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Morphometric analysis of the hippocampus in R6/1 HD mouse model

Morphometric analysis of the hippocampus in R6/1 HD mouse model. Internship August – October 2007 Desiree Abdurrachim Supervisor: Leigh Johnston (HFI) Gary Egan (HFI) Bart ter Haar Romenij (TU/e). HFI? Australian’s Brain Research Institute In Melbourne, Australia

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Morphometric analysis of the hippocampus in R6/1 HD mouse model

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  1. Morphometric analysis of the hippocampus in R6/1 HD mouse model Internship August – October 2007 Desiree Abdurrachim Supervisor: Leigh Johnston (HFI) Gary Egan (HFI) Bart ter Haar Romenij (TU/e)

  2. HFI? • Australian’s Brain Research Institute In Melbourne, Australia • Brain Development, Brain Injury and Repair, System Neurobiology, Neuroimaging!, … • Neuroimaging Group, led by Gary Egan • Human research • MR methods research • Neuroinformatics research • Animal research

  3. Outlines • Introduction • Methods • Results • Conclusions • Future work

  4. Outlines • Introduction • Methods • Results • Conclusions • Future work

  5. Introduction [1/2] • What is Huntington’s Disease (HD)? • Neurodegenerative disorder • Mutation in coding region of the huntingtin gene • Atrophy in almost every brain structure • Chorea, cognitive impairment, death after 10-15 years onset • Neuroimaging to investigate the HD • Mouse model • Similar condition to human • Study pathology and trial therapies

  6. Introduction [2/2] • A R6/1 mouse model has been developed to investigate brain structural changes • Hippocampus  role in memory and spatial navigation • Questions: • Significant atrophy? • Significant shape changes? www.mouseimaging.ca

  7. Outlines • Introduction • Methods • Results • Conclusions • Future work

  8. Methods [1/7] • Image acquisition • 6 HD and 7 WT (26 week old) mice • Manganese-enhanced T1W MRI • Image analysis • Volumetric Study • Shape analysis

  9. Brain extraction Hippocampus segmentation Hemisphere extraction Volumetric Study Shape Analysis Methods [2/7]

  10. Brain extraction Hippocampus segmentation Hemisphere extraction Volumetric Study Shape Analysis Methods [3/7] Brain extraction  using BrainSuite (USC) [1]

  11. Brain extraction Hippocampus segmentation Hemisphere extraction Volumetric Study Shape Analysis Methods [4/7] • Manual segmentation • Using FSL (Oxford) [2] • Mn enhanced voxels • Reference: registration of Brookhaven digital atlas [4]

  12. Brain extraction Hippocampus segmentation Hemisphere extraction Volumetric Study Shape Analysis Methods [5/7] • Connected component analysis • Centre of mass • Determine region

  13. Brain extraction Hippocampus segmentation Hemisphere extraction Volumetric Study Shape Analysis Methods [6/7] • Volume of: • Brain • Hippocampus • Volume = # voxels x resolutions

  14. Brain extraction Hippocampus segmentation Hemisphere extraction Volumetric Study Shape Analysis Methods [7/7] • Define shape descriptors: • deformation field, landmark, shape parameters, skeleton • Find correspondence between object • Hippocampus • Spherical topology • Spherical harmonics (SPHARM)-based analysis • Using open-source tool, UNC [3]

  15. SPHARM Shape Analysis [1/6] • SPHARM: a function that describes an object with spherical topology • SPHARM coefficients describe the shape • Different SPHARM degrees give different shape

  16. (x,y,z) SPHARM Object meshing Alignment & Comparing points Segmentation (Θ,φ) Spherical parameterization Statistical analysis SPHARM Shape Analysis [2/6] Generating SPHARM Object Modified from [Styner, 2006]

  17. SPHARM Shape Analysis [3/6] Generate SPHARM Object [1/2] • Calculate SPHARM Coefficients • position (x,y,z)  from the mesh (object space) • (θ,φ) parameter from the sphere (parameter space)

  18. SPHARM Shape Analysis [4/6] Generate SPHARM Object [2/2] • Regenerating the surface • Sampling points on sphere homogenously • Recalculate position (x,y,z) on object space 4002 sampling points, 12th degree

  19. (x,y,z) SPHARM Object meshing Alignment & Comparing points Segmentation (Θ,φ) Spherical parameterization Statistical analysis SPHARM Shape Analysis [5/6] Modified from [Styner, 2006] Shape analysis

  20. SPHARM Shape Analysis [6/6] • Correspondence  alignment • Compare points between objects • Calculate Euclidean distance (d) • For each particular point, from the distribution of d in HD and WT : • apply Student’s t-test  p-value

  21. Outlines • Introduction • Methods • Results • Conclusions • Future work

  22. Results – volumetric study • Atrophy: • Brain : 24.58% (p-value = 0.0049) • Hippocampus: 25.68% (p-value = 0.0007) • Hippocampus to brain ratio • In HD : 2.9 % • In WT : 2.9 %

  23. Results – shape analysis [1/2] • Global shape changes • Left hippocampus : p-value = 0.0362 • Right hippocampus : p-value = 0.00005

  24. Results – shape analysis [2/2] • Local shape changes: • Left • Right

  25. Outlines • Introduction • Methods • Results • Conclusions • Future work

  26. Conclusions • Volumetric study and shape analysis for morphometric study in HD mice • Significant atrophy of the brain and the hippocampus in HD • Atrophy of the hippocampus is due to global brain shrinkage • Significant hippocampus shape changes in HD • Integration with histological studies

  27. Outlines • Introduction • Methods • Results • Conclusions • Future work

  28. Future work • Larger number of samples • Analysis on other time points • More careful observation on choosing the SPHARM degree • Re-segmentation of the hippocampus due to manual segmentation  results independent of segmentation • Comparison with other shape descriptor to find the best shape correspondence • A good visualization tool

  29. References [1] http://brainsuite.usc.edu/ [2] http://www.fmrib.ox.ac.uk/fsl/ [3] http://www.ia.unc.edu/dev/download/shapeAnalysis/ [4] http://www.bnl.gov/CTN/mouse/

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