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. 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%
Hydrogen Atom
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 Lamour freq, 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

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

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

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

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

13. 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

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

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

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

17. 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)

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

19. 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

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

21. 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

22. 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

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

24. Surfaces: White and Pial

25. 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
The cortical surface is represented by a finite element model using triangles to cover the cortical surface. The reconstruction is the (mostly automated) process of assigning an xyz to each corner of each triangle. Once the xyz of each corner of each triangle is known, then it is possible to characterize the entire cortical surface in terms of area, distance, curvature, and thickness.

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

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

28. Inter-subject registration
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

29. Query Design Estimate Contrast - QDEC
Average brain

30. 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

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

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

33. Use FreeSurfer
Be Happy

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

35. Diffusion Tensor Imaging (DTI)

36. 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

39. Tractography

40. Tractography

41. Tractography
Cortical Spinal Tract

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

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

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