random field theory rumana chowdhury and nagako murase methods for dummies november 2010
TRANSCRIPT
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Random field theory
Rumana Chowdhury and Nagako Murase
Methods for Dummies
November 2010
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Overview
Part 1• Multiple comparisons• Family-wise error• Bonferroni correction• Spatial correlation
Part 2• Solution = Random Field Theory• Example in SPM
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Normalisation
Statistical Parametric Map
Image time-series
Parameter estimates
General Linear ModelRealignment Smoothing
Design matrix
Anatomicalreference
Spatial filter
StatisticalInference
RFT
p <0.05p <0.05
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Voxel
• Raw data collected as group of voxels
• 3D, volumetric pixel– Location– Value
• Calculate a test statistic for each voxel
• Many many many voxels…
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Null hypothesis• Determine if value of single specified voxel is
significant
• Create a null hypothesis, H0 (activation is zero)
= data randomly distributed, Gaussian distribution of noise
• Compare our voxel’s value to a null distribution
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Single voxel level statistics
•Perform t-tests
•Decision rule (threshold) u, determines false +ve rate
•Choose u to give acceptable α under H0
= P(type I error) i.e. chance we are wrong when rejecting the null hypothesis
t
u
= p(t>u|H)
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Multiple comparisons problem
• fMRI – lots of voxels, lots of t-tests
• If use same threshold, higher probability of obtaining at least 1 false +ve
t
u
t
u
t
u
t
u
t
u
e.g. for alpha=0.05, 10000 voxels: expect 500 false positives
11.3% 11.3% 12.5% 10.8% 11.5% 10.0% 10.7% 11.2% 10.2% 9.5%
Use of ‘uncorrected’ p-value, =0.1
Percentage of Null Pixels that are False Positives
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Family-wise error
• In fMRI = volume (family) of voxel statistics
• Family-wise null hypothesis = activation is zero everywhere
• Family Wise Error (FWE) = 1 false positive anywhere
• FWE rate = ‘corrected’ p-value
FWE
Use of ‘corrected’ p-value, α =0.1
Use of ‘uncorrected’ p-value, α =0.1
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Definitions
Univariate statisticsFunctional imaging1 observed data many voxels
1 statistical value family of statistical values
type I error rate family-wise error rate (FWE)
null hypothesis family-wise null hypothesis
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Thresholding
•Height thresholding
•This gives us localizing power
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Bonferroni correctionp = /n
Corrected p-valueα = acceptable Type 1 error raten = number of tests
•The Family-Wise Error rate (FWE), α, for a family of N independent voxels is
α = Nv•where v is the voxel-wise error rate. Therefore, to ensure a particular FWE set
v = α / NBut…
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Spatial Correlation
Averaging over one voxel and its neighbours (independent
observations)Usually weighted average using a
(Gaussian) smoothing kernel
•Dependence between voxels : physiological signal
data acquisition
spatial preprocessing
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The problem with Bonferroni
0.05/10000 = 0.000005Z score 4.42
Fewer independent observations than there are voxels
Bonferroni is too conservative (high false negative)
Appropriate correction:0.05/100 = 0.0005
Z score 3.29
100 x 100 voxels – normally distributed independent random numbers
Averaged 10x10
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• Not making inferences on single voxels
• Take into account spatial relationships
• Topology
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Euler
• Leonhard Euler (1797-1783), Swiss mathematician• Seven bridges of Kӧnisberg
“the problem has no solution!”
