Diffuse periventricular leukomalacia Diffuse periventricular leukomalacia in preterm children: Assessment of in preterm children: Assessment of

grey matter changes by MRI grey matter changes by MRI

Tzarouchi LCTzarouchi LC11, Zikou AK, Zikou AK11 ,, Drougia LDrougia L22 , Astrakas LG , Astrakas LG33,, Papastefanaki MPapastefanaki M11, Xydis V, Xydis V11,,

Andronikou SAndronikou S22, Argyropoulou MI, Argyropoulou MI11

1.1. Department of RadiologyDepartment of Radiology2.2. Department Department of Medical Physics of Medical Physics

3.3. Neonatology Clinic - Child Health Neonatology Clinic - Child Health DepartmentDepartment Medical SchoolMedical School, University of Ioannina, University of Ioannina

GREECEGREECE

IntroductionIntroduction

Preterm birth Preterm birth periventricular leukomalaciaperiventricular leukomalacia

Cognition: grey matter developmentCognition: grey matter development

• focalfocal• diffusediffuse

motor deficitsmotor deficits cognitive and behavioral deficitscognitive and behavioral deficits

MRI studies * preterm MRI studies * preterm reduced volumes in grey matter reduced volumes in grey matter

No distinction between focal/diffuse PVLNo distinction between focal/diffuse PVLComparison with full-termComparison with full-term

*Pediatrics 2007;119:759-765Pediatrics 2007;119:759-765*Brain Doi:10.1093/brain/awm282 *Brain Doi:10.1093/brain/awm282 * NeuroImage 2006;32:70-78* NeuroImage 2006;32:70-78*JAMA 2000;284:1939-47*JAMA 2000;284:1939-47

PurposePurpose

To To assess in diffuse PVLassess in diffuse PVL

regional volume of 116 grey matter (GM) areasregional volume of 116 grey matter (GM) areas

Material & Methods IMaterial & Methods I

Study populationStudy population

10 preterm children (9 males and 1 female)10 preterm children (9 males and 1 female)• gestational age 26-36.9, (31.8±2.4 weeks)gestational age 26-36.9, (31.8±2.4 weeks) • corrected age 6.2-70.7 months, (21.78±20.32 corrected age 6.2-70.7 months, (21.78±20.32

months)months) • MRI findings of diffuse PVLMRI findings of diffuse PVL

36 age matched 36 age matched pretermpreterm controls controls

Material & Methods II

1.5 Tesla unit, head coil, 18- 24cm FOV1.5 Tesla unit, head coil, 18- 24cm FOV

• Sagittal SE T1Sagittal SE T1 (TR=(TR=500500ms TE=ms TE=2020msms, , 44mm thick, 0.mm thick, 0.4mm4mm gap gap))

• Axial TSE T2Axial TSE T2 (TR= (TR=35003500ms TE=ms TE=120120msms, 5 mm thick, 0.5, 5 mm thick, 0.5mmmm gap gap))

• Coronal Coronal TSETSE T2 T2 (TR=(TR=35003500ms TE=90, 2.5mm thick, 0mm gap)ms TE=90, 2.5mm thick, 0mm gap)

• 3D spoiled GRE T1 3D spoiled GRE T1 (TR=25ms, TE=4.6ms, 2mm gap)(TR=25ms, TE=4.6ms, 2mm gap)

Data postprocessing IData postprocessing I

NormalizatioNormalizationn

SegmentationSegmentation

MNI templateMNI template

SPM 5.0 + VBM 5.1 toolboxesSPM 5.0 + VBM 5.1 toolboxes

3D T1-WI3D T1-WIforwardforward

Data postprocessing IIData postprocessing IIIndividual grey Individual grey matter maskmatter mask IBASPM atlasIBASPM atlas

Individual AtlasIndividual Atlas

IBASPM toolbox*IBASPM toolbox*

116 GM areas 116 GM areas volume volume

computationcomputation

backward

* * Individual Brain Atlases using Statistical Individual Brain Atlases using Statistical Parametric MappingParametric Mapping

Statistical analysisStatistical analysis

Two tailed Student’s t-testTwo tailed Student’s t-test

P< 0.05 statistically significantP< 0.05 statistically significant

Results Ι Results Ι Frontal Frontal

Superior Superior orbital(cmorbital(cm33

))

Olfactory Olfactory (L/R) (cm(L/R) (cm33))

HippocampHippocampus (L/R)us (L/R)(cm(cm33))

Amygdala Amygdala (L/R)(cm(L/R)(cm33))

MiddleTemporMiddleTemporal Pole al Pole

(L/R) (cm(L/R) (cm33))

PatientsPatients 3.63±0.58 3.63±0.58 1.01±0.211.01±0.21//1.13±0.231.13±0.23

2.2± 2.2± 0.720.72//2.16 2.16

±0.67±0.67

0.81± 0.81± 0.160.16/0.9± /0.9±

0.180.18

1.77 ±0.461.77 ±0.46//2.33 2.33 ±0.75±0.75

ControlsControls 4.15±0.944.15±0.94 1.23±0.311.23±0.31//1.41.4 0.410.41

2.68± 2.68± 0.490.49//2.47± 2.47±

0.440.44

0.95± 0.95± 0.220.22//1.11± 1.11±

0.270.27

2.52 ±0.582.52 ±0.58//2.99 2.99 ±0.61±0.61

PP 0.030.03 <0.001<0.001 0.0030.003 <0.001<0.001 <0.001<0.001

Results ΙResults ΙII

Diffuse PVL > preterm controlsDiffuse PVL > preterm controls

Discussion IDiscussion I GM volume: hippocampusGM volume: hippocampus amygdalaamygdala olfactory gyrusolfactory gyrus frontal superior orbitalfrontal superior orbital middle temporal gyrus middle temporal gyrus

Preterm*: cognitive, behavioral, attention, language, visual-Preterm*: cognitive, behavioral, attention, language, visual- perceptual, learning and working memory deficitsperceptual, learning and working memory deficits

Dorsal limbic pathway

* Dev Med Child Neurol. 2008 Sep;50(9):655-63 Lancet Neurol. 2009 Jan;8(1):110-24

Brain injury Reorganization – Plasticity Brain injury Reorganization – Plasticity

• Axonal sprouting, synaptogenesisAxonal sprouting, synaptogenesis

• Striatum, thalamus, pallidum crossroads of neuronal circuitsStriatum, thalamus, pallidum crossroads of neuronal circuits

• dPVL impairment of myelination, axonal degenerationdPVL impairment of myelination, axonal degeneration axonal sprouting, synaptic prunning axonal sprouting, synaptic prunning

Discussion IIDiscussion II

ConclusionConclusion Diffuse PVL: Diffuse PVL:

• GM atrophy in areas associated with long termGM atrophy in areas associated with long term neurodevelopmental outcomeneurodevelopmental outcome

• Plasticity-reorganization Plasticity-reorganization