 (28-108) ml/100 g/min in the neonates with adverse outcome and 28 (12-51) ml/100 g/min in the infants with favourable outcome (p < 0.01). The area-under-the-curve was 0.92 for ASL MRI, 0.97 for MRI score, 0.96 for Lac/NAA and 0.92 for ADC in the BGT. The combination of Lac/NAA and ASL MRI results was the best predictor of outcome (r 2 = 0.86, p < 0.001).

Conclusion

Higher ASL perfusion values in neonates with HIE are associated with a worse neurodevelopmental outcome. A combination of the MRS and ASL MRI information is the best predictor of outcome.

Key Points

Arterial spin labelling MRI can predict outcome in neonates with hypoxic-ischemic encephalopathy

Basal ganglia and thalami perfusion is higher in neonates with adverse outcome

Arterial spin labelling complements known MRI parameters in the prediction of outcome

The combined information of ASL and MRS measurements is the best predictor of outcome

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

Access this article

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

Similar content being viewed by others

Abbreviations

ADC:

Apparent diffusion coefficient

aEEG:

Amplitude-integrated electroencephalography

ASL:

Arterial spin labelling

AUC:

Area under the curve

CBF:

Cerebral blood flow

Cho:

Choline

Cr:

Creatine

DWI:

Diffusion-weighted imaging

EPI:

Echo-planar imaging

HIE:

Hypoxic-ischemic encephalopathy

1H MRS:

Proton spectroscopy

ICC:

Intraclass correlation coefficient

Lac:

Lactate

MRI:

Magnetic Resonance Imaging

NAA:

N-acetylaspartate

Pulsar:

Pulsed star labelling of arterial regions

ROI:

Region of interest

SNR:

Signal-to-noise ratio

T1b :

Longitudinal relaxation rate of blood

References

  1. Himmelmann K, Hagberg G, Beckung E, Hagberg B, Uvebrant P (2005) The changing panorama of cerebral palsy in Sweden. IX. Prevalence and origin in the birth-year period 1995-1998. Acta Paediatr 94(3):287–294

    Article  CAS  PubMed  Google Scholar 

  2. Wyatt JS, Gluckman PD, Liu PY et al (2007) Determinants of outcomes after head cooling for neonatal encephalopathy. Pediatrics 119(5):912–921

    Article  PubMed  Google Scholar 

  3. Dilenge ME, Majnemer A, Shevell MI (2001) Long-term developmental outcome of asphyxiated term neonates. J Child Neurol 16(11):781–792

    Article  CAS  PubMed  Google Scholar 

  4. Jouvet P, Cowan FM, Cox P et al (1999) Reproducibility and accuracy of MR imaging of the brain after severe birth asphyxia. AJNR Am J Neuroradiol 20(7):1343–1348

    CAS  PubMed  Google Scholar 

  5. Boichot C, Walker PM, Durand C et al (2006) Term neonate prognoses after perinatal asphyxia: contributions of MR imaging, MR spectroscopy, relaxation times, and apparent diffusion coefficients. Radiology 239(3):839–848

    Article  PubMed  Google Scholar 

  6. Thayyil S, Chandrasekaran M, Taylor A et al (2010) Cerebral magnetic resonance biomarkers in neonatal encephalopathy: a meta-analysis. Pediatrics 125(2):e382–e395

    Article  PubMed  Google Scholar 

  7. Rutherford M, Counsell S, Allsop J et al (2004) Diffusion-weighted magnetic resonance imaging in term perinatal brain injury: a comparison with site of lesion and time from birth. Pediatrics 114(4):1004–1014

    Article  PubMed  Google Scholar 

  8. Pryds O, Greisen G, Lou H, Friis-Hansen B (1990) Vasoparalysis associated with brain damage in asphyxiated term infants. J Pediatr 117(1):119–125

    Article  CAS  PubMed  Google Scholar 

  9. van Bel F, Dorrepaal CA, Benders MJ, Zeeuwe PE, van de Bor M, Berger HM (1993) Changes in cerebral hemodynamics and oxygenation in the first 24 hours after birth asphyxia. Pediatrics 92(3):365–372

    PubMed  Google Scholar 

  10. Rutherford M, Ward P, Allsop J, Malamatentiou C, Counsell S (2005) Magnetic resonance imaging in neonatal encephalopathy. Early Hum Dev 81(1):13–25

    Article  PubMed  Google Scholar 

  11. Grant PE, Yu D (2006) Acute injury to the immature brain with hypoxia with or without hypoperfusion. Magn Reson Imaging Clin N Am 14(2):271–285