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Euler characteristic: the beginnings
• ECV-E+F = 2
• Number of polyhedra (P)V-E+F-P=1
• Holes & handlesreduce by 1
• Topology…0d - 1d + 2d - 3d + 4d…etc
8 – 12 + 6 = 2
16 – 28 + 16 – 3 = 1
EC is a topological measure…
0 (product of 2 circles)
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(a little bit more background)
• Robert J Adler (1981): relationship between topology of random field (local maxima) and EC
• Apply a threshold to random field; regions above = excursion sets
• EC is a topological measure of excursion set
• Expected EC is a good approximation of FWE at higher threshold
• Random field theory uses the expected EC
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Random field theory: overview• Consider statistic image as lattice representation of a continuous
random field
• Takes into account smoothness and shape of the data as well as number of voxels to apply an appropriate threshold
lattice representation
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References• An Introduction to Random Field Theory (Chapter 14) Human Brain
Mapping• Developments in Random Field Theory (Chapter 15), KJ Worsley• Previous MfD slides:
http://www.fil.ion.ucl.ac.uk/mfd/page2/page2.html• Guillaume Flandin’s slides:
http://www.fil.ion.ucl.ac.uk/spm/course/slides10-meeg/• Will Penny’s slides:
http://www.fil.ion.ucl.ac.uk/spm/course/slides05/ppt/infer.ppt#324,1,Random Field Theory
• R. Adler’s website: http://webee.technion.ac.il/people/adler/research.html
• CBU imaging wiki: http://imaging.mrc-cbu.cam.ac.uk/imaging/PrinciplesRandomFields
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RFT for dummies - Part II 21
Random Field Theory
Part II
Nagako Murase
17/11/2010
21
Methods for Dummies 2010
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Overview A large volume of imaging data
Multiple comparison problem
Bonferroni correction α=PFWE/nCorrected p value
FWE rate is too lowto reject the null hypothesis
Too false negative
Never use this.
It is because Bonferroni correction is based on the assuption that all the voxels are independent.
Random field theory (RFT)
α = PFWE ≒ E[EC] Corrected p value
<smoothing >
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Process of RFT application: 3 steps
1st
Smoothing →Estimation of smoothness (spatial
correlation)
2nd
Applying RFT
3rd
Obtaining PFWE
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realignment &motion
correctionsmoothing
normalisation
General Linear Modelmodel fittingstatistic image
Corrected thresholds & p-values
image dataparameterestimates
designmatrix
anatomicalreference
kernel
StatisticalParametric Map
Thresholding &Random Field
Theory
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By smoothing, data points are averaged with their neighbours.
A smoothing kernel (shape) such a Gaussian is used.
Then each value in the image is replaced with a weighted average of itself and its neighbours.
Smoothness is expressed as
FWHM (full width at half maximum)
FWHM
Gaussian curves
Standard Normal Distribution (Probability density function)Mean = 0Standard Deviation = 1
1st
Smoothing →Estimation of smoothness
For example, FWHM of 10 pixels in X axis means that at 5 pixels from the center, the value of the kernel is half of its peak value.
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Original data: an image using independent random numbers from the normal distribution
After smoothing with a Gaussian smoothing kernel FWHM in x=10, in y=10 so this FWHM=100 pixels)
1st
Smoothing →Estimation of smoothness
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The number of ressels depend on the FWHM the number of boxels (pixels).
<example of ressel>The FWHMs were 10 by 10 pixels.Thus a resel is a block of 100 pixels.As there are 10,000 pixels in our image, there are 100 resels.
Resel a block of values, e.g. pixels, that is the same size as the FWHM. a word made form ‘Resolution Elements’one of a factor which defines p value in RFT
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Smoothing
• Compiles the data of spatial correlation.
• Reduce the number of independent observations.
• Generates a blurred image.
• Increases signal-to-noise ratio.
• Enables averaging across subjects.
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2nd step Apply RFT
Euler characteristics (EC)= the number of blobs (minus number of holes) in an image after thresholding
After smoothing
Set the threshold as z core 2.5Below 2.5..0..blackAbove 2.5..1..white
EC=3
thresholding
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z=2.5 Z=2.75
Different Z score thresholdgenerates different EC.
