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Predicting outcome using neonatal MRI
in preterm infantsManon Benders, neonatologist
Summer Conference on Neonatology in Provence
Avignon, France, 6th - 9th September 2017
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the human brain
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30 wks MRI
the third trimester is important for brain development
In utero
Ex utero
40 wks MRI
Affected Neurodevelopment
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Longterm outcome of very preterm infants
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
UK Zweden UK Zweden
Ou
tco
me
(%
)
24 wks 25 wks
Outcome EPICURE-II en EXPRESSof NICU admissions
mild/no abn
moderate/severe
died
• Who is at risk?
• How can we identify those infants?
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• Who is at risk?
• How can we identify those infants?
• Reasons:
• Prediction and information to the parents
• Selection for early neuroprotective intervention
B. Larroque et al, Lancet 2008
5 yrs
decreased IQ
Longterm consequences of prematurity
MRI ?
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• MRI and predicting neuro-motor outcome
• MRI and adverse neurodevelopmental outcome
– White matter injury
– Cerebellar injury
• MRI and quantitative analysis and prediction
Predicting outcome using neonatal MRI
in preterm infants
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Conventional MRI: Prediction of motor outcome
Peri-ventricular hemorrhagic infarction:Evaluation of myelin in the PLIC – T1
NO PLIC
Girl, GA 28+5 wks, IVH gr IV, > hemiplegia - cerebral palsy
De Vries LS, et al , Neuropediatrics 1999De Vries LS, et al. Eur J of Pediatr Neuro 2001
T2 T2 T130wks TEA TEA
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Decreasing Incidence and Severity of CP
van Haastert I. et al. J of Pediatr 2011
N=3287, GA <34 wks1990-2005
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Who is performing routine MRI in preterm infants?
Decrease of CP, however 50% abnormal development> Does routine MRI help to predict outcome?
B. Larroque et al, Lancet 2008
All babies<28 wks
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• MRI and predicting neuro-motor outcome
• MRI and adverse neurodevelopment outcome
– White matter injury
– Cerebellar injury
• MRI and quantitative analysis and prediction
Predicting outcome using neonatal MRI
in preterm infants
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Conventional neuroimaging in the preterm infant:
more subtle lesions – adverse cognitive outcome
M. Hinojosa-Rodríguez et al. NeuroImage: Clinical 16 (2017) 355–368
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• Very preterm infants with low-grade GMH-IVH (n=69)
on cUS have a similar early neurodevelopmental
outcome compared with controls (n=96)
• However, several infants developed neurodevelopmental
impairment
• Additional MRI showed subtle abnormalities that were
missed with cUS, this partly explained CP
Pauline Reubsaet et al, Neonatology 2017
The Impact of Low-Grade IVH on Neurodevelopmental Outcome
of Very Preterm Infants
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The Impact of Low-Grade IVH on Neurodevelopmental Outcome
of Very Preterm Infantsadditional injury on MRI
Pauline Reubsaet et al, Neonatology 2017
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Omizzolo et al. Memory. 2015
Neonatal Brain Abnormalities and Memory and LearningOutcomes at 7 Years in Children Born Very Preterm
n=198 preterm infants vs n=70 term
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• MRI and predicting neuro-motor outcome
• MRI and adverse neurodevelopmental outcome
– White matter injury
– Cerebellar injury
• MRI and quantitative analysis and prediction
Predicting outcome using neonatal MRI
in preterm infants
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White matter injury
Compare to CUS: MRI is more sensitive for detecting
punctate white matter lesions
de Vries, L. S., Benders, M. J. N. L., Groenendaal, F. (2013) Neuroradiology
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Identifying PWML– preterm infantsSusceptibility weighted imaging (SWI)
• Clearly detection of hemorrhagic lesions
• More hemorrhagiclesions were identifiedusing SWI than T2
T1
SWIT2
SWI
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Identifying PWML– preterm infantsDiffusion weighted imaging (DWI)
Hypoxic-ischemic detection of lesions= very clear on DWI and T1/IR
DWICUS IR/T1
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Punctate white matter lesions
Kersbergen PLoS One 2014
112 preterminfants, 2 MRIs
linear patternwith low SI on SWI (n=67)
cluster patternwith high SI on
DWI (n=26)
mixed pattern(n=19)
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PWML n=112
TEA scan: 70%Linear pattern
TEA scan: 12%Cluster pattern
TEA scan: 18%mixed
More florid on T2Often associated withadditional lesions/IVH
More florid on T1 mixed
SWI low signal intensity
DWI restricted diffusion
Follow-up data were available for 91 infants:• 9 infants developed cerebral palsy in cluster group
• 6 with additional lesions• 3 with ‘only’ PWML in the cortical spinal tracts
Kersbergen PLoS One 2014
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Presence of any punctate white matter lesion in corticospinal tracts
GMFCS 2-5 Motor compositescore <85
Odds Ratio
7.859 (2.56–24.17)
2.192 (1.12–4.31)
AUC 0.728 (0.6-0.9)
0.574 (0.5-0.7)
Tusor N, Benders et al. 2017 submitted
Consequence of white matter injury: PWML
Location is important
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Quantitative assessment of white matter
injury in preterm neonates: Association with outcomes
Guo, et al. Neurology 2017
Location motor cognition language
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• MRI and predicting neuro-motor outcome
• MRI and adverse neurodevelopmental outcome
– White matter injury
– Cerebellar injury
• MRI and quantitative analysis and prediction
Predicting outcome using neonatal MRI
in preterm infants
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Preterm girl of 27+3 wks of GA.
