10/1/2012

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ssss s
Xin Di, PhD
Suril Gohel
UMDNJ-New Jersey Medical school
Contents
ü An example data - by Dr. Yu-Feng Zang
· Resting-state: eye open vs. eye close
ü Data analysis
ü Prepare Data for analysis
· Preprocessing
ü Device and Employ methods to Test hypothesis
· Local properties
· Connectivity
ü Test the Hypothesis and Ìnfer Results
· Group inference
ExampIe data set
ü Eye open/Eye closed data from ÌNDÌ
(http://fcon_1000.projects.nitrc.org/indi/retro/BeijingEOEC.html)
ü 24 Subjects
ü Eye open, 6min, 240 images
ü Eye close, 6min, 240 images
ü TR 2 second, Voxel size: 3.1×3.1×3.5 mm
ü Anatomical SPGR image (MPRAGE Ìmage)
Specific to resting-state fMRÌ
Similar to task fMRÌ
Generally is not needed
Image preprocessing
ü Slice timing
ü Motion correction
ü Spatial processing
· Spatial normalization
· Spatial smoothing
ü Temporal processing
· Noise removal
· Filtering
· Global Ìntensity
normalization/Global
Regression
TemporaI processing
ü Noise removal
· Physiological noises
· Head motion
ü Filtering
· Usually 0.01 ÷ 0.08 Hz
ü Global Ìntensity
normalization/Global
regression
· Physiological noises
o Cardiac
o Respiratory
TemporaI processing
ü Noise removal
· Physiological noises
· Head motion
ü Filtering
· Usually 0.01 ÷ 0.08 Hz
ü Global Ìntensity
normalization/Global
regression
WM/CSF Signal
o High probability threshold
p > 0.99 not p > 0.5
o Use eroded WM/CSF masks
o Use unsmoothed fMRÌ data
o Mean time course or principle
components (Chai et al., 2012)
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TemporaI processing
ü Noise removal
Physiological noises
Head motion
ü Filtering
Usually 0.01 ÷ 0.08 Hz
ü Global Ìntensity
normalization/Global
regression
· Head motion
o Six rigid-body motion
parameters (translation and
rotation)
o Or their derivatives??
TemporaI processing
ü Noise removal
Physiological noises
Head motion
ü Filtering
Usually 0.01 ÷ 0.08 Hz
ü Global Ìntensity
normalization/Global
regression
· Global Ìntensity
normalization/Global
Regression
Will introduce negative
correlations (Murphy et al.,
2009)
NEVER!
Time series preprocessing
0 50 100 150 200 250 1030
1035
1040
1045
1050
1055
0 50 100 150 200 250 -8
-6
-4
-2
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0 50 100 150 200 250 -6
-4
-2
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6
0 50 100 150 200 250
-800
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-200
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800
0 50 100 150 200 250
-300
-200
-100
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300
0 50 100 150 200 250
-0.5
-0.4
-0.3
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0.1
0.2
Raw time course Regress out covariates Band-pass filtering
First 5 PCs of WM First 5 PCs of CSF Motion parameters
Hypothesis
ü Experiment
· Eye open vs. Eye close
ü Goal
ü Functional specification
· Local properties
ü Functional integration
· Connectivity
LocaI properties
ü Time-domain Properties
· Standard deviation (Biswal et al., 2007)
ü Frequency-domain Properties
· Amplitude of Low-Frequency Fluctuation (ALFF, Zang et al.,
2007)
· Fractional Amplitude of Low-Frequency Fluctuation (fALFF, Zou
et al., 2008)
ü Homogenous Properties
· Regional Homogeneity (ReHo, Zang et al., 2004)
ü Fractal Properties
· Hurst exponent (Bullmore et al., 2004)
Measuring IocaI properties
ü ALFF (Zang et al., 2007)
· Band-Pass Filtering
· Fourier transform
· Square root
· Average across 0.01 - 0.08
Hz - ALFF
· Divided by global mean ÷
mALFF
· Divided by whole spectrum -
fALFF (Zou et al., 2008)
Zang et al., 2007
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Measuring IocaI properties
ü ReHo (Zang et al., 2004)
· Local similarity
· Kendall's coefficient of
concordance (KCC)
==
( R
i
)
2
~ n( R)
2
1
12
K
2
( n
3
~ n)
7 19 27
CaIcuIating ALFF/fALFF/ReHo
ü Detrend
ü Ìdeal temporal filtering
(0.01-0.08 Hz)
ü Calculating
· ALFF/mALFF
· fALFF/mfALFF
· ReHo/mReHo
Resting-State fMRÌ Data Analysis
Toolkit (http://www.restfmri.net/)
mfALFF
mReHo
mALFF
SingIe subject maps
Eye open Eye close
Group inference
ü Whether the effects are
reliable across subject?