    Article  PubMed  Google Scholar 

  12. Meek JH, Elwell CE, McCormick DC et al (1999) Abnormal cerebral haemodynamics in perinatally asphyxiated neonates related to outcome. Arch Dis Child Fetal Neonatal 81(2):110–115

    Article  Google Scholar 

  13. Rosenbaum JL, Almli CR, Yundt KD, Altman DI, Powers WJ (1997) Higher neonatal cerebral blood flow correlates with worse childhood neurologic outcome. Neurology 49(4):1035–1041

    Article  CAS  PubMed  Google Scholar 

  14. Wintermark P, Moessinger AC, Gudinchet F, Meuli R (2008) Temporal evolution of MR perfusion in neonatal hypoxic-ischemic encephalopathy. J Magn Reson Imaging 27(6):1229–1234

    Article  PubMed  Google Scholar 

  15. Blennow M, Ingvar M, Lagercrantz H et al (1995) Early [18 F]FDG positron emission tomography in infants with hypoxic-ischaemic encephalopathy shows hypermetabolism during the postasphyctic period. Acta Paediatr 84(11):1289–1295

    Article  CAS  PubMed  Google Scholar 

  16. Miranda MJ, Olofsson K, Sidaros K (2006) Noninvasive measurements of regional cerebral perfusion in preterm and term neonates by magnetic resonance arterial spin labeling. Pediatr Res 60(3):359–363

    Article  CAS  PubMed  Google Scholar 

  17. Pienaar R, Paldino MJ, Madan N et al (2012) A quantitative method for correlating observations of decreased apparent diffusion coefficient with elevated cerebral blood perfusion in newborns presenting cerebral ischemic insults. Neuroimage 63(3):1510–1518

    Article  PubMed  Google Scholar 

  18. Wintermark P, Warfield S. New Insights in Perinatal Arterial Ischemic Stroke by Assessing Brain Perfusion. Transl Stroke Res 2011; Available at: http://www.springerlink.com (Accessed 10 November 2011)

  19. De Vis JB, Petersen ET, de Vries LS et al (2013) Regional changes in brain perfusion during brain maturation measured non-invasively with Arterial Spin Labeling MRI in neonates. Eur J Radiol 82(3):538–543

    Article  PubMed  Google Scholar 

  20. Petersen ET, Zimine I, Ho Y-CL, Golay X (2006) Non-invasive measurement of perfusion: a critical review of arterial spin labelling techniques. Br J Radiol 79(944):688–701

    Article  CAS  PubMed  Google Scholar 

  21. De Vis JB, Petersen ET, Kersbergen KJ et al (2013) Evaluation of perinatal arterial ischemic stroke using noninvasive arterial spin labeling perfusion MRI. Pediatr Res 74(3):307–313

    Article  PubMed  Google Scholar 

  22. Shi H, Song D, Zhang YX et al (2012) Analysis of arterial spin labeling in 33 patients with hypoxic ischemic encephalopathy. Zhonghua Er Ke Za Zhi 50(2):131–135

    PubMed  Google Scholar 

  23. Wintermark P, Hansen A, Gregas MC et al (2011) Brain perfusion in asphyxiated newborns treated with therapeutic hypothermia. AJNR Am J Neuroradiol 32(11):2023–2029

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Massaro AN, Bouyssi-Kobar M, Chang T, Vezina LG, du Plessis AJ, Limperopoulos C (2013) Brain perfusion in encephalopathic newborns after therapeutic hypothermia. AJNR Am J Neuroradiol 34(8):1649–1655

    Article  CAS  PubMed  Google Scholar 

  25. van Rooij LG, Toet MC, van Huffelen AC et al (2010) Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial. Pediatrics 125(2):e358–e366

    Article  PubMed  Google Scholar 

  26. Lemmers PM, Zwanenburg RJ, Benders MJ et al (2013) Cerebral oxygenation and brain activity after perinatal asphyxia: does hypothermia change their prognostic value? Pediatr Res 74(2):180–185

    Article  CAS  PubMed  Google Scholar 

  27. Shankaran S, Laptook AR, Ehrenkranz RA et al (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353(15):1574–1584

    Article  CAS  PubMed  Google Scholar 

  28. Thompson CM, Puterman AS, Linley LL et al (1997) The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr 86(7):757–761

    Article  CAS  PubMed  Google Scholar 

  29. al Naqeeb N, Edwards AD, Cowan FM, Azzopardi D (1999) Assessment of neonatal encephalopathy by amplitude-integrated electroencephalography. Pediatrics 103(6):1263–1271

