Transcript Estimating Oxygen Saturation of Blood in Vivo with MR

BOLD Contrast:
Functional Imaging with MRI
Mark A. Elliott, PhD
Department of Radiology
University of Pennsylvania
Overview
1.
2.
3.
4.
Mechanisms of functional imaging with MRI
Methodology of fMRI
Issues for animal studies
Spatial and temporal sensitivy of fMRI
Methods for Imaging Neural Activity
metabolic response
electrical activity
- excitatory
- inhibitory
- soma action potential
electrophysiology
EEG
MEG
- ATP tightly regulated
- glucose consumption
- oxygen consumption
FDG PET
H215O PET
hemodynamic response
- blood flow
- blood volume
- blood oxygenation
fNIR
fMRI
Perfusion MRI
Vascular Sensitivity of
fMRI and fNIR
Arterial
Venous
II
Intravascular
fNIR
I
Perfusion MRI
II
fMRI
III
Extravascular
III
IV
Vessel Size
IV
I
Vascular Response
fMRI vs fNIR
fMRI
Spatial Resolution
8-27 mm3
Temporal Resolution
Slow (1-2 sec)
Measurement parameter
Mix of blood volume, blood
flow, and O2 metabolism
fNIR
“Blobs”
1-10 cm3
Fast (50 Hz)
important?
[Hb] and [HbO]
Mechanisms of fMRI Signal:
BOLD Contrast
Neural Activity
CMR02
“Flooding the garden to feed
the thirsty flower” - ???
CBF
spatial dimension
BOLD ( CBF - CMR02)
• Hemodynamic response is a surrogate marker for neural activity
• BOLD = Blood Oxygenation Level-Dependent
• BOLD signal is a complex interaction of CBF + CBV + CMRO2:
– CBF >> CMRO2  less deoxyhemoglobin with activation
– CBF is monitored indirectly
– “Tracer” is primarily venous
– “Tracer” is endogenous
Magnetic Susceptibility Affects
Background Magnetic Field
: permeability
r : relative permeability
M: magnetic susceptibility
B  H
  r 0
r 1  M
For biological tissues, | M | << 1
Diagmagnetic: M < 0
Paramagnetic: M > 0
The interface between regions with
different M behaves like a magnetized
dipole, perturbing the local B field.
B1  B2
M1 B1
B2
M2
 M creates larger B
BOLD Contrast: Changes in
Magnetic Susceptibility of Blood
Blood and brain tissue are diamagnetic.
Hb0 is diamagnetic.
Hb is strongly paramagnetic.
HbO is paramagnetic.
Increased Neuronal activity:
• blood flow increases ≈ 30%
• 02 consumption increases ≈ 5%
• [Hb0] 
• [Hb] 
Decrease in [Hb] reduces the M between blood and brain tissue
Magnetic field becomes more uniform  MRI signal affected
Hemoglobin Saturation Affects
Magnetic Field Homogeniety
from Ogawa, 1990
Rat brain, 7T
Field Map vs. Hemoglobin Saturation
from Bandettini and Wong, 1995
Normoxia
Hypoxia
Summary: BOLD Contrast in fMRI
Verbal Fluency Task
Broca’s area
Wernicke’s area
• BOLD = Blood Oxygenation Level-Dependent
• Oversupply of CBF raises [HbO] in regions of increased CMRO2
• Susceptibility mismatch between blood and tissue is reduced
• Magnetic field becomes more homogeneous
• Temporal T2* contrast generated in T2* sensitive MRI
fMRI Methodology: Acqusition
structural
T1 weighted
~ 5 min
1x1x1 mm voxels
Temporal series of EPIs
....
EPI
functional
T2* weighted
~ 2 sec/volume
3x3x3 mm voxels
~ 300 images
~ 10 min
time
fMRI Methodology: Stimulus
Blocked Design, Event-Related Design, and ISI
ISI
On
Fixed ISI
Blocked Design
Off
On
Event Related
Off
Event related designs can have either fixed or variable inter-stimulus interval (ISI)
ISI
Variable ISI allows for more stimuli per time.
