1. 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

2. Cerebral blood vessels
Capillary beds extend into gray matter
Arteries enter cortical surface perpendicularly
Layer 1 - outer
Layer 6 - inner

3. Signal Pathway in BOLD fMRI
Brain activity
Glucose, O2 consumption
blood volume, blood flow
Oxyhemoglobin
Deoxyhemoglobin
Oxy – diamagnetic
(weak)
Deoxy – paramagnetic
(strong)
M = cH
(susceptibility constant = c)
Deoxy> ctissue
Oxy~ ctissue
Magnetic Susceptibility
T2*, T2
fMRI Signal

4. T2* fMRI Signal
HbO2 – Oxyhemoglobin
Hbr - Deoxyhemoglobin

5. From Neural Activity to fMRI Signal
Signalling
Vascular response
Vascular tone (reactivity)
Autoregulation
Metabolic signalling
BOLD signal
glia
arteriole
venule
B0 field
Synaptic signalling
Blood flow,
oxygenation
and volume
End bouton
dendrite
Complex relationship between change in neural activity and change in blood flow (CBF), oxygen consumption (CMRO2) and volume (CBV).

6. 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

7. 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
Visual cortex Monkey
Rotating checkerboard
Logothetis et al, Nature 2001

8. Haemodynamic Response
balloon model
Functional contrast (and what each is good for)
BOLD (blood oxygenation level dependent)
T2 and T2*
Perfusion (arterial spin labelling) - more quantitative but lower SNR
Cerebral blood volume
VASO, vascular space occupancy
Functional Spectroscopy % -1
initial dip
undershoot
Buxton R et al. Neuroimage 2004

9. fMRI Bold Response Model
time
BOLD response, %
initial
dip
positive
BOLD response
post stimulus
undershoot
overshoot 1 2 3
stimulus
Initial dip 0.5-1sec
Overshoot peak 5-8 sec
+ BOLD response 2-3%
Final undershoot variable
Deoxyhemoglobin
BOLD signal
Figure 8.1. from textbook.

10. A BOLD Block Design Visual Study
stimulus
off on
image
acquisition
time
time
voxel response -2 2 6 14 10
t value
4.5 3
Signal [%]
correlation
1.5
predicted
response
-1.5 20 40 60 80
100
120
140
160
180
Time [s]
Bruce Pike, BIC at MNI.

11. 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 that are long relative to BOLD response.

12. 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 %.
Figure 8.2. from textbook. N=12 subjects.

13. Model of Overshoot/Undershoot
Models of waveform for a) BOLD and b) perfusion (CBF) change.
Constant stimulation 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.

14. Perfusion vs. Volume Change
30 second stimulation
3-second intervals
DCBF rapid
DCBV slow
In rat experiments TC for DCBV similar to that for BOLD overshoot.
Figure 8.4. from textbook.
Mandeville et al., 1999

15. Measurement of Cerebral Blood Flow with PET or MRI (Arterial Spin Labeling - ASL)+
511 keV
PET
Method
O-15 H20
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

16. Arterial Spin Labeling
z (=B0)
inversion
slab
imaging
plane
excitation
blood y x
inversion
white matter = low perfusion
Gray matter = high perfusion
ASL IMAGE = IMAGEunlabeled – IMAGElabeled
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

17. Hypercapnia, Perfusion, & BOLD Responses
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.

18. Relative BOLD vs. Relative CBF
M is max possible BOLD signal change
a is CBV-CBF coupling constant (0.38 for graphs)
b is deoxy attenuating power (1.5 for graphs)
Figure 8.6. from textbook.

19. ASL interleaved with BOLD
Acquisition of CBF and BOLD data supports calculation of CMRO2 using model equation.
Figure 8.8. from textbook.

20. 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.

21. 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 from textbook.

22. Localization of Functional Contrast
Perfusion
Perfusion Activation
draining
vein
BOLD Activation
BOLD*
*1.5T/Gradient Echo

23. Group (Random Effects)
ASL Perfusion fMRI vs. BOLD Improved Intersubject Variability vs. BOLD Aguirre et al., NeuroImage 2002
Group (Random Effects)
Single Subject

24. Physiological Basis of fMRI
behavior
neural function
disease
biophysics***
metabolism
BOLD fMRI
ASL CBF MRI
***BOLD contrast includes contributions from biophysical effects such as magnetic field strength homogeneity and orientation of vascular structures.
blood flow
ASL fMRI measures changes in CBF directly, and hence measured signal changes may be more directly coupled to neural activity