Hot Topics 2009

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  • MRI = Excellent soft tissue contrast of macroscopic anatomy of the brain, but conventional MRI may not always demonstrate microstructural development and disease processes. DTI is a MR technique that provides a quantitative measure of water diffusion in tissue. DTI has the potential to reveal subtle white matter abnormalities that are not demonstrated on conventional MRI and so may be useful in investigating white matter development and pathology in the preterm brain. DTI is essentially similar to DWI, but more directions of diffusion sensitization are measured to enable anisotropy to be calculated more accurately than the three directions used in DW imaging.
  • 1. 70% of all genes are expressed in the brain. 2. To assay brain connectivity in both structural and functional level, has unique potential as a tool for characterising functional genetics in neural circuitry. 3. Imaging genetics typically involves first identifying a meaningful variation in the DNA sequence, such as the William Syndrome,
  • The image on th eleft is from the paper by Behrens et al. and shows thalamo-cortical projections in the adult. Colours are different, but here purple represents fronto-temporal, orange = motor, blue = somatosensory and yellow = parieto/occipital cortex. The central image is of an infant with no abnormality on MRI and is broadly similar to the adult. The image on the right is the infant with lesions. Connections appear diminished, more so on the ipsilateral side to the porencephalic cyst. Could not visualise connections from the sensory cortex on the side. The frontal/temporal cortex appears to connect to the region of the mediodorsal nucleus, the occipital/parietal cortex projects to the region of the pulvinar. Connections from the motor region project to the ventrolateral nuclei and those from the somatosensory region connect to the ventral posterior nucleus.
  • Hot Topics 2009

    1. 1. Brain MRI as a predictor of the future David Edwards © Imperial College London Page
    2. 2. Normal Severe injury T1 weighted images
    3. 3. Distribution of probability that MRI examination of the posterior limb of the internal capsule will correctly assign neurodevelopmental prognosis after neonatal encephalopathy Predictive probability = 94% (95% CI 89-99%) (  density curve: Rutherford et al Pediatrics 1998;102:323-328)
    4. 4. Diffusion weighted image (Cowan et al Neuropediatrics 1994;25:172-175)
    5. 5. 24 weeks gestation Term (Battin et al Lancet 1997;349:1741)
    6. 7. The commonest ‘lesion’ in preterm infants at term: Diffuse Excessive High Signal Intensity on T2 weighted images (DEHSI) (Maalouf et al J Pediatr 1999;135:351) DEHSI
    7. 8. © Imperial College London Page Frequency of abnormalities in MR image of preterm infants at term (Maalouf et al J Pediatr 1999;135:351)
    8. 9. Prediction of cerebral palsy aged 2 1 2 3 Focal lesions White Matter abnormal Ventricles dilated Sensitivity Specificity Cranial Ultrasound Moderate/ Severe White Matter Any White Matter MRI 4
    9. 10. Brain growth in an individual infant © Imperial College London Page Kapellou et al PLOS Medicine 2006; 3:8 .
    10. 11. Reduced cortical growth from 23 to 48 weeks gestational age is related to neurological outcome at 6 years of age © Imperial College London Page
    11. 12. Cortical growth 34 weeks to 40 weeks 29 weeks to 34 weeks
    12. 13. © Imperial College London Page a b c d An Automatic Brain Atlas for infants and children Registered to an MR image defines 83 brain regions automatically Gousias et al NeuroImage 2008:672-684
    13. 14. © Imperial College London Page Thalamic volume is reduced in preterm infants with focal brain lesions Srinivasan et al Pediatrics 2007
    14. 15. Diffusion Tensor Imaging (DTI) © Imperial College London Page
    15. 16. Diffusion Tensor Imaging (DTI) © Imperial College London Page
    16. 17. Tractography © Imperial College London Page Behrens T. E. J., Nature Neuroscience (2003) 6(7), 750-757
    17. 18. Diffusion Tensor Imaging with probabalistic MR tractography © Imperial College London Page Behrens et al Nat Neurosci . 2003 Jul;6(7):750-7 Counsell et al NeuroImage . 2007 Feb 1;34(3):896-904.
    18. 19. © Imperial College London Page <ul><li>Preterm infants at term corrected age: </li></ul><ul><li>Optic tracts defined by tractography for local FA analysis </li></ul><ul><li>TBSS survey showing regions linear relation between FA and visual score </li></ul>a b
    19. 20. © Imperial College London Page -4 -2 0 2 4 e( Visual Score | X ) -.02 -.01 0 .01 .02 .03 e( Fractional Anisotropy | X ) -4 -2 0 2 4 e( Visual Score | X ) -.5 0 .5 1 e( MRI-detected Brain Lesions | X ) -3 -2 -1 0 1 2 e( Visual Score | X ) -2 -1 0 1 2 e( Post-menstrual age at Scan | X ) -3 -2 -1 0 1 2 e( Visual Score | X ) -4 -2 0 2 4 e( Gestational Age at Birth | X ) Bassi et al Brain . 2008 Feb;131(Pt 2):573-82.
