Basics of fMRI and the BOLD Response

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Basics of fMRI and the BOLD Response

• Jody Culham
• University of Western Ontario
• London, Ontario Canada

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fMRI Setup
3
The Briefest Possible Explanation of MR Physics I
Could Manage(while still covering important
ideas and jargon)
4
Necessary Equipment
4T magnet
RF Coil
gradient coil (inside)
Magnet
Gradient Coil
RF Coil
Source for Photos Joe Gati
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The Big Magnet
Very strong 1 Tesla (T) 10,000 Gauss Earths
magnetic field 0.5 Gauss 4 Tesla 4 x 10,000 ?
0.5 80,000X Earths magnetic field Continuously
on Main field B0
Robarts Research Institute 4T
x 80,000
Source www.spacedaily.com
6
Metal is a Problem!
Source www.howstuffworks.com
Source http//www.simplyphysics.com/ flying_objec
ts.html
Large ferromagnetic objects that were reported
as having been drawn into the MR equipment
include a defibrillator, a wheelchair, a
respirator, ankle weights, an IV pole, a tool
box, sand bags containing metal filings, a vacuum
cleaner, and mop buckets. -Chaljub et al.,
(2001) AJR
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Step 1 Put Subject in Big Magnet
Protons (hydrogen atoms) have spins (like
tops). They have an orientation and a frequency.
When you put a material (like your subject) in an
MRI scanner, some of the protons become oriented
with the magnetic field.
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Step 2 Apply Radio Waves
When you apply radio waves (RF pulse) at the
appropriate frequency, you can change the
orientation of the spins as the protons absorb
energy.
After you turn off the radio waves, as the
protons return to their original orientations,
they emit energy in the form of radio waves.
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Step 3 Measure Radio Waves
T1 measures how quickly the protons realign with
the main magnetic field
T2 measures how quickly the protons give off
energy as they recover to equilibrium
fat has high signal ? bright
fat has low signal ? dark
CSF has high signal ? bright
CSF has low signal ? dark
T1-WEIGHTED ANATOMICAL IMAGE
T2-WEIGHTED ANATOMICAL IMAGE
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Jargon Watch

• T1 the most common type of anatomical image
• T2 another type of anatomical image
• TR repetition time one timing parameter
• TE time to echo another timing parameter
• flip angle how much you tilt the protons (90
  degrees in example above)

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Step 4 Use Gradients to Encode Space
field strength
space
lower magnetic field lower frequencies
higher magnetic field higher frequencies
Remember that radio waves have to be the right
frequency to excite protons. The frequency is
proportional to the strength of the magnetic
field. If we create gradients of magnetic
fields, different frequencies will affect protons
in different parts of space.
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Step 5 Convert Frequencies to Brain Space
k-space contains information about frequencies in
image
We want to see brains, not frequencies
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A Walk Through K-space
single shot spiral
two shot spiral
single shot EPI
two shot EPI
(forgive the hand drawn spirals)
Note The above is k-space, not slices

• echo-planar imaging
• sample k-space in a linear zig-zag trajectory
• spiral imaging
• sample k-space in a spiral trajectory
• single shot imaging
• sample k-space with one trajectory
• multi-shot imaging
• sample k-space with multiple (typically 2 or 4)
  trajectories
• Our technicians at RRI prefer spiral and
  multishot acquisitions because theyre more
  efficient

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Susceptibility Artifacts
T1-weighted image
T2-weighted image

• -In addition to T1 and T2 images, there is a
  third kind, called T2 tee-two-star
• -In T2 images, artifacts occur near junctions
  between air and tissue
• sinuses, ear canals
• In some ways this sucks, but in one way, its
  fabulous

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Deoxygenated Blood ? Signal Loss

