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Neuroimaging Processing : Overview , Limitations , pitfalls, etc . etc.

Neuroimaging Processing : Overview , Limitations , pitfalls, etc . etc. Neuroimaging. Neuroimaging includes the use of various techniques to either directly or indirectly image the structure or function of the brain.

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Neuroimaging Processing : Overview , Limitations , pitfalls, etc . etc.

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  1. Neuroimaging Processing :Overview, Limitations, pitfalls, etc. etc.

  2. Neuroimaging • Neuroimaging includes the use of various techniques to either directly or indirectly image the structure or function of the brain. • Structural neuroimaging deals with the structure of the brain (e.g. shows contrast between different tissues: cerebrospinal fluid, grey matter, white matter). • Functional neuroimaging is used to indirectly measure brain function (e.g. neural activity) • Molecular neuroimaging measures biological processes in the brain at the molecular and cellular level.

  3. Malhi et al. 2007

  4. MRI acquisition

  5. Hydrogen Atom MRI Basics • Water = H2O • Each Hydrogen = one proton • Protons Spin • Generates detectable signal in externally applied magnetic field: that is, it causes protons to precess at a frequency proportional to the strength of the magnetic field – the ‘resonant’ frequency • Water Content of • GM 70% • WM 85% • Blood 93% PROTON

  6. Magnetic Resonance Imaging (MRI)

  7. Magnetic Resonance Imaging (MRI) Excitation • Radio frequency (RF) pulse is applied at the precession frequency (Lamour Frequency) • Sending an RF pulse at Lamourfreq, particular amplitude and length of time – possible to flip the net magnetism 90° - perpendicular to Magnetic Field (B0) Relaxation • T1-weighted is the time it takes for the protons to relax to B0 • Not all protons bound by their molecules in same way, dependant on tissue type

  8. Preprocessing: Structural MRI Volume/Thickness/Surface Area/Curvature ….

  9. Structural MRI • Region of Interest (ROI) • Voxel based morphometry (SPM/FSL) • Surface based morphometry (FreeSurfer)

  10. Structural MRI • Region of Interest (ROI) • Voxel based morphometry (SPM/FSL) • Surface based morphometry (FreeSurfer) Volume

  11. Structural MRI • Region of Interest (ROI) • Voxel based morphometry (SPM/FSL) • Surface based morphometry (FreeSurfer) Thickness Surface Area Curvature Gyrification Left Right

  12. Region of Interest What can we measure in a Region of Interest (ROI)? Total volume Shape Average diffusion Average blood flow Average level of Glutamate Average Dopamine levels

  13. Region of Interest • Manual v Automated Caudate Manual v FS ICC 0.95 Hippocampus Manual v FS ICC 0.79 52% Volume Difference

  14. What’s the problem with ROI? FreeSurfer Manual

  15. Region of Interest • Temporal lobe epilepsy patients (TLE) v Healthy controls (HC) Volume Manual FreeSurfer HC TLE HC TLE

  16. Voxel-based Mophometry • Statistical Parametric Mapping (SPM) • FMRIB Software Library (FSL) • No a priori hypothesis • Volume Change • Chronic Schizophrenia patients after Clozapine treatment for 6 months < Healthy Controls (FDR correction p<0.05)

  17. Voxel-based Mophometry Segmentation Normalisation Modulation Smoothing Original MNI Brain

  18. VBM - Limitations • Accuracy of the spatial normalisation • Regular SPM uses 1000 parameters – just fits overall shape of the brain -mis-registrations • Deformation-based morphometry (e.g. DARTEL) – deformation field is analysed • Grey matter matched with grey matter – doesn't’t indicate whether sulci/gyri are aligned

  19. FreeSurfer • The cortex • Volume, thickness or surface area? • Volume = surface area * thickness

  20. Volume, thickness & surface area • Related but don’t necessarily track each other .... • Morphometry Differences between Young, Elderly and Mild Alzheimer’s in entorhinal cortex. *p<0.05 Dickerson et al.2007

  21. Cortical Curvature • Temporal Lobe Epilepsy (MR-negative) • Cortical curvature abnormality in the ipsilateral temporal lobe - Not explained by volume or thickness • Possible surrogate marker for malformations of cortical development Ronan et al. 2011

  22. FreeSurfer • Cortical Reconstruction • Cortical Analysis - cortical thickness, surface are, volume, cortical folding and curvature • Cortical and sub-cortical segmentation

  23. Surfaces: White and Pial

  24. Surface Model • Mesh (“Finite Element”) • Vertex = point of 6 triangles • XYZ at each vertex • Triangles/Surface Element ~ 150,000 • Area, Curvature, Thickness, Volume at each vertex

  25. Cortical Thickness pial surface • Distance between white and pial surfaces • One value per vertex mm white/gray surface

  26. Curvature (Radial) • Circle tangent to surface at each vertex • Curvature measure is 1/radius of circle • One value per vertex • Signed (sulcus/gyrus)

  27. Inter-subject registration subject 1 subject 2 subject 3 subject 4 • Gyrus-to-Gyrus and Sulcus-to-Sulcus • Some minor folding patterns won’t line up • Atlas registration is probabilistic, most variable regions get less weight. • Done automatically in recon-all Template

  28. Query Design Estimate Contrast - QDEC Average brain

  29. Advantages of FreeSurfer • Analysis of separate components of volume – thickness and surface area • Geometry is used for inter-subject registration (major sulcal and gyral patterns) • 2-D surface smoothing versus 3-D volume smoothing – more biologically meaningful

  30. Temporal Lobe Epilepsy (MTS) Regular VBM - Volume DBM - Volume/Shape FreeSurfer - Cortical Thinning

  31. Temporal Lobe Epilepsy (MR-negative) Volume Deformation/ Shape Cortical Thinning

  32. Use FreeSurfer Be Happy

  33. Diffusion MRI Diffusion Tensor Imaging (DTI) White Matter Organisation

  34. Diffusion Tensor Imaging (DTI)

  35. Measuring Anisotropy λ1 λ3 λ2 Eigenvectors: the 3 directions Eigenvalues: the rate of diffusion, λ1, λ2 and λ3 Apparent diffusion Coefficient (Mean diffusivity) = average of λ1, λ2 and λ3 Direction of least resistance to water diffusion, λ1

  36. Tractography

  37. Tractography

  38. Tractography Cortical Spinal Tract

  39. Voxel-based Morphometry for dMRI • Issues with regular VBM analysis • Not-perfect alignment • Smoothing - arbitrary • Tract-based Spatial Statistics • Smith et al. 2006 – FMRIB Fractional Anisotropy (FA) map • DTI-TK with TBSS • High level warping using all the tensor information for better alignment

  40. DTI and Schizophrenia Widespread FA reduction in Schizophrenia versus controls

  41. DeCC neuroimaging • MDD = 153 • HC = 153 • Matched age and gender • Gaussian Process Classifier • LOOCV • Accuracy = 59%

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