desiree abdurrachim morphometric analysis of the hippocampus in r6/1 hd mouse model internship...
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Desiree Abdurrachim
Morphometric analysis of the hippocampus in R6/1 HD mouse model
InternshipAugust – October 2007
Desiree Abdurrachim
Supervisor: Leigh Johnston (HFI)
Gary Egan (HFI)Bart ter Haar Romenij (TU/e)
Desiree Abdurrachim
HFI?• Australian’s Brain Research Institute In
Melbourne, Australia– Brain Development, Brain Injury and Repair, S
ystem Neurobiology, Neuroimaging!, …
• Neuroimaging Group, led by Gary Egan– Human research
– MR methods research
– Neuroinformatics research
– Animal research
Desiree Abdurrachim
Outlines
• Introduction
• Methods
• Results
• Conclusions
• Future work
Desiree Abdurrachim
Outlines
• Introduction
• Methods
• Results
• Conclusions
• Future work
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
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
Desiree Abdurrachim
Outlines
• Introduction
• Methods
• Results
• Conclusions
• Future work
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
Desiree Abdurrachim
Methods [2/7]
Hippocampus segmentation
Hemisphere extraction
Brain extraction
Volumetric Study Shape Analysis
Desiree Abdurrachim
Methods [3/7]
Brain extraction
using BrainSuite (USC) [1]Hippocampus segmentation
Hemisphere extraction
Brain extraction
Volumetric Study Shape Analysis
Desiree Abdurrachim
Methods [4/7]
• Manual segmentation• Using FSL (Oxford) [2]• Mn enhanced voxels• Reference: registration of B
rookhaven digital atlas [4]
Hippocampus segmentation
Hemisphere extraction
Brain extraction
Volumetric Study Shape Analysis
Desiree Abdurrachim
Methods [5/7]
Hippocampus segmentation
Hemisphere extraction
Brain extraction
Volumetric Study Shape Analysis
• Connected component analysis• Centre of mass• Determine region
Desiree Abdurrachim
Methods [6/7]
Hippocampus segmentation
Hemisphere extraction
Brain extraction
Volumetric Study Shape Analysis
• Volume of:– Brain– Hippocampus
• Volume = # voxels x resolutions
Desiree Abdurrachim
Methods [7/7]
Hippocampus segmentation
Hemisphere extraction
Brain extraction
Volumetric Study Shape 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]
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
Desiree Abdurrachim
SPHARM Shape Analysis [2/6]
SPHARM Segmentation Object meshing
Spherical parameterization
Alignment &Comparing points
Statistical analysis
(x,y,z)
(Θ,φ)
Modified from [Styner, 2006]
Generating SPHARM Object
Desiree Abdurrachim
SPHARM Shape Analysis [3/6]
Generate SPHARM Object [1/2]
• Calculate SPHARM Coefficients – position (x,y,z) from the mesh (obje
ct space)
– (θ,φ) parameter from the sphere (parameter space)
0
),(),(l
l
lm
ml
ml YCx
imml
ml eP
ml
mllY )(cos
)!(
)!(
4
)12(),(
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
0
),(),(l
l
lm
ml
ml YCx
4002 sampling points,
12th degree
Desiree Abdurrachim
SPHARM Shape Analysis [5/6]
SPHARM Segmentation Object meshing
Spherical parameterization
Alignment &Comparing points
Statistical analysis
(x,y,z)
(Θ,φ)
Modified from [Styner, 2006]Shape analysis
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
Desiree Abdurrachim
Outlines
• Introduction
• Methods
• Results
• Conclusions
• Future work
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 %
Desiree Abdurrachim
Results – shape analysis [1/2]
• Global shape changes
– Left hippocampus : p-value = 0.0362– Right hippocampus : p-value = 0.00005
Desiree Abdurrachim
Results – shape analysis [2/2]
• Local shape changes:– Left
– Right
Desiree Abdurrachim
Outlines
• Introduction
• Methods
• Results
• Conclusions
• Future work
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
Desiree Abdurrachim
Outlines
• Introduction
• Methods
• Results
• Conclusions
• Future work
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
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/
[4] http://www.bnl.gov/CTN/mouse/