Imaging the Premature Brain- New Knowledge

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Imaging the Premature Brain- New Knowledge Stein Magnus Aukland Haukeland University Hospital University of Bergen NORWAY

No disclosure

Imaging modalities O Skull X-ray O Computer Tomography O Cerebral Ultrasonography (CUS) O Magnetic Resonance Imaging (MRI)

Purpose of imaging O Emergency O Prognostics

Purpose of imaging O Emergency O «A question of life or death» O Severe injury vs Mild injury O Life support strategy

CUS as an Emergency tool O Utility O Available 24-7 O Quick O User-dependent O Information O Hemorrhage (GMH-IVH) O Malformation O Hypoxic-Ischemic Injury GA 24w. Day 2

MRI as a Emergency tool O Utility O MRI at NICU O MRI compatible incubator O Daytime / weekdays O Time consuming O Lack of experience O Information O Hemorrhage O Anatomy O Signal abnormalities O Restricted diffusion

In the Emergency setting: CUS no 1!

Purpose of imaging OPrognostics To use Imaging as a predictor of outcome

WARNING The practice of routine early neonatal neuroimaging to predict Neurodevelopmental Impairment (NDI) in premature infants is problematic as a plurality of factors influence ultimate neurologic outcomes. Mann P.C, Woodrum D.E, Wilfond B.S, Journal of Pediatrics. 2013 Aug;163(2):587-92.

WARNING We encourage neonatal practitioners to reconsider whether the perceived screening benefits are valid and the prediction of NDI (Neurodevelopmental Impairment) definitive. Mann P.C, Woodrum D.E, Wilfond B.S, Journal of Pediatrics. 2013 Aug;163(2):587-92

Prognosis - Outcome O Motor function? O Cognitive? O Behavioral? O Neuropsychiatric? O Quality of Life?

Prognosis Dilemmas in the Measurement of Developmental Outcomes of Preterm Children Maureen Hack, Division of Neonatology, Rainbow Babies & Children s Hospital, Cleveland, Ohio, USA Journal of Pediatrics 2012 Apr;160(4):537-8

Prognosis & Strategy O GMH IVH Germinal Matrix Hemorrhage- Intraventricular Hemorrhage O DESHI Diffuse Excessive High Signal Intensities (DESHI) O CUS vs. MRI

GMH IVH grading Papile s classification: Grade I: GMH /subependymal hemorrhage Grad II: IVH Grade III: IVH with ventricular dilatation Grade IV: IVH with ventricular dilatation and parenchymal extension Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. Papile LA et al Pediatrics 1978 Apr;92(4):529-34.

GMH IVH- long ago O Grade 1 and 2: no effect on outcome O Grade 3 and 4: major effect on outcome

GMH IVH 10 years ago O Extremely low birth weight infants with grades I-II IVH have poorer neurodevelopmental outcomes at 20 months' corrected age than infants with normal cranial ultrasound Grades I-II intraventricular hemorrhage in extremely low birth weight infants: effects on neurodevelopment. Patra K et al. J Pediatr. 2006 Aug;149(2):169-73.

GMH IVH- Nowadays O Grade I II IVH, even with no documented white matter injury or other late ultrasound abnormalities, is associated with adverse neurodevelopmental outcomes in extremely preterm infants.1 O ELBW infants with bilateral compared to those with unilateral grade IV IVH had worse neurodevelopmental outcomes. Infants with grades I III IVH had similar outcomes whether they had unilateral or bilateral IVH 2 Intraventricular Hemorrhage and Neurodevelopmental Outcomes in Extreme Preterm Infants. Bolisetty S et al Pediatrics. 2014 Jan;133(1):5562. 2 Grade and Laterality of Intraventricular Hemorrhage to Predict 18 22 Month Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants. Merhar SL et al. Acta Paediatr. 2012 April ; 101(4): 414 418. 1

Magnetic Resonance Imaging DESHI O Association between DESHI and outcome??

Magnetic Resonance Imaging DESHI O Although DEHSI may represent disturbances in white matter structure, as illustrated by its relationship to altered ADC and FA values, there is no relationship to short-term neurodevelopment outcome.1 O No association between the presence of diffuse excessive high signal intensities and CP or with infant/toddler development (Bayler scale)2 1 High signal intensity on T2-weighted MR imaging at termequivalent age in preterm infants does not predict 2-year neurodevelopmental outcomes. Kidokoro H et al. AJNR Am J Neuroradiol. 2011 Dec;32(11):2005-10. 2 Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants. Skiöld B et al. J Pediatr. 2012 Apr;160(4):559-566.

