ISMRM Tutorial, Montreal 2011 Computational Anatomy for … · ISMRM Tutorial, Montreal 2011...
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ISMRM Tutorial, Montreal 2011
Computational Anatomy for Subcortical
Population Brain Analysis at 1mm resolution
Michael I Miller [email protected]
The Johns Hopkins University
http://www.cis.jhu.edu/education/tutorials.php
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Outline
• Bijective correspondence: Populations studied via 1-1 mappings to atlas coordinates (LDDMM)
• Atlas’s: Individual and Population
• Statistics: Gaussian Random Fields
• Representation in anatomical coordinates: PCA and surface harmonics
• P-values, clustering, LDA in diseased cohorts
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• Ashburner & Friston (2011) Diffeomorphic registration using geodesic
shooting and Gauss–Newton optimisation. Neuroimage 55:954-967
•Beg,Miller, Trouve, Younes, Computing Large Deformation Metric Mappings
via Geodesic Flows of Diffeomorphisms,, Int. J. Comp. Vision, 2005.
•Christensen Miller Rabbitt, “Deformable Templates via Large Deformation
Kinematics”, IEEE Transactions on Medical Imaging, 1997.
•Grenander, Miller, Computational Anatomy: An Emerging Discipline, Quarterly Applied Math. 1998.
•Khan, Wang, Beg (2008) FreeSurfer-initiated fully-automated subcortical brain
sementation using Large Deformation Diffeomorphic Metric Mapping.
Neuroimage 41: 735-746.
•Ma, Miller, Trouve, Younes, Template Estimation via EM Algorithm,
Neuroimage, 2008.
• Miller, Trouve, Younes, On the Metrics and Euler Lagrange Equations of
Computational Anatomy, Annual Review of Biomedical Engineering, 2002
•Miller, Trouve, Younes , Geodesic Shooting for Computational Anatomy, J.
Math. Imag. And Vision, 2006.
•Oishi, Faria, van Zijl, Mori, MRI Atlas of Human White Matter, 2010 Academic
Press
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•Qiu, Miller “Multi-Structure Network Shape Analysis via Normal Momentum
Maps”, NeuroImage, 2008.
•Qui , Crocetti, Adler, Mahone, Denckla , Miller, Mostofsky (2009) Basal Ganglia
Volume and Shape in Children With Attention Deficit Hyperactivity Disorder.
Am. J. Psychiatry. 166: 74-82.
•Qiu, Brown, Fischl, Ma, Miller: Atlas Generation for Subcortical and Ventricular
Structures With Its Applications in Shape Analysis. IEEE Trans. on Image
Processing 19(6): 1539-1547 (2010)
•Qiu, Adler, Crocetti, Miller, Mostofsky, Basal Ganglia Skills Predict Social
Communication and Motor Dysfunction in Boys with Spectrum Function
Disorder. J. Am. Acad. Child Adolescent Psychiatry 2010 June 49(6):539-551
•Smith, Wang, Cronenwett, Mamah, Barch, Csernansky (2011) Thalamic
morphology in schizophrenia and schizoaffective disorder. J. Psychiatric
Research, 45: 378-385
•Thompson & Apostolova (2007) Computational anatomic methods as applied
to aging and dementia. Brit. J. Radiology 80: S78-S91
•Vaillant, Miller, Trouve, Younes, Neuroimage 2005
• Vercauteren, Pennec, Perchant & Ayache (2009) Diffeomorphic demons:
efficient non-parametric image registration. Neuroimage 45: S61-S72
•Wang, Lee, Bailey, Hartlein, Gado, Miller & Black (2007). Validity of large-
deformation high dimensional brain mapping of the basal ganglia in adults with
Tourette syndrome. Psychiatry Research: Neuroimaging. 154: 181-190.
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Computational Functional Anatomy is the study of structure and function response variables in populations.
Populations are studied via statistics in the template coordinate systems.
Bijective correspondences are used to carry information from one coordinate system to another - we call these bijections diffeomorphisms.
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Populations often involve many modalities: B0, FA, T1, T2, Segmentations,…
Atlas: Electronic form of
anatomical knowledge
Patient data
Bijective
correspondence
via diffeomorphic
mapping
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Original Image
AtlasSingle Subject Template
Image linearly normalized
Linear n
orm
alization
LDD
MM
Image normalized by LDDMMSubject Space
Original Atlas
Atlas superimposed in
the original Image
segmentation
white matter
Voxel-based
analysis
Atlas-based
analysis
Bijective mapping goes forwards and backwards.
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The current state of the art structural validity for subcortical structures in 1mm scale MRI.
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Kappa ~0.8 Overlap of Subcortical StructuresBlue=LDDMM
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Volume Bias ~10%Blue=LDDMM
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Populations are studied via templates with statistics encoded in template coordinates.
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Templates encode populations via bijections.
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Bijective correspondences are generated via large deformation metric mapping (LDDMM) which are flows of the Euler-Lagrange equations.