• Oxygenated blood?
• No signal loss

Deoxygenated blood? Signal loss!!!
Images from Huettel, Song McCarthy, 2004,
Functional Magnetic Resonance Imaging
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Hemoglobin
Figure Source, Huettel, Song McCarthy, 2004,
Functional Magnetic Resonance Imaging
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BOLD Time Course
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Neurons ? BOLD
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Stimulus to BOLD
Source Arthurs Boniface, 2002, Trends in
Neurosciences
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Vasculature
Source Menon Kim, TICS
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Macro- vs. micro- vasculature

• Macrovasculaturevessels gt 25 ?m
  radius(cortical and pial veins)? linear and
  oriented? cause both magnitude and phase changes
• Microvasculaturevessels lt 25 ?m
  radius(venuoles and capillaries) ? randomly
  oriented? cause only magnitude changes

Capillary beds within the cortex.
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Neuron ? BOLD?
Raichle, 2001, Nature
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Neural Networks
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Post-Synaptic Potentials

• The inputs to a neuron (post-synaptic potentials)
  increase (excitatory PSPs) or decrease
  (inhibitory PSPs) the membrane voltage
• If the summed PSPs at the axon hillock push the
  voltage above the threshold, the neuron will fire
  an action potential

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Even Simple Circuits Arent Simple
gray matter(dendrites, cell bodies synapses)
Lower tier area (e.g., thalamus)
white matter (axons)

• Will BOLD activation from the blue voxel reflect
  
• output of the black neuron (action potentials)?
• excitatory input (green synapses)?
• inhibitory input (red synapses)?
• inputs from the same layer (which constitute
  80 of synapses)?
• feedforward projections (from lower-tier areas)?
• feedback projections (from higher-tier areas)?

Middle tier area (e.g., V1, primary visual
cortex)
Higher tier area (e.g., V2, secondary visual
cortex)

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BOLD Correlations

• Local Field Potentials (LFP)
• reflect post-synaptic potentials
• similar to what EEG (ERPs) and MEG measure
• Multi-Unit Activity (MUA)
• reflects action potentials
• similar to what most electrophysiology measures
• Logothetis et al. (2001)
• combined BOLD fMRI and electrophysiological
  recordings
• found that BOLD activity is more closely related
  to LFPs than MUA

Source Logothetis et al., 2001, Nature
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Comparing Electrophysiolgy and BOLD
Data Source Disbrow et al., 2000, PNAS Figure
Source, Huettel, Song McCarthy, Functional
Magnetic Resonance Imaging
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fMRI Measures the Population Activity

• population activity depends on
• how active the neurons are
• how many neurons are active
• manipulations that change the activity of many
  neurons a little have a show bigger activation
  differences than manipulations that change the
  activation of a few neurons a lot
• attention
• ? activity
• learning
• ? activity
• fMRI may not
• match single neuron
• physiology results

Raichle Posner, Images of Mind cover image
Ideas from Scannell Young, 1999, Proc Biol Sci
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The Concise Summary
We sort of understand this (e.g., psychophysics,
neurophysiology)
We sort of understand this (MR Physics)
Were _at_ clueless here!
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Bottom Line

• Despite all the caveats, questions and concerns,
  BOLD imaging is well-correlated with results from
  other methods
• BOLD imaging can resolve activation at a fairly
  small scale (e.g., retinotopic mapping)
• PSPs and action potentials are correlated so
  either way, its getting at something meaningful
• even if BOLD activation doesnt correlate
  completely with electrophysiology, that doesnt
  mean its wrong
• may be picking up other processing info (e.g.,
  PSPs, synchrony)

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If time permits
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Positron Emission Tomography (PET)

• radioactive isotopes emit positrons
• positrons collide with electrons, emitting two
  photons (gamma rays) in opposite directions
• detectors surrounding brain register simultaneous
  photons and compute likely source

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PET

• Most cognitive studies are done with H215O
  labelled water via I.V. injection
• radioactive oxygen absorbed throughout body
• regions of brain with highest blood flow will
  have increased concentrations of radioactive
  oxygen
• resolution of several mm

