Advanced imaging techniques to study brain development in nutritional interventions

Transcription

1 Advanced imaging techniques to study brain development in nutritional interventions Stéphane V. Sizonenko, MD-PhD, PD Division of Development and Growth Department of Child and Adolescent School of Medicine and University Hospital Geneva, Switzerland

2 Brain imaging and human nutrition: which measures to use in intervention studies? Stéphane V. Sizonenko, Claudio Babiloni, Eveline A. de Bruin, Elizabeth B. Isaacs, Lena S. Jönsson, David O. Kennedy, Marie E. Latulippe, M. Hasan Mohajeri, Judith Moreines, Pietro Pietrini, Kristine B. Walhovd, Robert J. Winwood and John W. Sijben Vol. 110 Supplement No. 1 August 2013 British Journal of Nutrition Magnetic Resonance Imaging (3D-MRI, DTI, MRS, fmri) Electroencephalography and magnetoencephalography Near-IR spectroscopy Positron emission tomography imaging Single-photon emission computerised tomography imaging Commissioned by the ILSI Europe Nutrition and Immunity Task Force

3 Magnetic Resonance imaging Non invasive imaging technique usable in human and animals Can be repeated for longitudinal studies Multimodal tool: structure, function and metabolism Available in most secondary-tertiary hospitals Expensive: imaging but also post-processing Not usable without patient cooperation on patient with magnetic sensitive material or device Possible from birth to 2-3 months during sleep after feeding After 3 months until 5-6 years with training of the child

4 MRI as Imaging Biomarker: Visualization of development, injury, plasticity in the human brain Imaging biomarker: Objective measuments of brain tissue caracteristics Multimodal measurements Indicator of a normal developmental process Indicator of pathogenic process Indicator of response to a therapeutic intervention

5 MRI to visualise brain development Preterm 25 weeks Preterm at term Term newborn 1 year 2 year T1 T2 How to delineate and to quantify the changes?

6 Advanced MRI: Multimodal tool to study brain development and injury MACROSTRUCTURE MICROSTRUCTURE METABOLISM FUNCTION T1-T2, 3D MRI DWI-DTI MRS f-mri

7 Degree of sulcation: Gyrification index Dubois J et al. Cerebral Cortex 2008; 18:

8 POF Cortical sulci identification and development 34.0w medial view lateral view vertex view ventral view CiS CaS SFS IFS precs CS precs postcs POS CS IFS SFS UnS CaF GA 32w 31w 30w 29w 28w 27w OlfS IFS ITS UnS UnS CoS SF STS postcs STS ITS postcs POS precs SFS SF CS CaS CiS CaF POF OlfS POS Medial surface Temporal lobe Parietal lobe Frontal lobe CoS Dubois J et al. Cerebral Cortex 2008; 18:

9 Cortical maturation: twin pregnancy and intrauterin growth restriction Dubois J et al. Brain Aug;131:

10 3D-MRI and tissue segmentation Gui L et al Medical Image Analysis 2012

11 MRI segmentation: Cerebral tissue volume measurements Gui L et al ISBI 2011

12 Abnormal brain development in preterm infants: volumetry at term equivalent Preterm with white matter injury Brain volume: WMI: 400 cc Normal: 478 cc NNT: 476 cc Preterm without white matter injury Term newborn Inder TE et al Ann Neurol 1999;46(5):755

13 Abnormal development of deep grey matter nucleus in preterm infants <27 weeks at term Inder TE et al Pediatrics 2005;115:

14 Change in brain growth between 8 and 12 years in preterm infants Percentage of volume changes of total brain, gray and white matter Ment L et al, Pediatrics, 2009

15 MRI segmentation: Cerebral tissue volume reduction in prematurity Gui L et al ISBI 2011 Volpe, J.J., The Lancet Neurology, (1): p

16 Intrauterine Growth Restriction: brain volumes and neurodevelopment Behavior at term: APIB score Tolsa, C. B., et al. (2004). Pediatr Res 56(1):

17 IUGR and hippocampus growth Voxel-based-morphometry Behavior at term: APIB score Bayley MDI score at 24 months Lodygensky G et al. Pediatr Res (4):

18 Diffusion tensor imaging: anisotropy and microstructure Isotropic diffusion anisotropic diffusion Apparent diffusion coefficient (ADC) measures the overall amount of diffusion of water within the tissue. Fractional Anisotropy (FA) measures the preferential direction of water diffusion within the tissue. Le Bihan D et al J Magn Reson Imaging :

19 DTI: Microstructural changes during development Neill JJ et al, NMR in Biomed 2002;15:

20 DTI: diffusion changes during rat cortical development Sizonenko et al, Cerebral Cortex, 2007; 17:

21 DTI: diffusion changes during rat cortical development Sizonenko et al, Cerebral Cortex, 2007; 17:

22 DTI: diffusion changes during white matter development ADC RA PT and FT PT at Term PT and FT PT at Term PCA (weeks) PCA (weeks) Hüppi PS et al Pediatr Res 44: (1998)

23 DTI: Tractography Method that allows to depict data that are provided by diffusion brain imaging The illustrated fibres represent the lignes of quick diffusion of water in a prefrential direction and represent axonal architecture Network of structural connectivity established from DTI (Prof. P. Hüppi & Elda Fischi, Dr Leila Cammoun and Prof. Jean-Philippe Thiran, EPFL, Lausanne