-bijection is generalization of translations, rotations, scales to infinite dimensions
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x
( )t x y ( , )v y t
1( )x
Bijections are computed via Euler-Lagrange flow equations.
Lagrangian
Eulerian
0( ) ( ( )),
t t tx v x id
1 1 1
0( ) ( ) ( ),
t t tx D x v x id
D=Jacobian
matrixi
j
v
x
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0 6 12
18 24 29
( ) ( ( ))t t t
x v x
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Velocity Field Computed for Curved C-Shapes Mapping
0 6 12
18 24 29
( ) ( ( ))t t t
x v x 713.62I 594.68451.96261.66 I’
1
tI
( ) ( ( ))t t t
x v x
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- subvolumes to connected subvolumes- surfaces to surfaces- sulcal curves to sulcal curves
The Euler-Lagrange equations are used to constrain the generation of bijectionsbecause they support large – high dimensional - deformations which carry structures consistently:
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Bijective Euler-Lagrange Flows (Diffeomorphisms)
Euler equation flowNo Euler equation flow
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Simple example of large deformations in human anatomy
Closed lateral ventricles Expanded lateral ventricles
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0
1000
2000
3000
4000
5000
6000
2001 2 3 4 5 6 7 8 9 10
0
200
400
600
800
1000
1200
1400
Jan Feb Mar Apr May Jun july Aug Sep Oct Nov Dec Jan
2010 2011LD
DM
M c
alls
month
ly
Reg
iste
red M
RIS
tudio
Users
Cumlative
Yearly
Bijective Mapping Available via MRIStudiowww.mristudio.org
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Individual Templates and
Population Templates
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• Full segmentation (200 structures)• Stereotaxic (MNI and Talairach)• Gray / white matter assignment • Modern Brodmann’s map• Population-averaged tract coordinates
LDDMM
JHU-MNI Atlas www.mristudio.org
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Building Population AtlasesAdult atlases
Neonate atlases
Population Atlas
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Population based template generation
via EM Algorithm
The template to be estimated is an unknown deformation of an
anatomy in the “center” of a collection of human anatomies -
indistinguishable from other anatomical configurations - not an
arithmetic average.
The complete data are the deformations generating the
(unknown) template mapping to the population data.
•E-step: generates the conditional mean deformations given the
previous iterate template-old and the observed MRI imagery.
•M-step: generates template-new maximizing the complete-data
posterior distribution with respect to the unknown deformation of
template-old.
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EM Algorithm- Iteration 1
0I
1
0M1
tempI
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EM Algorithm: Iteration n
0
nMn
tempI0I
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EM Algorithm: Convergence
0M
tempI
0I
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LDDMM Subcortical Atlas: An Example
https://caportal.cis.jhu.edu/pipelines/atlases/human
The atlas was built based on the manually labeled image volumes of 41 subjects
using large deformation diffeomorphic metric template mapping algorithm. The
population includes 10 young adults, 10 middle age adults, 10 healthy elders, and
11 Alzheimer’s pateients.
up_1280_800_15.mpg
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Statisticsfor
Populations
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Statistics are computed using Gaussian random fields on the response variables and complete orthonormal bases indexed over the anatomical coordinates.
Statistics
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Statistics are studied as pairs (F,M) of function F on
manifolds M:
• Statistics performed in the coordinates of M
• Statistics via GRF models in H(M)
( )
( , )Element AnatomicalHilbert ManifoldSpaceH MwithCON
F M Hilbert Space
H(M)
with a CON base.
structure-function Laplace-Beltrami orresponse-variables PCA CON Basis
k k
k
F F
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Statistics are obtained via template injection onto
the targets. The bijection encodes in template
coordinates the target shapes.
hippocampus
hippocampusQiu, Miller “Multi-Structure Network Shape Analysis via Normal Momentum Maps”, NeuroImage, 2008. caudate
ventricle hippocampus
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PREDICT STUDY: template structures carry a set of response variables and surface expansion functions.
Five expansion functions on the template.
A response variable Fk can be generated by taking the Jacobian determinant of the template bijection onto the target and projecting onto the basis.
response-variables
k k
k
F F
Red Compression
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The Atlas to Target Statistical Pipeline
Putamen Template Injected
into Targets
Shape Encoded on
Template Surface
Structures via
Random Field
Models
MRI Target
Putamen
Red CompressionTemplate
Putamen
structure-function Laplace-Beltrami orresponse-variables PCA Basis
k k
k
F F
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Template
Caudate Template Injected
into Targets
Shape Encoded on
Template Surface
Structures via
Random Field
Models
MRI Target
Caudate
structure-function Laplace-Beltrami orresponse-variables PCA Basis
k k
k
F F
The Atlas to Target Statistical Pipeline
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The PREDICT Study: An Example of Subcortical Shape Analysis
Human striatal studies of HD patients
Far from
onset
Close to
onset
Early
affected
Younes, Paulsen, Ross, et. All.,Heterogeneous atrophy of subcortical structures in prodromal HD as
revealed by statistical shape analysis, submitted.