1st wk of life 3st wk of life 30wk corrected age
CUS term equivalent age MRI term equivalent age
Unilateral lesion
Compare to CUS: MRI is more sensitive for detecting cerebellar hemorrhages
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Baby boy, GA 27 wks
Bilateral lesion
term equivalent age
30wk corrected age30wk corrected age
1st wk of life 1st wk of life
MASTOID window
CUS CUS
T1 MRI T2 MRI T2 MRI
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CB hemorrhage: cerebello-cerebral diaschisis> altered trophic trans-synaptic interactions
Limperopoulous et al, cerebral cortex 2012
• isolated CB injury
• n = 40
• at 34 mnd MRI and FU
Conclusions:• isolated CB injury is related with secondary impairment of
regional volumetric growth in the contralateral cerebral cortex• remote regional impairments of cerebral volumetric growth
due CB injury related to domain-specific functional deficits
VolpeLimperopoulous et al, Pediatrics 2005, cerebral cortex 2012
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• MRI and predicting neuro-motor outcome
• MRI and adverse neurodevelopmental outcome
– White matter injury
– Cerebellar injury
• MRI and quantitative analysis and prediction
Predicting outcome using neonatal MRI
in preterm infants
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brain development in preterm period
remote injury – white matter injury
Volpe Lancet Neurol 2009
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Cortical folding – sulcus level and prediction of
outcome
Kersbergen K, et al, J of Pediatr 2017
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brain volumes and neurodevelopment
Keunen et al J Pediatr 2016, Anbeek et al PLoS One 2013
neonatal 2 years 5.5 years
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Neonatal network is related to performance IQ at
early school age
Effect size is resp 25% and 27%
Keunen et al, DMCN 2017
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Prediction of cognitive and motor outcome of preterm
infants based on automatic quantitative descriptors
from neonatal MR brain images
Prems <28 wksN=71 serial scans2 yrs Bayley outcome
Moeskops P, et al, scientific report 2017
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Prediction of cognitive and motor outcome of preterm
infants based on automatic quantitative descriptors
from neonatal MR brain images: 2 yrs of age
Moeskops P, et al, submitted
Cognitive score30 wks
Motor score30 wks
40 wks lower AUC
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Machine learning – for diagnosis and prognosis
> individualized care
• Selection for intervention trial?
Parikh Na, Seminars of perinatology 2016
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Why would we like to perform an MRI in
preterm infants?
• To detect brain injury
• To assist in the prediction of high-risk children
• Early neuroprotective intervention?
Why would we like to perform an early MRI in preterm infants?
XVI Update in Neonatologia – Florence
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Erytropoietine
n=24 vs n=34
n=77 vs n=88
Frac
tio
nal
anis
otr
op
y
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• GA 28-33 wks
• Intervention: 1st 72h until 2 wks CA
• Outcome: ABIP and Prechtl (2 wks – 9mnths CA)
electrophysiology (2 wks CA)
MRI (2 wks CA)
Bayley II (24 mths)
Als, H.et al (2004). Pediatrics
Early brain activity relates to subsequent brain development
NIDCAP alters Brain Structure and Function
Higher relative anisotropy in left internal capsulewith a trend for right internal
capsule and frontal white matter
intervention
No intervention
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• n=10, GA 30-33wks
• day 10
• 3 times/day
• two blocks of 5 d
• separated by a 2 d
- higher levels of blood IGF-1
-
- accelerates the maturation of brain activity
Massage Accelerates Brain Development and
the Maturation of Visual Function Early brain activity relates to subsequent brain development
Shortening in IBI Shortening VEP
Guzzetta A et al. J Neurosci 2009,
DMCN 2011
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Conclusion
predicting outcome from MRI in preterm infants
• MRI predicts neurodevelopmental outcome
– More sensitive for smaller/additional lesions – related to outcome
• White matter injury
• Cerebellar injury
– Useful to use quantify brain parameters
• Prediction of neurodevelopmental outcome
– Selection for intervention?
– Evaluation of clinical intervention trials?
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Veel dank Thank youNICU, especially:• Prof. Linda de Vries• Floris Groenendaal• Dr. Niek van der Aa• Dr. Elise Roze
PhD - / medical students• Kristin Keunen• Nienke Wagenaar• Nathalie Claessens• Lisanne Stolwijk• Erik van Tilborg• Elise Turk• Kim Annink
Image science institute:• Prof. Max Viergever• Alexander Leemans• Ivana Isgum• Pim Moeskops
MRI technicians
International collaborators:LONDON:• Prof. Serena CounsellPARIS: • Jessica Dubois
Physiotherapist• Ingelot van Haastert
Physician assistents
RMI / psychiatry• Martijn van de Heuvel
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Questions?