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Part III Statistical Characterization of Brain Structures via M-reps

Part III Statistical Characterization of Brain Structures via M-reps. Guido Gerig Departments of Computer Science and Psychiatry UNC Chapel Hill. Representative Clinical Study: Neuropathology of Schizophrenia. When does it develop ? Fixed or Progressive ?

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Part III Statistical Characterization of Brain Structures via M-reps

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  1. Part IIIStatistical Characterization of Brain Structures via M-reps Guido Gerig Departments of Computer Science and Psychiatry UNC Chapel Hill Guido Gerig, UNC, Feb. 2003

  2. Representative Clinical Study: Neuropathology of Schizophrenia • When does it develop ? • Fixed or Progressive ? • Neurodevelopmental or Neurodegenerative ? • Neurobiological Correlations ? • Clinical Correlations ? • Treatment Effects ? Noninvasive neuroimaging studies using MRI/fMRI to study morphology and function Guido Gerig, UNC, Feb. 2003

  3. Study: Structural analysis of caudate nucleus in Schizophrenia Processing Steps • Automatic whole brain tissue classification (EM segm.) • User-operated masking of caudate on label image (intra-, interrater reliability > 0.95) • Surface parametrization of caudate shapes  SPHARM & PDM • Alignment/Normalization: Surface Correspondence • Medial mesh generation (m-rep model) Guido Gerig, UNC, Feb. 2003

  4. M-rep PDM Modeling of Caudate Shape PDM M-rep Surface Parametrization Guido Gerig, UNC, Feb. 2003

  5. Ventricles: • lateral ventricle • 3rd ventricle • temporal horn • caudate nucleus • hippocampus Basal Ganglia Netter’s Atlas of Human Anatomy Guido Gerig, UNC, Feb. 2003

  6. Clinical Groups: Healthy controls (N=30) Typical drug treatment (30) Atypical drug treatment (30) Clinical questions: Shape difference between groups? Drug/patient interaction? Location & type of changes CNTL Atyp Typ Caudate Shape Analysis Mean Shapes per Group Guido Gerig, UNC, Feb. 2003

  7. Caudate volume analysis • Significantly larger volumes of SZ versus controls • Trend but not significant difference between Typ/Atyp • Where and what is difference? Guido Gerig, UNC, Feb. 2003 *preliminary analysis, not controlled for age

  8. Mean Shapes CNTL vs. SZ left right Overlay of aligned (transl/rot) original shapes: green: CNTL / purple mesh: SZ Guido Gerig, UNC, Feb. 2003

  9. left right Mean Shapes CNTL vs. SZ Overlay of size normalized* shapes: green: CNTL / purple mesh: SZ *shape should not reflect size change Guido Gerig, UNC, Feb. 2003

  10. Alignment, Correspondence? • Choice of alignment coordinate system? • Establishing correspondence is a key issue for building statistical shape models. • Various methods for definition of correspondence exist (landmarks, high dimensional warping, PDM w. MDL refinement, …). • Resulting eigenmodes of deformation depend on these definitions. • Scaling of objects prior to shape analysis? Guido Gerig, UNC, Feb. 2003

  11. Object Alignment before Shape Analysis 1stelli TR, no scal 1stelli TR, vol scal Procrustes TRS side top top side Guido Gerig, UNC, Feb. 2003

  12. Shape Representation Method: Medial Representation M-rep Implied Surface Skeletal Mesh (sampled) Local Width (Radius) Implied shape represents original shape with 99% volume overlap and =0.05 MAD at boundary (M. Styner, PhD thesis) Guido Gerig, UNC, Feb. 2003

  13. Shape Difference Analysis of M-rep Mesh Position Local Width Mesh distance at corresponding nodes: Object deformation, Bending Grp A Radius difference at corresponding nodes: Local width change A and B aligned, superimposed Grp B Guido Gerig, UNC, Feb. 2003

  14. Shapes represented by m-rep: Significant feature reduction, multi-scale Still: Number of features  sample size. Variability hides shape changes. Shapes not represented by scalar values: Standard MANOVA analysis inappropriate. Often: PCA on features, selection of small # of Eigenmodes, Fisher linear discriminant, leave one out test for classification. But: Fisher LD not robust, #of features?, feature selection?, does PCA reflect group differences? Statistical Analysis Guido Gerig, UNC, Feb. 2003

  15. mesh distance radius Statistical Analysis Guido Gerig, UNC, Feb. 2003

  16. Guido Gerig, UNC, Feb. 2003

  17. Monte Carlo Sampling (m=k=30) Mean differences from 1000 permutations Test original difference 22.8 versus distribution: p=0.025 Permutation Test #experiments Guido Gerig, UNC, Feb. 2003

  18. Typical group shows larger shape difference to controls than atypical group Significant shape difference between typical and atypical treatment group Shape distances not shown in combined SZ versus controls analysis Treatment effect or clinical selection bias? Experimental study design, result need to be verified in cross-validation study Results Caudate Shape AnalysisIntegrated local effects *Non-parametric permutation test Guido Gerig, UNC, Feb. 2003

  19. Right: CNTL – Atyp Right: Atyp – Typ Right: CNTL – Typ Right: CNTL – Atyp -Typ Results Caudate Shape AnalysisComparison of Surfaces • Significant shape changes mostly in the head of the caudate • Shape effect on left side larger than on right side • Local significance tests in progress CNTL Atyp Typ Guido Gerig, UNC, Feb. 2003

