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Global brain physiology
does not impact regional
BOLD activations
Yufen Jennie Chen
Xue Wang
Todd B. Parrish
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Disclosure
The authors have no relevant financial interest or relationship to
disclose with regard to the subject matter of this presentation.
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Purpose
 Blood-oxygenation level dependent (BOLD) fMRI is a
complex interplay between multiple physiological
processes including cerebral blood flow, cerebral blood
volume, oxygen consumption and neural activity.
 Intersubject variability in baseline local CBF accounts for
variability in BOLD response to tasks1
 Recently developed MRI techniques can quantitatively
measure global cerebral metabolic rate of oxygen
(CMRO2)2
The purpose of this study is to investigate whether
global CMRO2 will affect the amplitude of task-related
BOLD response
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
Materials & Methods
Subjects
 Group 1: 9 subjects (4F, 36 ± 9 years old)
 Group 2: 8 subjects (4F, 29 ± 4 years old)
Tasks
 Synonyms task (group 1): alternating 30s epochs
of word pairs and letter strings, repeated 8 times
(scan time: 8’06”)
 Story comprehension (group 2): alternating 24s
epochs of stories and scrambled words,
repeated 8 times (scan time: 6’30”)
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Materials & Methods
Imaging
 3.0T Siemens TIM Trio & 32 channel head coil
 BOLD fMRI: gradient-echo echo planar imaging
(EPI)
 Group 1: 1.7x1.7x3mm3, TE=20ms, TR=2s, 35 slices
 Group 2: 1.7x1.7x3mm3, TE=20ms, TR=2.4s, 42 slices
 Venous oxygenation: postsat-TRUST3
 1.4x1.4x5mm3, TE=18ms, TR=4s, TEeff=0/40/80/160 ms, 1 slice through
sagittal sinus
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Materials & Methods
Imaging (Cont.)
 Global blood flow: retro-gated phased contrast
MRI (PC-MRI)
 0.5x0.5x5mm3, Venc=80cm/s, 20 phases, TE=3.81ms,
TR=66.3ms, 1 slice positioned perpendicular to carotids
and vertebrals based on non-contrast time-of-flight scan
 Multiple scans were run to ensure perpendicular crosssection for all major arteries
Sample position planning of scan for carotids
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
Materials & Methods
 BOLD analysis
 Preprocessing: coregistration, motion correction,
smoothing (6mm), non-linear spatial normalization
1
to MNI152_T1 template
 First-level GLM analysis for each subject
 Preprocessing and first-level analysis performed
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via online pipeline4
 Second-level GLM analysis on the contrast
images of the group
Location of ROIs
 % signal change extracted from two ROIs using
MarsBar5
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Materials & Methods
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Data analysis for TRUST
 Coregistration between TEeff data
and motion-correction within TEeff
data
 pairwise subtraction between control
& tag images
 Extract mean signal of 6 highest
signal voxels in sagittal sinus
 Fit for blood T2 and Yv3
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
Example of data & fit
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Materials & Methods
Data analysis for PC-MRI
 Calculate total CBF by summation of flow in bilateral
carotids and vertebral arteries, average over cardiac
cycle
 Estimate brain volume from tissue segmentation of
high resolution anatomical T1
 Calculate normalized CBF per tissue mass
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
Materials & Methods
CMRO2 calculation
 CMRO2 = CBF * (Ya-Yv) * Ca
 Ya = arterial oxygenation ~ 100%
 Yv = venous oxygenation (calculated from TRUST)
 Ca = amount of oxygen/volume of blood = 8.337
mol O2/ml of blood
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Results: Correlations with physiology
Total flow is positively correlated with both venous oxygenation (Yv)
and cerebral metabolic rate of oxygen (CMRO2)
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Results: Correlations with %BOLD
ROI1
r
CBF
(ml/100g/min)
ROI2
p
r
p
0.33
0.38
0.14
0.71
0.35
0.36
0.22
0.57
CMRO2
(mol/100g/min)
0.26
0.50
0.10
0.79
CBF
(ml/100g/min)
0.03
0.94
0.15
0.72
0.02
0.97
0.28
0.51
0.14
0.74 -0.37
0.36
Group 1 Yv (%)
Group 2 Yv (%)
CMRO2
(mol/100g/min)
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Conclusion
Global CBF is positively correlated with venous
oxygenation and oxygen consumption
None of the physiological metrics correlated with
%BOLD
 Global physiology is preserved in spite of local
disturbances such as functional activation
 Current CMRO2 technique is a static measure, which
may not be sensitive to local dynamic changes queried
by BOLD
 Balance in global physiology may be disrupted with
aging and disease of the neurovascular system
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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Future Work
Implement technique for local physiological
metrics to better understand their effects on
functional activity
Extend findings in older healthy controls
and chronic stroke patients
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20
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References
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Liau J., Liu TT. Inter-subject variability in hypercapnic normalization
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Xu F., Ge Y., Lu H. Noninvasive Quantification of Whole-Brain
Cerebral Metabolic Rate of Oxygen (CMRO2) by MRI. Magn Reson
Med 62 (2009) 141–148
Xu F., Uh J., Liu P., Lu H. On Improving the Speed and Reliability of
T2-Relaxation-Under-Spin-Tagging (TRUST) MRI. Magn Reson Med
68 (2012) 198–204
Song X., et al. Robust web-based parallel-optimized minimal
preprocessing and analysis pipeline for fMRI big data. OHBM 2015,
Honolulu, Hawaii
Brett M., et al. Region of interest analysis using an SPM toolbox.
OHBM 2002, Sendai, Japan
53rd ASNR meeting 2015, Chicago IL
Poster #:EP-20