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.
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.
Malhi et al. 2007
MRI acquisition
MRI BasicsWater = 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
Magnetic Resonance Imaging (MRI)
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
Preprocessing: Structural MRI
Volume/Thickness/Surface Area/Curvature ….
Structural MRIRegion of Interest (ROI)
Voxel based morphometry (SPM/FSL)Surface based morphometry (FreeSurfer)
Structural MRIRegion of Interest (ROI)Voxel based morphometry (SPM/FSL)
Surface based morphometry (FreeSurfer)
Volume
Structural MRIRegion of Interest (ROI)Voxel based morphometry (SPM/FSL)Surface based morphometry (FreeSurfer)
Left
Right
Thickness
Surface Area
Curvature
Gyrification
What can we measure in aRegion of Interest (ROI)?
Total volume
Shape
Average diffusion
Average blood flow
Average level of Glutamate
Average Dopamine levels
Region of Interest
Region of Interest Manual v Automated Caudate
Hippocampus
Manual v FS
ICC 0.79
52% Volume Difference
Manual v FS
ICC 0.95
What’s the problem with ROI?
FreeSurfer Manual
Region of Interest Temporal lobe epilepsy patients (TLE) v Healthy controls (HC)
Manual FreeSurferTLEHC TLEHC
Volu
me
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)
Voxel-based Mophometry
MNI Brain
Original Segmentation Normalisation Modulation Smoothing
VBM - Limitations
Accuracy of the spatial normalisationRegular 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
FreeSurferThe cortex
Volume, thickness or surface area?Volume = surface area * thickness
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
Cortical CurvatureTemporal Lobe Epilepsy (MR-negative)Cortical curvature abnormality in the ipsilateral temporal lobe - Not explained by volume or thicknessPossible surrogate marker for malformations of cortical development
Ronan et al. 2011
FreeSurfer
Cortical Reconstruction
Cortical Analysis - cortical thickness, surface are, volume, cortical folding and curvature
Cortical and sub-cortical segmentation
Surfaces: White and Pial
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
Cortical Thickness
white/gray surface
pial surface• Distance between white and pial surfaces
• One value per vertex
mm
Curvature (Radial)• Circle tangent to
surface at each vertex
• Curvature measure is 1/radius of circle
• One value per vertex
• Signed (sulcus/gyrus)
Inter-subject registrationsubject 1 subject 2 subject 3 subject 4
Template
• 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
Query Design Estimate Contrast - QDEC
Average brain
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
Temporal Lobe Epilepsy (MTS)
Regular VBM- Volume
DBM- Volume/Shape
FreeSurfer- Cortical Thinning
Temporal Lobe Epilepsy (MR-negative)
Volume
Deformation/Shape
Cortical Thinning
Use FreeSurfer
Be Happy
Diffusion MRI
White Matter Organisation
Diffusion Tensor Imaging (DTI)
Diffusion Tensor Imaging (DTI)
Direction of least resistance to water diffusion, λ1
Eigenvectors: the 3 directions
Eigenvalues: the rate of diffusion, λ1, λ2 and λ3
Apparent diffusion Coefficient (Mean diffusivity) = average of λ1, λ2 and λ3
λ1
λ3
λ2
Measuring Anisotropy
Tractography
Tractography
Tractography
Cortical Spinal Tract
Voxel-based Morphometry for dMRI
Issues with regular VBM analysisNot-perfect alignment Smoothing - arbitrary
Fractional Anisotropy (FA) map
Tract-based Spatial StatisticsSmith et al. 2006 – FMRIB
DTI-TK with TBSSHigh level warping using all the tensor information for better alignment
DTI and Schizophrenia
Widespread FA reduction in Schizophrenia versus controls
DeCC neuroimaging
MDD = 153 HC = 153 Matched age and gender Gaussian Process Classifier LOOCV Accuracy = 59%