  20. Atypical versus Typical drug treatment groups (N = 30) Local Deformation (Euclidean dist. between corresponding nodes) Local significance tests (nonparametric permutation tests) Shape Difference: Where and What?Local Mesh Deformation mesh with node differences p<0.01 p-values per mesh node mesh with nodes p<0.05 Guido Gerig, UNC, Feb. 2003

  21. Atypical versus Typical drug treatment groups (N = 30) Local Deformation (Euclidean dist. between corresponding nodes) Group A Group B Shape Difference: Where and What?Local Mesh Deformation mesh with nodes p<0.05 Guido Gerig, UNC, Feb. 2003

  22. Atypical versus Typical drug treatment groups (N_atyp=N_typ = 30) Local Width Diff. (Radius diff. between corresponding node positions) Local significance tests (nonparametric permutation tests) Shape Difference: Where and What?Local Width Difference mesh with node differences p<0.05 p-values per mesh node mesh with nodes p<0.05 Guido Gerig, UNC, Feb. 2003

  23. Atypical versus Typical drug treatment groups (N_atyp=N_typ = 30) Local Width Diff. (Radius diff. between corresponding node positions) Group A Group B Shape Difference: Where and What?Local Width Difference mesh with nodes p<0.05 Guido Gerig, UNC, Feb. 2003

  24. Atypical versus Typical drug treatment groups (N_atyp=N_typ = 30) Local Width Diff. (Radius diff. between corresponding node positions) Shape Difference: Where and What?Local Width Difference Morphing between Atypical (thinner) and Typical (thicker) Guido Gerig, UNC, Feb. 2003

  25. Discussion Caudate Study Width and mesh deformation mostly in caudate body/head. Secondary mesh deformation posteriorly Typical treatment group differs from Controls, but not Atypical. Clinical implications? Study caudate shape change relative to neighboring shapes. Netter’s Atlas of Human Anatomy Guido Gerig, UNC, Feb. 2003

  26. Study: Hippocampal Shape in Schizophrenia • IRIS: Tool for interactive image segmentation. • Manual contouring in all orthogonal sections. • 2D graphical overlay and 3D reconstruction. • Hippocampus segmentation protocol (following Duvernoy). • Hippocampus: reliability >0.95 intra-, >0.85 inter-rater) Guido Gerig, UNC, Feb. 2003

  27. Hippocampal Volume Analysis • Left smaller than right • SZ smaller than CNTRL, both left and right • Variability SZ larger than CNTL Guido Gerig, UNC, Feb. 2003

  28. 3D Shape Variability: Left Hippocampus of 90 Subjects Guido Gerig, UNC, Feb. 2003

  29. left right in out Hippocampal Shape Analysis Left and right hippocampus: Comparison of mean shapes CNTL-SZ (signed distance magnitude relative to SZ template) Left Right Movie: Flat tail: SZ, curved tail: CNTL Movie: Flat tail: SZ, curved tail: CNTL Guido Gerig, UNC, Feb. 2003

  30. Hippocampus M-rep: Global & Local Statistical Analysis Hippocampus: Integrated difference to template shape (structures size normalized) individual m-rep local group discrimination statistics Width (p<0.75) Deformation (p<0.0001) SZ CNTL SZ CNTL p<0.01 G. Gerig & M. Styner Guido Gerig, UNC, Feb. 2003

  31. Local Statistical Tests Medial representation study confirms: Hippocampal tail is region with significant deformation. Guido Gerig, UNC, Feb. 2003

  32. *Work in progress Keith Muller, Emily Kistner, M. Styner, J. Lieberman, G. Gerig, UNC Chapel Hill Systematic embedding of interaction of age, duration of illness and drug type into local statistical analysis Correction for multiple tests Statistical Analysis of M-rep representations Difference in hippocampus shape between SZ and CNTRL as measured by M-rep deformation *Repeated measures ANOVA, cast as a General Linear Multivariate Model, as in Muller, LaVange, Ramey, and Ramey (1992, JASA). Exploratory analysis included considering both the "UNIREP" Geisser-Greenhouse test and the "MULTIREP" Wilks test. M-rep 3x8 mesh Tail Head Guido Gerig, UNC, Feb. 2003

  33. Model: Row x Col x Drug (y/n) x Age: p = 0.0097 Patient-CNTL Deformation Difference at Age 40 Deformation at mesh nodes (mm) Patient-CNTL Deformation Difference at Age 30 AGE Patient-CNTL Deformation Difference at Age 20 Difference in hippocampus shape between patients and controls: Located mostly in the tail of the hippocampus, becomes more pronounced over time. Tail Head Guido Gerig, UNC, Feb. 2003

  34. Comparison to CNTLs Deformation at mesh nodes (mm) Change in hippocampus shape over ten years for controls Tail Head Guido Gerig, UNC, Feb. 2003

  35. Conclusions • Shape represents changes not reflected by volume analysis • Several clinical studies: Shape discriminates better than volume • M-rep superior to boundary models • separate analysis of local width/bending • results explained in natural language terms • potential to analyze figure-subfigure relationships and figures in anatomic context • Improved statistical framework for discrimination in development Guido Gerig, UNC, Feb. 2003

  36. Acknowledgements • Martin Styner • Sean Ho • Sampath Vetsa • Keith Muller • Jeffrey A. Lieberman • Stephen M. Pizer and M-rep team Talk at: http://midag.cs.unc.edu Guido Gerig, UNC, Feb. 2003

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