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Statistical Parametric
Mapping
Lecture 2 - Chapter 8
Quantitative Measurements Using fMRI
BOLD, CBF, CMRO2
Textbook: Functional MRI an introduction to methods, Peter Jezzard,
Paul Matthews, and Stephen Smith
Many thanks to those that share their MRI slides online
Cerebral
blood vessels
Layer 1
Layer 6
• Capillary beds
extend into gray
matter
• Arteries enter
cortical surface
perpendicularly
Neuron’s General Structure
~50,000 neurons per cubic mm
~6,000 synapses per neuron
~10 billion neurons & ~60 trillion synapses in cortex
• input - dendrites & soma
• processing - throughout
• output - axon
Structural variety of neurons
Signal Pathway in BOLD fMRI
Brain activity
Glucose, O2 consumption
blood volume, blood flow
Oxyhemoglobin
Deoxyhemoglobin
Oxy – diamagnetic
Deoxy – paramagnetic
Magnetic Susceptibility
T2*, T2
fMRI Signal
M = cH
(susceptibility
constant = c)
cDeoxy> ctissue
cOxy~ ctissue
T2* fMRI Signal
HbO2 – Oxyhemoglobin
Hbr - Deoxyhemoglobin
From Neural Activity to fMRI Signal
Neural activity
Signalling
Vascular response
Vascular tone (reactivity)
Autoregulation
Synaptic signalling
BOLD signal
Blood flow,
oxygenation
and volume
arteriole
B0 field
glia
Metabolic signalling
End bouton
dendrite
venule
Complex relationship between change in neural activity and change in
blood flow (CBF), oxygen consumption (CMRO2) and volume (CBV).
fMRI and Electrophysiology
LFP – local field
potentials reflect
dendritic currents
MUA – multiunit activity
SDF – single unit
activity (?)
a. 24 sec stimulation
b. 12 sec stimulation
c. 4 sec stimulation
Logothetis et al, Nature
2001
Haemodynamic Response
balloon model
%
-1
Buxton R et al. Neuroimage 2004
initial dip
undershoot
fMRI Bold Response Model
positive
BOLD response
•
•
•
•
Initial dip
0.5-1sec
Overshoot
peak 5-8 sec
+ BOLD response
2-3%
Final undershoot
variable
3
BOLD response, %
2
initial
dip
overshoot
post stimulus
undershoot
1
Deoxyhemoglobin
BOLD signal
0
time
stimulus
Figure 8.1. from textbook.
A BOLD Block Design
Visual Study
on
stimulus
off
time
image
acquisition
time
voxel response
14
4.5
6
correlation
2
0
Signal [%]
10
3
predicted
response
1.5
0
-2
t value
-1.5
0
Bruce Pike, BIC at MNI.
20 40 60 80 100 120 140 160 180
Time [s]
Non-Linearity of BOLD Response
BOLD response vs. length of stimulation
t
2t
BOLD response during rapidly-repeated stimulation
ts
Block designs use stimulus and rest periods are that are
long relative to BOLD response.
Graded BOLD Response
• Graded change in signal for a) BOLD and b) perfusion (CBF).
• 3 minute visual pattern stimulation with different luminance levels.
• Note max BOLD change of 2-3 % and max CBF change of 40-50 %.
Figure 8.2. from textbook. N=12 subjects.
Model of Overshoot/Undershoot
• Models of waveform for a) BOLD and b) perfusion (CBF) change.
• Constant stimulation 50-250 sec.
• Overshoot more pronounced in BOLD waveform
• slow adjustment of CBV (Mandeville et al., 1999)
• Undershoot might be due to same effect
Figure 8.3. from textbook.
Perfusion vs. Volume Change
•
•
•
•
30 second stimulation
3-second intervals
CBF rapid
CBV slow
In rat experiments TC for CBV similar to that for BOLD overshoot.
Figure 8.4. from textbook.
Mandeville et al., 1999
Measurement of Cerebral Blood Flow
with PET or MRI (Arterial Spin Labeling - ASL)
PET orPET
SPECT
arterial
labeling
MRI PERFUSION
Steady State Method
Steady State Method
Method
keV
 511
decay
imaging
slice
control
labeling
T1 relaxation
+
511 keV
arterial
spin labeling
15 O infusion
O-15 H 0
2
or inhalation
• Uses magnetically labeled arterial blood water
as an endogenous flow tracer
• Potentially provide quantifiable CBF in
classical units (mL/min per 100 gm of tissue)
Detre et al., 1992
Arterial Spin Labeling
z (=B0)
excitation
y
inversion
slab
blood
x
inversion
imaging
plane
• ASL IMAGE = IMAGEunlabeled – IMAGElabeled
•
•
•
•
white matter = low
perfusion
Gray matter = high
perfusion
Mostly use inversion (IR) labeling
Labeled blood water extracted from capillaries
T1 of blood is long compared to tissues
Flow (perfusion) not dependent on local susceptibility
www.fmrib.ox.ac.uk/~karla/
Hypercapnia, Perfusion, & BOLDResponses
CMRO2 – Cerebral Metabolic Rate of Oxygen Consumption
Hypercapnia (increased CO2) increases CBF w/o increasing oxygen demand (CMRO2).
• Response with graded hypercapnia (GHC thin line) and graded visual
stimulation (GVS). Four levels in this study.
• BOLD response similar to CBF response to hypercapnia
• BOLD response attenuated relative to CBF during aerobic stimulation
Figure 8.5. from textbook. Perfusion (CBF) and BOLD changes.
ASL interleaved with BOLD
Acquisition of CBF and
BOLD data supports
calculation of CMRO2 using
model equation.
1/ 
CMRO2  BOLD / BOLD 0 
 1 

CMRO2,0 
M

Figure 8.8. from textbook.
1 / 
 CBF 


CBF

0 
Flow/Metabolism Coupling and
the BOLD Signal
•
•
BOLD vs Perfusion (CBF)
• graded hypercapnia (dark circles)
• graded visual stimuli (different shapes)
CMRO2 vs Perfusion (CBF)
• perfusion has somewhat linear relationship with CMRO2
• derived from data in “a”
Figure 8.9. from textbook.
Model Based Images
a. M from model equation – predicts max BOLD signal potential
b. BOLD – visual stimulation flashing checkerboard
c. CBF (perfusion)
d. CMRO2 (oxygen compution rate)
Figure 8.10. from textbook.
Localization of Functional
Contrast
Perfusion
Perfusion Activation
BOLD*
*1.5T/Gradient Echo
BOLD Activation
draining
vein
ASL Perfusion fMRI vs. BOLD
Improved Intersubject Variability vs. BOLD
Aguirre et al., NeuroImage 2002
Single Subject
Group (Random Effects)
Physiological Basis of fMRI
behavior
neural function
disease
biophysics***
metabolism
BOLD fMRI
***BOLD contrast includes
contributions from biophysical
effects such as magnetic field
strength homogeneity and
orientation of vascular structures.
ASL CBF MRI
blood flow
ASL fMRI measures changes in CBF
directly, and hence measured signal
changes may be more directly coupled
to neural activity