ü Whether the effects are
different between two
groups?
ü Whether the effects are
different between
conditions?
ü More than two
groups/conditions
One-sample t-test
Two-sample t-test
Paired t-test
(repeated measure) ANOVA
Group inference
ü Group differences
ü Covariates
ü Global scaling
ü Mask (absolute mask or
whole brain mask)
Design matrix
Groups Effects of no interest
Group inference
ü Within-subject effects
ü Covariates
ü Global scaling
ü Mask (absolute mask or
whole brain mask)
Design matrix
Conditions Subjects
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eye close
> eye open
eye open
> eye close
Group inference
mALFF mfALFF mReHo
p < 0.001, cluster level FDR p < 0.05
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p < 0.001
k > 10
Measuring connectivity
ü Functional connectivity
· Correlation
· Mutual information
ü Effective connectivity
· Granger causality
· Dynamic causal model
A B
A B
Measuring connectivity
ü ROÌ-based analysis
· Simple
· Need strong hypothesis
· Selectivity problem
?
Measuring connectivity
ü Seed-based correlation
· Less strong hypothesis
· Exploratory
· Specificity
· Correlation maps might be
affected by seed selection
?
Measuring connectivity
ü Spatial independent
component analysis (ÌCA)
· Pure data-driven
· Complicated algorithm
· Explaining the results with
caution
Seed-based correIation
ü Defining ROÌs
· Local differences (ALFF differences.)
· Structural (AAL, Brodmann's area.)
· Previous study (Coordinates)
· Meta-analysis (Activation likelihood estimation .)
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Seed-based correIation
ü Covariates
· Motion parameters
(translation, rotation,
derivatives...)
· White matter, CSF (mean,
PCA princomp)
· Global signal (NEVER!)
· High-pass filter (1/100 Hz)
· Series correlation (AR(1)?)
Design matrix
Seed WM CSF Motion Constant
Left
Visual
Seed-based correIation
Right
Visual
PCC
Seed
Eye open Eye close
Single subject maps
eye close
> eye open
eye open
> eye close
Seed-based correIation
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L. visual seed R. visual seed PCC seed
p < 0.001, cluster level FDR p < 0.05
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Group level analysis
SpatiaI ICA
ü Melodic in FSL
ü GÌFT in MATLAB
ü Ìssues
· Run ÌCA together or
separately?
· Number of components?
Cole et al., 2010
Left
Executive
Motor
Higher
Visual
Right
Executive
DMN 1
st
Visual
IC maps aItogether
Primary
visual ÌC
IndividuaI IC Maps
Higher
visual ÌC
DMN ÌC
Eye open Eye close
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eye close
> eye open
eye open
> eye close
Condition differences
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1
st
Visual ÌC Higher Visual ÌC DMN ÌC
p < 0.001, cluster level FDR p < 0.05
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ResuIts summary
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Convergent results in higher visual area
Higher ALFF Higher ReHo
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Higher connectivity
with right visual ROÌ
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Primary Visual
ÌC activity
Summary remarks
ü Design is simple. Analysis is flexible.
· Take care of physiological noises
· Reporting analysis procedures in detail
ü Be careful when using global signal regression
ü Take care of multiple comparison problem
· Not only multiple voxels, but also multiple ÌCs, and multiple
seeds.
References
ü ALFF: Zang YF, He Y, Zhu CZ, Cao QJ, Sui MQ, Liang M, Tian LX, Jiang TZ, Wang YF, (2007).
Altered baseline brain activity in children with ADHD revealed by resting-state functional MRÌ.
Brain Dev 29(2):83-91.
ü fALFF: Zou QH, Zhu CZ, Yang Y, Zuo XN, Long XY, Cao QJ, Wang YF, Zang YF, (2008). An
improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state
fMRÌ: fractional ALFF. J Neurosci Methods172(1):137-41.
ü Reho: Zang Y, Jiang T, Lu Y, He Y, Tian L, (2004). Regional homogeneity approach to fMRÌ data
analysis. Neuroimage22(1):394-400.
ü Seed-based correlation: Biswal B, Yetkin FZ, Haughton VM, Hyde JS, (1995). Functional
connectivity in the motor cortex of resting human brain using echo-planar MRÌ. Magn Reson
Med34(4):537-41.
ü Seed-based correlation: Cordes D, Haughton VM, Arfanakis K, Wendt GJ, Turski PA, Moritz CH,
Quigley MA, Meyerand ME, (2000). Mapping functionally related regions of brain with functional
connectivity MR imaging. AJNR Am J Neuroradiol 21(9):1636-44.
ü ÌCA: Beckmann CF, DeLuca M, Devlin JT, Smith SM, (2005). Ìnvestigations into resting-state
connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci
360(1457):1001-13.

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