    20. 21. Page Preterm infants aged 2 years: regions where FA shows linear correlation to eye-hand co-ordination score
    21. 22. © Imperial College London Page 26 weeks 40 weeks Robinson et al, submittted Thalamus Primary sensory cortex Primary motor cortex
    22. 23. © Imperial College London Page Robinson et al, submittted 26 weeks 40 weeks
    23. 24. Mapping the Thalamus using Diffusion Tractography © Imperial College London Page = frontal/temporal cortex = occipital/parietal cortex = motor neighbourhood = somatosensory area KEY normal White matter lesion Counsell et al NeuroImage . 2007 Feb 1;34(3):896-904.
    24. 26. Insulae to Lingula Superior frontal to medial orbital Superior frontal to anterior orbital Brain regions where connections are strongest in young adults Robinson et al, in progress Caudate to Substantia Nigra Postcentral to Superior Frontal
    25. 27. Thalamus to thalamus Posterior cingulate to pallidum Brain regions where connections are strongest in older adults Robinson et al, in progress Thalamus to putamen Thalamus to insula
    26. 28. © Imperial College London Page Fixation Cross fMRI; brain activation during visual stimulation
    27. 29. © Imperial College London Page Imaging brain activity in a preterm infant by fMRI Rifat et al, EHD 2005 Brain activated by visual stimulation
    28. 30. © Imperial College London Page Somatosensory fMRI in a 29 week infant Arichi et al, in progress
    29. 31. © Imperial College London Page White matter tracts starting from the most activated voxel in fMRI study confirm correct anatomical connections of activate regions Preterm Preterm at term
    30. 32. Background cerebral activity Beckmann et al PNAS 2005 <ul><li>Unstimulated changes in BOLD signal </li></ul><ul><li>Resting State Networks </li></ul>
    31. 33. Term (median 40.5 weeks)
    32. 34. Growth of the cerebral motor system from 29 to 44 weeks gestational age © Imperial College London Page
    33. 35. Growth of the default mode and motor networks from 29 to 44 weeks gestational age © Imperial College London Page
    34. 36. Future uses of MRI in Neonatal Medicine <ul><li>Diagnose serious brain pathology </li></ul><ul><li>Assign prognosis </li></ul><ul><li>Understand brain growth and development </li></ul><ul><li>Investigate brain function </li></ul><ul><li>In clinical trials of neuroprotectants </li></ul>
    35. 37. Recognition <ul><li>Serena Counsell </li></ul><ul><li>Daniel Rueckert </li></ul><ul><li>Jo Hajnal </li></ul><ul><li>James Boardman </li></ul><ul><li>Paul Aljabar </li></ul><ul><li>Kanwal Bhatia </li></ul><ul><li>Mustapha Anjari </li></ul><ul><li>Emma Robinson </li></ul><ul><li>Latha Srinivasan </li></ul><ul><li>Valentina Doria </li></ul><ul><li>Tuula Kaukola </li></ul><ul><li>Emma Robinson </li></ul><ul><li>Laura Bassi </li></ul><ul><li>Christian Beckmann </li></ul><ul><li>Geraint Rees </li></ul><ul><li>Michaela Groppo </li></ul><ul><li>Tom Arichi </li></ul><ul><li>Gareth Ball </li></ul><ul><li>Mary Rutherford </li></ul><ul><li>Frances Cowan </li></ul><ul><li>Joanna Allsop </li></ul><ul><li>Olga Kapellou </li></ul><ul><li>Maria Murgusova </li></ul>© Imperial College London Page
    36. 38. References <ul><li>Ancel P.Y, Livinec F., Larroque B, Marret S, Arnaud C, Pierrat V, Dehan M, N'Guyen S, Escande B, Burguet A, Thiriez G, Picaud J-C, André M, Bréart G, Kaminski M and the EPIPAGE Study Group. Cerebral palsy among very preterm children in relation to gestational age and neonatal ultrasound abnormalities: The EPIPAGE Cohort Study. Paediatrics, 2006; 117: 828-835 </li></ul><ul><li>de Vries L. S. , Inge-Lot C, Van Haastert PPT, MA, Karin J. Radermaker K.J, Koopman C and Groenendaal F. Ultrasound abnormalities preceeding cerebral palsy in high risk preterm infants. Journal of Pediatrics, 2004; 144: 815-20 </li></ul><ul><li>O’Shea MT, Kuban CK, Allred NE, Paneth N, Pagano M, Dammann O, Bostic L Brooklier K, McQuiston S, Miller A, Pasternak S, Plesha-Troyke S, Price J, Romano E, Solomon K.M, Jacobson A, Westra S, Leviton A and for the Extremely Low Gestational Age Newborns Study Investigators. Neonatal cranial ultrasound lesions and developmental delays at 2 years of age among extremely low gestational age children. Pediatrics, 2008; 122: 662-66916. </li></ul><ul><li>Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med 2006; 355(7):685-694. </li></ul>