    Article  PubMed  Google Scholar 

  30. Golay X, Petersen ET, Hui F (2005) Pulsed star labeling of arterial regions (PULSAR): a robust regional perfusion technique for high field imaging. Magn Reson Med 53(1):15–21

    Article  PubMed  Google Scholar 

  31. Luh WM, Wong EC, Pa B, Hyde JS (1999) 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 41(6):1246–1254

    Article  CAS  PubMed  Google Scholar 

  32. Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR (1998) A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med 40(3):383–396

    Article  CAS  PubMed  Google Scholar 

  33. Varela M, Hajnal JV, Petersen ET, Golay X, Merchant N, Larkman DJ (2011) A method for rapid in vivo measurement of blood T1. NMR Biomed 24(1):80–88

    Article  PubMed  Google Scholar 

  34. de Vries LS, Groenendaal F (2010) Patterns of neonatal hypoxic-ischaemic brain injury. Neuroradiology 52(6):555–566

    Article  PubMed Central  PubMed  Google Scholar 

  35. Roelants-Van Rijn AM, van der Grond J, de Vries LS, Groenendaal F (2001) Value of (1)H-MRS using different echo times in neonates with cerebral hypoxia-ischemia. Pediatr Res 49(3):356–362

    Article  CAS  PubMed  Google Scholar 

  36. Alderliesten T, de Vries LS, Benders MJ, Koopman C, Groenendaal F (2011) MR imaging and outcome of term neonates with perinatal asphyxia: value of diffusion-weighted MR imaging and (1)H MR spectroscopy. Radiology 261(1):235–242

    Article  PubMed  Google Scholar 

  37. Rutherford MA, Pennock JM, Murdoch-Eaton DM, Cowan FM, Dubowitz LM (1992) Athetoid cerebral palsy with cysts in the putamen after hypoxic-ischaemic encephalopathy. Arch Dis Child 67(7):846–850

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Roberts I, Sydenham E (2012) Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev. doi:10.1002/14651858

    Google Scholar 

  39. Kinoshita H, Nakahata K, Dojo M et al (2004) Lidocaine impairs vasodilation mediated by adenosine triphosphate-sensitive K + channels but not by inward rectifier K + channels in rat cerebral microvessels. Anesth Analg 99(3):904–909

    Article  CAS  PubMed  Google Scholar 

  40. de Nadal M, Munar F, Poca MA et al (2000) Cerebral hemodynamic effects of morphine and fentanyl in patients with severe head injury: absence of correlation to cerebral autoregulation. Anesthesiology 92(1):11–19

    Article  PubMed  Google Scholar 

  41. Bingham RM, Hinds CJ (1987) Influence of bolus doses of phenoperidine on intracranial pressure and systemic arterial pressure in traumatic coma. Br J Anaesth 59(5):592–595

    Article  CAS  PubMed  Google Scholar 

  42. Bandres J, Yao L, Nemoto EM et al (1992) Effects of dobutamine and dopamine on whole brain blood flow and metabolism in unanesthetized monkeys. J Neurosurg Anesthesiol 4(4):250–256

    Article  CAS  PubMed  Google Scholar 

  43. Youden WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35

    Article  CAS  PubMed  Google Scholar 

  44. Okereafor A, Allsop J, Counsell SJ et al (2008) Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics 121(5):906–914

    Article  PubMed  Google Scholar 

  45. Wang J, Licht DJ, Jahng G-H et al (2006) Pediatric perfusion imaging using pulsed arterial spin labeling. J Magn Reson Imaging 24(3):249–254

    Article  Google Scholar 

  46. De Vis JB, Hendrikse J, Groenendaal F et al (2014) Impact of neonate haematocrit variability on the longitudinal relaxation time of blood: Implications for arterial spin labelling MRI. Neuroimage Clin 4:517–525

    Article  PubMed Central  PubMed  Google Scholar 

  47. Roche-Labarbe N, Fenoglio A, Aggarwal A et al (2012) Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain. J Cereb Blood Flow Metab 32(3):481–488

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The scientific guarantor of this publication is Jill Britt De Vis. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This study received funding from the Dutch Technology Foundation STW, Applied Science Division of NWO, the technology program of the Ministry of Economic Affairs, and the ZonMw electromagnetic fields and health program. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was waived by the Institutional Review Board. Methodology: prospective diagnostic or prognostic study, performed at one institution.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jill B. De Vis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Vis, J.B., Hendrikse, J., Petersen, E.T. et al. Arterial spin-labelling perfusion MRI and outcome in neonates with hypoxic-ischemic encephalopathy. Eur Radiol 25, 113–121 (2015). https://doi.org/10.1007/s00330-014-3352-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-014-3352-1

Keywords

Navigation