1. Desiree Abdurrachim 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. Desiree Abdurrachim 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. Desiree Abdurrachim Outlines Introduction Methods Results Conclusions Future work

4. Desiree Abdurrachim Outlines Introduction Methods Results Conclusions Future work

5. Desiree Abdurrachim 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. Desiree Abdurrachim 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. Desiree Abdurrachim Outlines Introduction Methods Results Conclusions Future work

8. Desiree Abdurrachim 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. Desiree Abdurrachim Methods [2/7] Hippocampus segmentation Hemisphere extraction Brain extraction Volumetric StudyShape Analysis

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

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

12. Desiree Abdurrachim Methods [5/7] Hippocampus segmentation Hemisphere extraction Brain extraction Volumetric StudyShape Analysis Connected component analysis Centre of mass Determine region

13. Desiree Abdurrachim Methods [6/7] Hippocampus segmentation Hemisphere extraction Brain extraction Volumetric StudyShape Analysis Volume of: –Brain –Hippocampus Volume = # voxels x resolutions

14. Desiree Abdurrachim Methods [7/7] Hippocampus segmentation Hemisphere extraction Brain extraction Volumetric StudyShape Analysis 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. Desiree Abdurrachim 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. Desiree Abdurrachim SPHARM Shape Analysis [2/6] SPHARM Segmentation Object meshing Spherical parameterization Alignment & Comparing points Statistical analysis (x,y,z) (Θ,φ)(Θ,φ) Modified from [Styner, 2006] Generating SPHARM Object

17. Desiree Abdurrachim 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. Desiree Abdurrachim 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, 12 th degree

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

20. Desiree Abdurrachim 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. Desiree Abdurrachim Outlines Introduction Methods Results Conclusions Future work

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

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

25. Desiree Abdurrachim Outlines Introduction Methods Results Conclusions Future work

26. Desiree Abdurrachim 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. Desiree Abdurrachim Outlines Introduction Methods Results Conclusions Future work

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