    37. 39. Diffusion Tensor Imaging to analyse white matter: regions of interest in centrum semiovale © Imperial College London Page Counsell et al Pediatrics 2004
    38. 40. © Imperial College London Page Group analysis of somatosensory fMRI in 11 preterm infants
    39. 41. Four dimensional average brain template from 29 to 44 weeks gestational age
    40. 42. © Imperial College London Page Normal DEHSI Pathology 1.0 1.5 2.0 ADC Values Counsell et al Pediatrics 2004 Diffusion Weighted Imaging in infants with Diffuse Excessive High Signal Intensity in regions of interest within white matter
    41. 43. © Imperial College London Page Krishnan, M. L. et al. Pediatrics 2007
    42. 44. © Imperial College London Page Krishnan, M. L. et al. Pediatrics 2007 Partial regression plots demonstrating components of the multiple regression analysis by plotting residuals from partial regressions
    43. 45. Tract-based Spatial Statistics <ul><li>Example shows 21 preterm infants compared to 6 term control subjects </li></ul>© Imperial College London Page Anjari et al NeuroImage 2007 epub feb 8
    44. 46. © Imperial College London Page White matter regions with significant difference between preterm at term and term-born infants (blue)
    45. 47. Brain regions where white matter microstructure is linearly related to gestation at birth
    46. 48. Brain regions where white matter microstructure is linearly related to severity of respiratory disease
    47. 49. © Imperial College London Page
    48. 50. © Imperial College London Page -4 -2 0 2 4 e( Visual Score | X ) -.02 -.01 0 .01 .02 .03 e( Fractional Anisotropy | X ) -4 -2 0 2 4 e( Visual Score | X ) -.5 0 .5 1 e( MRI-detected Brain Lesions | X ) -3 -2 -1 0 1 2 e( Visual Score | X ) -2 -1 0 1 2 e( Post-menstrual age at Scan | X ) -3 -2 -1 0 1 2 e( Visual Score | X ) -4 -2 0 2 4 e( Gestational Age at Birth | X )
    49. 51. © Imperial College London Page Preterm infants aged 2 years: regions where FA shows linear correlation to developmental score
    50. 52. © Imperial College London Page Preterm infants aged 2 years: regions where FA shows linear correlation to eye-hand co-ordination score
    51. 53. So is it any use? Prediction of outcome for preterm infants by MR <ul><li>Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N.Engl.J.Med. 2006; 355 :685-94. </li></ul><ul><li>Dyet LE, Kennea N, Counsell SJ, Maalouf EF, Ajayi-Obe M, Duggan PJ et al . Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment. Pediatrics 2006; 118 :536-48. </li></ul><ul><li>Mirmiran M, Barnes PD, Keller K, Constantinou JC, Fleisher BE, Hintz SR et al . Neonatal brain magnetic resonance imaging before discharge is better than serial cranial ultrasound in predicting cerebral palsy in very low birth weight preterm infants. Pediatrics 2004; 114 :992-8. </li></ul><ul><li>Miller SP, Ferriero DM, Leonard C, Piecuch R, Glidden DV, Partridge JC et al . Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J.Pediatr. 2005; 147 :609-16. </li></ul>© Imperial College London Page
    52. 54. The neonatal biomarker toolkit © Imperial College London Page paper n gest> Tesla age at scan sequence Miller 86 34 1.5 35-38 T1,2 1998-2003 Woodward 167 31 1.5 40 T1,2 1998-2000 More severe injury generally Dyet 119 30 1.0,1.5 >36 T1,2 1997-2000 less severe injury generally Mirmiran 88 30 and 1250g 1.5 36-40 T1,2
    53. 55. © Imperial College London Page CP Cognitive Motor paper sensitivity specificity sensitivity specificity sensitivity specificity n in group n CP Miller 86 7 (approx, not stated) Woodward 161 17 94 31 89 31 88 30 120 65 84 41 84 65 85 35 Dyet DQ<85 68 4 90 24 1 Mirmiran 61 7 72 91 61 86 89 43
    54. 56. Regions of while matter damage in 12 term infants after birth asphyxia shown by TBSS

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