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

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)
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
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Human research
MR methods research
Neuroinformatics research
Animal research
Desiree Abdurrachim
Outlines
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Introduction
Methods
Results
Conclusions
Future work
Desiree Abdurrachim
Outlines
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Introduction
Methods
Results
Conclusions
Future work
Desiree Abdurrachim
Introduction [1/2]
• What is Huntington’s Disease (HD)?
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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
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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]
Brain
extraction
Hippocampus
segmentation
Hemisphere
extraction
Volumetric Study
Desiree Abdurrachim
Shape Analysis
Methods [3/7]
Brain
extraction
Hippocampus
segmentation
Brain extraction
 using BrainSuite (USC) [1]
Hemisphere
extraction
Volumetric Study
Shape Analysis
Desiree Abdurrachim
Methods [4/7]
Brain
extraction
Hippocampus
segmentation
Hemisphere
extraction
Volumetric Study
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Manual segmentation
Using FSL (Oxford) [2]
Mn enhanced voxels
Reference: registration of
Brookhaven digital atlas [4]
Shape Analysis
Desiree Abdurrachim
Methods [5/7]
Brain
extraction
• Connected component analysis
• Centre of mass
• Determine region
Hippocampus
segmentation
Hemisphere
extraction
Volumetric Study
Shape Analysis
Desiree Abdurrachim
Methods [6/7]
Brain
extraction
Hippocampus
segmentation
Hemisphere
extraction
Volumetric Study
• Volume of:
– Brain
– Hippocampus
• Volume =
# voxels x resolutions
Shape Analysis
Desiree Abdurrachim
Methods [7/7]
Brain
extraction
Hippocampus
segmentation
Hemisphere
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]
Generating SPHARM Object
Segmentation
Object meshing (x,y,z)
SPHARM
Alignment &
Comparing points
(Θ,φ)
Spherical
parameterization
Modified from [Styner, 2006]
Desiree Abdurrachim
Statistical
analysis
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)

l
x( ,  )    C Y ( ,  )
l 0 m   l
Yl m ( ,  ) 
m m
l l
(2l  1) (l  m)! m
Pl (cos )eim
4 (l  m)!
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

l
x( ,  )    C Y ( ,  )
l 0 m   l
m m
l l
4002 sampling points,
12th degree
Desiree Abdurrachim
SPHARM Shape Analysis [5/6]
Segmentation
Object meshing (x,y,z)
SPHARM
Alignment &
Comparing points
(Θ,φ)
Spherical
parameterization
Modified from [Styner, 2006]
Statistical
analysis
Desiree Abdurrachim
Shape analysis
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
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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
– In WT
: 2.9 %
: 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
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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
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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/
Desiree Abdurrachim