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Curved Coordinate System Representations via an
Orthonormal Basis
PCA and Surface Harmonics
structure-function Laplace-Beltrami orresponse-variables PCA Basis
k k
k
F F
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PCA, one orthonormal base in Anatomical Coordinates
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Principle Components are an orthonormal basis which can be used, requiring training data.
caudate
putamen
expansion
shrinkage
PCA mode 1 PCA mode 2 PCA mode 3
response-variables PCA Basis
k k
k
F F
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Laplace-Beltrami, another orthonormalbase in anatomical coordinates not requiring training data (generalization of the Fourier basis)
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Spherical
Harmonics:
one example
Laplace-
Beltrami
basis for the sphere.
Complete orthonormal bases via harmonics of the
Laplacian operator; like the Fourier basis no training
data required.
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response-variables Laplace-Beltrami
k k
k
F F
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response-variables Laplace-Beltrami
k k
k
F F
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Laplace-Beltrami Orthonormal Base
response-variables Laplace-Beltrami
k k
k
F F
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1.5
2
2.5
3
3.5
-0.05
0
0.05
Amygdala
Hippocampus
LB Basis 1 LB Basis 2 LB Basis 3
Laplace-Beltrami Surface Basis
response-variables Laplace-Beltrami
k k
k
F F
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Atrophy patterns: PREDICTRank sum tests thresholded at 5% family-wise significance (significant regions in red)
Younes, Paulsen, Ross, et. All.,Heterogeneous atrophy of subcortical structures in prodromal HD as
revealed by statistical shape analysis, submitted.
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Atrophy pattern: Left Putamen
Two views of the atrophy pattern estimated on the left putamen
Younes, Paulsen, Ross, et. All.,Heterogeneous atrophy of subcortical structures in prodromal HD as
revealed by statistical shape analysis, submitted.
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Atrophy pattern: Right Putamen
Two views of the atrophy pattern estimated on the right putamen
Younes, Paulsen, Ross, et. All.,Heterogeneous atrophy of subcortical structures in prodromal HD as
revealed by statistical shape analysis, submitted.
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Atrophy Pattern: Left Caudate
Two views of the atrophy pattern estimated on the left caudate
Younes, Paulsen, Ross, et. All.,Heterogeneous atrophy of subcortical structures in prodromal HD as
revealed by statistical shape analysis, submitted.
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Atrophy Pattern: Right Caudate
Two views of the atrophy pattern estimated on the right caudate
Younes, Paulsen, Ross, et. All.,Heterogeneous atrophy of subcortical structures in prodromal HD as
revealed by statistical shape analysis, submitted.
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Clustering
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Clustering Based on Significant Discriminating Features
Left putamen Right putamen
Left caudate Right caudate
k k
k Features
F F
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Statistical Significance
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Left
putamen
Right
putamen
Left
Caudate
Right
Caudate
Volume 0.0006 0.00005 0.0066 0.0031
Jacobian <0.0001 .0001 0.011 .0015
Jacobian centered .0011 .0003 .0014 .043
Tangential atrophy 0.0005 <0.0001 0.005 0.0004
Centered T. atrophy 0.094 0.0012 0.0001 0.0024
Jacobian on
harmonics
.0005 .0001 <.0001 .035
PCA on momentum .0011 .001 .0034 0.0088
PCA on jacobian .0004 <.0001 .0012 .0013
P-values
p-value accuracy: .0001
Younes, Paulsen, Ross, et. All.,Heterogeneous atrophy of subcortical structures in prodromal HD as
revealed by statistical shape analysis, submitted.
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The Locality of Shape Change inADHD
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ADHD: Basal Ganglia Shape AnalysisN gender Age(SD)
Female Male
CON 66 31 35 10.5 (1.3)
ADHD 47 20 27 10.4 (1.2)
Caudate
Putamen
Globus Pallidus
Basal Ganglia Template
compress
expand
Qui A, Crocetti D, Adler M,
Mahone EM, Denckla M,
Miller MI, Mostofsky SH
(2009) Basal Ganglia Volume
and Shape in Children With
Attention Deficit Hyperactivity
Disorder. Am. J. Psychiatry.
166: 74-82.
Reconstructions in
statistically
significant
Eigenfunctions
p<.05
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shrinkageexpansion
Subcortical Shape Analysis in Dementia
Groups Ngender age
(mean±SD)male female
control 133 71 62 75.8±4.90
MCI 170 119 51 74.6±7.39
AD 80 49 31 75.2±7.62
CON vs. AD
Am
V
Hp
V
Reconstructions in statistically significant p<.05 Anqi Qiu Christine Fennema Notestine, Anders M. Dale, Michael I. Miller, and the Alzheimer’s Disease Neuroimaging Initiative, "Regional Subcortical Shape Abnormalities in Mild Cognitive Impairment and Alzheimer's Disease ", NeuroImage,45:656-661, 2009
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The End