24 Maturation of white matter tracts DTI and RGB maps Tractography Anisotropy changes during development Dubois J, et al. Cereb Cortex 2009;19(2):

25 Effects of prematurity on maturation of the cortico-spinal tract Term newborn- Preterm at term Diffusion indexes along the corticospinal tract, between the internal capsule (0) and the semi-ovale center (1) J Dubois et al, Cerebral Cortex, 2007

26 Long term alteration of white matter microstructure in preterm infants Anisotropy reduction in white matter tract at 11 years Nagy Z et al Pediatr Res 2003

27 3D-MRI, Segmentation and DTI: Cerebral tractography: estimation of axonal trajectories in the WM. Regions of interest are combined with axonal trajectories: measure of the strenght of the connections between pairs of ROIsc. Result: Structural connectivity network within the brain. structural connectivity Hagmann P, et al. (2008). PLoS Biol 6(7): e159. doi: /journal.pbio

28 Connectivity matrix Huppi et al, unpublished

29 Connectivity matrix: L-R connections Control Preterm IUGR Huppi et al, unpublished

30 1H-MRS and P-MRS: metabolic profile during development Preterm (35 weeks) Term 6 months Adult Rat P4, 9.4T Robertson NJ & Cox IJ (2002) MagneRc resonance spectroscopy of the neonatal brain. In MRI of the Neonatal Brain [MA Rutherford, editor].

31 1 H-MRS: metabolic profile of white matter during early development - [choline] Cell membrane constituent - [NAA] Neuronal marker - [myo-inositol] Glial marker - [tcr] Energy metabolism - [Lac] Metabolic marker Metabolite (mmol): NAA Cr Cho m-ino Lac PT (28-30) (n=8) 2.9 ± ± ± ± ±1.2 PT (31-32) (n=12) 3.6 ± ± ± ± ±0.9 PT (33-35) (n=11) 3.3 ± ± ± ± ±0.6 NNT (38-41) (n=9) 7.2 ± ± ± ± ±0.7 Kreis R et al Magn. Reson. Med. 30, (1993) Hüppi PS et al Pediatr Res 37, (1995) Cady EB et al Magn. Reson. Med. 36, (1996)

32 Functional MRI: BOLD signal Neural activation Neurovascular Coupling Fonctional hyperhemia CBF 0 2 extraction CBV oxyhb / deoxyhb > Signal BOLD fmri

33 Functional MRI: audition activation in term and preterm infants Left All conditions versus resting state Heschl gyrus Adult 3 6 Mother versus noise Superior temporal gyrus From Belin et al, 2000 Nature Huppi et al, unpublished 3 6

34 Functional MRI: audition activation in term and preterm infants Specific activations in preterm versus term newborns All conditions versus resting state R L Mother versus noise Mother versus inverse Precentral gyrus Anterior superior temporal gyrus Superior temporal gyrus (Wernicke area) Huppi et al, unpublished

35 Lactoferrin supplementation in developmental brain injury: Hypoxia-Ischemia in neonatal rats LACTATION P0 Lactoferrin supplementation in dam food (1g/kg/d) P3: HI and T 2 Imaging screening T2-MRI DTI P25 T2MRI / DTI / MRS 1H-MRS % of injured % of cortical MACRO-STRUCTURE Sizonenko et al, unpublished Diffusivity - Anisotropy MICRO-STRUCTURE Neurochemical profile METABOLISM

36 Lactoferrin supplementation in developmental brain injury: Hypoxia-Ischemia in neonatal rats MACRO-STRUCTURE Sizonenko et al, unpublished

37 Lactoferrin supplementation in developmental brain injury: Hypoxia-Ischemia in neonatal rats P3 P25: Color maps P25: T2*W MICRO-STRUCTURE HI-Iso HI-Lf CORTEX EXTERNAL CAPSULE Sizonenko et al, unpublished

38 Lactoferrin supplementation in developmental brain injury: IUGR in rat pups GESTATION & LACTATION G0 Lactoferrin supplementation in dam food (1g/kg/d) METABOLISM W3: DEXAMETHASONE EXPOSURE P7 T2MRI / DTI / MRS Sizonenko et al, in press, Pediatric Research

39 Lactoferrin supplementation in developmental brain injury: IUGR in rat pups MICROSTRUCTURE CORPUS CALLOSUM Control Dex Dex-Lacto Fractional anisotropy Sizonenko et al, in press, Pediatric Research

40 MRI to study the effect of nutrition on brain development and injury Powerful multimodal tool that can delineate brain development and injury It has clearly enhanced our understanding of the altered brain development in preterm and IUGR infants It is clearly correlated to neurodevelopmental difficulties in these infants Translational tool that can be applied to clinical and basic research MRI generates biomarkers of brain changes that could be used in nutritional intervention during in early life Need for nutrition specialists to include such measures in nutritional intervention studies: collaboration

41 Collaborators A. Chatagner P. Larvaron E. Somm G. Lodygensky L. Gui J. Dubois F. Lazeyras P. Hüppi Y. Van de Looij N. Kuntz R. Gruetter B. Wang R. Mansourian F. Raymond M. Faure C. Williams P. Gluckman J. Garbow T. Inder J. Neil

42 Funding Swiss National Fund ELA Fondation Motrice Nestlé Research Centre European Consortium NEOBRAIN, FP6 Biomedical Imaging Centre, EPFL, Lausanne Leenards, Louis Jeantet, Von Meissner, Bonninchi, de Reuter Fundations

43 Thank you for your attention