EC=3 EC=1
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Thresholding
No of blobs≒ EC
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Expected EC: E[EC] = the probability of finding a blob
PFWE ≒ E[EC]
α = E[EC] = R (4 loge 2) (2π) -3/2 zt exp(-zt2/2)
E[EC] depends on:R the number of resels Zt Z score threshold
3rd step Obtain PFWE
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E[EC]=0.05
RFTUsing this Z score, we can conclude that any blots have a probabilityof ≦0.05 when they have occured by chance. α=E[EC]=0.05 Z=3.8
Bonferroni correction α =0.05/10,000=0.00005 Z=4.42If the assumption of RFT are met, then the RFT threshold is more accurate than the Bonferroni correction.
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RFT in 3D• EC=the number of 3D blobs• Resel=a cube of voxels of size (FWHM in x) by
(FWHM in y) by (FWHM in z)• In SPM, the formulae for t, F and χ2random fields
are used to calculate threshold for height.• RFT requires FWHM > 3 voxelsRFT requires FWHM > 3 voxels
27 Voxels 1 RESEL
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RFT Note 1:When FWHM is less than 3.2 voxels, the Bonferroni correction is better than the RFT for a Gaussian statistic.
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RFT Note2:EC depends on volume shape and size.• EC depends, not only on resel numbers,
but also on the shape and size of the volume we want to search (see table).
• The shape becomes important when we have a small or oddly shaped regions.
V: volume of search regionR0(V): ressel single boxel countR1(V): ressel radiusR2(V): ressel surface areaR3(V): ressel volume
Worsley KJ, et al. , Human Brain Mapping 1996
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Correction in case of a small shaped region
• Restricting the search region to a small volume within a statistical map can reduce thresholds for given FWE rates.
T thoreshold giving a FWE rate of 0.05.
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EC Diameter Surface AreaVolume
FWHM=20mm
Threshold depends on Search Volume
Volume of Interest:
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Note 3:voxel-level inference → a larger framework inference: different thresholding method
• Cluster-level inference
• Set-level inference
• These framework requireHeight thresholdspatial extent threshold
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Peak (voxel), cluster and set level inference
Peak level inference:height of local maxima(Special extent threshold is 0)
Cluster level inference:number of activated voxels comprising a particular region (spatial extent above u)
Set level inference:the height and volume threshold (spatial extent above u)→ number of clusters above u
Sensitivity
Regional specificity
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Which inference we should use?
• It depends on what you're looking at.
• Focal activation is well detected with greater regional specificity using voxel (peak) – level test.
• Cluster-level inference – can detect changes missed on voxel-level inference, because it uses the spaticial extent threshold as well.
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SPM8 and RFT: Example DataSPM manual, http://www.fil.ion.ucl.ac.uk/spm/doc/
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Random Field Theory: two assumptions
The error fields are a reasonable lattice approximation to an underlying random field , with a multivariate Gaussian distribution.
The error fields are continuous.
The data can be sufficiently smoothed.
The errors are indeed Gaussian and General Linear Models can be correctly specified.
RFT assumption is met.
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A case where the RFT assumption is not met.
Small number of subjects
The error fields are not very smooth.
Increase the subject numberUse Bonferroni correction
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Conclusion A large volume of imaging data
Multiple comparison problem
Bonferroni correction α=PFWE/nCorrected p value
FWE rate is too lowto reject the null hypothesis
Too false negative
Never use this.
<smoothing with a Gaussian kernel, FWHM >
Random field theory (RFT)
α = PFWE ≒ E[EC] Corrected p value
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Conclusion
• By thoresholding, expected EC is calculated by RFT, where
PFWE ≒ E[EC]• Restricting the search region to a small volume, we can
reduce the threshold for given FWE rates.• FWHM is less than 3.2 voxels, the Bonferroni correction
is better.• Voxel-level and cluster-level inference are used
depending on what we are looking at.• In case of small number of subjects, RFT is not met.
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Acknowledgement
• The topic expert: Guillaume Flandin
• The organisers: Christian LambertSuz PrejawaMaria Joao
Thank you for your attention!