• Increased statistical power in analysis.
Variable ISI
fMRI Methodology: Analysis
“Non-Activation”
Signal
Stimulus
....
Processing
“Activation”
Processing
Signal
Stimulus
Brain Activation Maps
Statistical Parametric Mapping
T2*-weighted
Snapshot
Image
Average
Difference
Image
Statistical
Significance
Image
Thresholded
Statistical
Image
Overlay on
Anatomic
Image
ON
OFF
task
signal
courtesy J. Detre
Hemodynamic Response Function
The “HRF” the theoretical impulse response of BOLD contrast to brief neuronal activity
PeakAmplitude
Contrast
FWHM
Onset Time
Stimulus
Time to Peak
fMRI Model: HRF Linear System
Linear Model Assumption
y=hx
stimulus (x)
HRF (h)
Expected signal (y) is convolution of the
stimulus signal (x) with the HRF (h)
Signal is predicted for any arbitrary sequence of stimuli
signal (y)
Applications of fMRI
• Cognitive Neuroscience
– Localization of sensorimotor and cognitive function
– Brain-behavior correlations
• Clinical Neuroscience
– Presurgical mapping
– Differential diagnosis of cognitive disorders
– Recovery of function/neuroplasticity
Photic Stimulation
Implications for Animal fMRI
• Pharmacological effects on neuronal metabolism and hemodynamic
response
• Small voxel sizes reduce SNR
• Smaller volumes enable higher field magnets (7 and 9.4T)
• Passive stimulus delivery (training possible in some models)
T2* Signal Loss in the Pre-Frontal Cortex
F
Air is highly paramagnetic (like Hb)
Air-tissue interface has “static” M
Background signal “drop-out”
B0
S
E
1
B0
2
Bn = Normal component
F = frontal sinus
E = ethmoidal sinus
S = sphenoidal sinus
Bn = Tangential component
Normal component is unchanged by 
B1n = B2n
Tangential component is altered by 
B1n = 1 / 2 B2n
Signal Dropout in
T2* Weighted Images
TE=4ms
TE=12ms
TE=20ms
TE=28ms
TE=36ms
TE=44ms
TE=52ms
Increasing TE
TE=60ms
Spatial Extent of BOLD
Neural Activity
CMR02
CBF
BOLD ( CBF - CMR02)
draining veins
Hb Saturation (%, approx.)
resting active
arterioles 90
90
capillaries 80
90
veins
60
90
microvessels
Positive T2* contrast derived from CBF > CMR02
Venous compartment experiences largest Hb (and T2*)
Draining veins are less spatially specific to site of neural activity
Extravascular BOLD Signal
B0 “inhomogeneity” from vessel extends into extravascular (EV) space
EV Magnetic Field Gradient
microvessel
macrovessel
Diffusion of water molecules through B0 gradients
• Large vessels: static dephasing, T2* effect
• Small vessels: dynamic dephasing, T2 and T2* effect
Spin-echo fMRI less sensitive to large vessel (venous)
extravascular space
water diffusion
from Principles of Functional MRI, Seong-Gi Kim
Echo Time and Field Strength
Effects on BOLD Contrast
• BOLD contrast increase with echo time (TE)
• SNR decreases with echo time
• Optimal CNR when TE  resting T2*
• BOLD contrast increases with magnetic field
• SNR increases with magnetic field
% Signal
1.5T
% Signal
TE (msec)
3T
TE (msec)
from Stroman et al, Proc. ISMRM, Glasgow (2001)
Field Strength Effect
on BOLD Spatial Sensitivity
• T2* of blood shortens quadratically with B0
• Field dependence of T2,blood  T2,tissue
- Decreased venous contribution
Diffusion weighted BOLD
Rat brain, 9.4T
Intravascular BOLD component
model simulation
from S.P. Lee et al, (2003)