Magnetic Resonance Imaging DESHI O Although the incidence of DEHSI was high (75%) in preterm infants at near term-equivalent age MR imaging, DEHSI was not predictive of following adverse outcomes.1 O Preterm children with DEHSI have similar neurodevelopmental outcome to those with normal brain MR2 1 Neurodevelopmental outcomes in preterm infants: comparison of infants with and without diffuse excessive high signal intensity on MR images at near-term-equivalent age. Jeon TY et al. Radiology. 2012 May;263(2):518-26. 2 Neuro-developmental outcome at 18 months in premature infants with diffuse excessive high signal intensity on MR imaging of the brain. Hart A et al. Pediatr Radiol 2011 41:1284 1292.

CUS vs MRI O CUS is a good screening tool to detect serious brain injury resulting in motor handicaps.1 O CUS is more sensitive for recognizing acute intraventricular hemorrhage, perforator stroke and sinovenous thrombosis, but less for small cerebellar haemorrhages2 Limitations of routine neuroimaging in predicting out comes of preterm infants. Whyte HE, Blaser S. Neuroradiology. 2013 Sep;55 Suppl 2:3-11 2 Serial cranial ultrasonography or early MRI for detecting preterm brain injury? Plaisier A et al. Arch Dis Child Fetal Neonatal Ed. 2015 Jul;100(4):F293-300 1

CUS vs MRI O Advanced serial CUS seems highly effective in diagnosing preterm brain injury, but may miss cerebellar abnormalities. O MRI is necessary to accurately predict the outcomes of preterm infants, especially cognitive delays. Serial cranial ultrasonography or early MRI for detecting preterm brain injury? Plaisier A et al. Arch Dis Child Fetal Neonatal Ed. 2015 Jul;100(4):F293-300 Limitations of routine neuroimaging in predicting out comes of preterm infants. Whyte HE, Blaser S. Neuroradiology. 2013 Sep;55 Suppl 2:3-11

CUS vs MRI O MRI is more sensitive than CUS, especially useful in the identification of small intraventricular hemorrhage; cerebellar hemorrhage, punctate lesion in the WM and cerebellum and diffuse, non-cystic WM injury 1 O MRI is superior to CUS for the definition of patterns of both WM and GM maturation and injury and therefore has the potential to provide prognostic information on the neurodevelopmental outcomes of the preterm population2 Neuroimaging of white matter injury, intraventricular and cerebellar hemorrhage. Benders MJ et al. Clin Perinatol. 2014 Mar;41(1):69-82. 2 The role of neuroimaging in predicting neurodevelopmental outcomes of preterm neonates., Kwon SH et al. Clin Perinatol. 2014 Mar;41(1):257-83. 1

CUS vs MRI O Near-term CUS and MRI abnormalities were associated with adverse 18- to 22-month outcomes, independent of early CUS and other factors 1 O Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome 2 O Further research is needed to define the role of MRI in neonatal care 3 1 Neuroimaging and neurodevelopmental outcome in extremely preterm infants. Hintz SR et al. Pediatrics. 2015 Jan;135(1):e32-42 2 Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants. Skiöld B et al. J Pediatr. 2012 Apr;160(4):559-5 3 Magnetic resonance imaging of the brain at term equivalent age in extremely premature neonates: to scan or not to scan? Smyser CD et al J Paediatr Child Health. 2012 Sep;48(9):794-800.

CUS vs MRI O Recent studies have found CUS scanning and MRI abnormalities to be equally predictive of cerebral palsy and early childhood cognitive outcomes in preterm infants 1 O CUS and MRI are complementary modalities 2,3 Dilemmas in the measurement of developmental outcomes of preterm children. Hack M. J Pediatr. 2012 Apr;160(4):537-8. 2 Limitations of routine neuroimaging in predicting out comes of preterm infants. Whyte HE, Blaser S. Neuroradiology. 2013 Sep;55 Suppl 2:3-11. 3 Should early cranial MRI of preterm infants become routine? De Vries LS et al. Arch Dis Child Fetal Neonatal Ed. 2015 Jul;100(4):F284-5 1

Strategies O Serial CUS + CUS at term O Serial CUS + CUS & MRI at term O Serial CUS + early MRI O Serial CUS + early MRI and MRI at term

Conclusion O Bedside CUS is still modality of choice in a emergency setting O MRI at term adds valuable prognostic information but its role has to be better defined

Conclusion O CUS and MRI are complementary modalities O Serial CUS and imaging at term (CUS/MRI) seems like a promising strategy

Advanced MRI O Diffusion-MRI is an effective tool for investigating preterm white matter injury.1 O Diffusion-weighted, diffusion tensor, and susceptibility weighted imaging may improve recognition and prediction of outcome 2 1 Diffusion magnetic resonance imaging in preterm brain injury. Pandit AS, Ball G, Edwards AD, Counsell SJ. Neuroradiology. 2013 Sep;55 Suppl 2:65-95. 2 Neuroimaging of white matter injury, intraventricular and cerebellar hemorrhage. Benders J, Kersbergen KJ, de Vries LS. Clin Perinatol. 2014 Mar;41(1):69-82.

Purpose of imaging O Research O Development of the brain O In utero vs ex- utero development O Influence of treatment and life support in the preterm period