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PET

• Compares regional cerebral blood flow (rCBF)
  between states
• A modern PET scanner integrates over 45-60 s
• Need to wait a number of half-lives before next
  injection

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PET vs. fMRI

• fMRI does not require exposure to radiation
• fMRI can be repeated
• fMRI has better spatial and temporal resolution
• requires less averaging
• can resolve brief single events
• MRI is becoming very common PET is specialized
• MRI can obtain anatomical and functional images
  within same session
• PET can resolve some areas of the brain better
• in PET, isotopes can tagged to many possible
  tracers (e.g., glucose or dopamine)
• PET can provide more direct measures about
  metabolic processes

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Spatial and Temporal Resolution
Gazzaniga, Ivry Mangun, Cognitive Neuroscience
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The Brain Before fMRI (1957)
Polyak, in Savoy, 2001, Acta Psychologica
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JODY THE FOLLOWING SLIDES ARE FROM THE OLD 4
DUMMMIES PAGE
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Section 2Basic fMRI Physics
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Other Resources
These slides were condensed from several
excellent online sources. I have tried to give
credit where appropriate. If you would like a
more thorough introductory review of MR physics,
I suggest the following
Robert Coxs slideshow, (f)MRI Physics with
Hardly Any Math, and his book chapters online.
http//afni.nimh.nih.gov/afni/edu/ See
Background Information on MRI section Mark
Cohens intro Basic MR Physics slides http//porkp
ie.loni.ucla.edu/BMD_HTML/SharedCode/MiscShared.ht
ml Douglas Nolls Primer on MRI and Functional
MRI http//www.bme.umich.edu/dnoll/primer2.pdf F
or a more advanced tutorial, see Joseph Hornaks
Web Tutorial, The Basics of MRI http//www.cis.rit
.edu/htbooks/mri/mri-main.htm
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Recipe for MRI

• 1) Put subject in big magnetic field (leave him
  there)
• 2) Transmit radio waves into subject about 3
  ms
• 3) Turn off radio wave transmitter
• 4) Receive radio waves re-transmitted by subject
• Manipulate re-transmission with magnetic fields
  during this readout interval 10-100 ms MRI
  is not a snapshot
• 5) Store measured radio wave data vs. time
• Now go back to 2) to get some more data
• 6) Process raw data to reconstruct images
• 7) Allow subject to leave scanner (this is
  optional)

Source Robert Coxs web slides
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History of NMR
NMR nuclear magnetic resonance Felix Block and
Edward Purcell 1946 atomic nuclei absorb and
re-emit radio frequency energy 1952 Nobel prize
in physics nuclear properties of nuclei of
atoms magnetic magnetic field required resonance
interaction between magnetic field and radio
frequency
Bloch
Purcell
NMR ? MRI Why the name change?
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History of fMRI
MRI -1971 MRI Tumor detection (Damadian) -1973
Lauterbur suggests NMR could be used to form
images -1977 clinical MRI scanner
patented -1977 Mansfield proposes echo-planar
imaging (EPI) to acquire images
faster fMRI -1990 Ogawa observes BOLD effect
with T2 blood vessels became more visible as
blood oxygen decreased -1991 Belliveau observes
first functional images using a contrast
agent -1992 Ogawa et al. and Kwong et al.
publish first functional images using BOLD signal
Ogawa
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Necessary Equipment
4T magnet
RF Coil
gradient coil (inside)
Magnet
Gradient Coil
RF Coil
Source Joe Gati, photos
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The Big Magnet
Very strong
Continuously on
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Magnet Safety
The whopping strength of the magnet makes safety
essential. Things fly Even big things!
Source www.howstuffworks.com
Source http//www.simplyphysics.com/ flying_objec
ts.html
Screen subjects carefully Make sure you and all
your students staff are aware of
hazzards Develop stratetgies for screening
yourself every time you enter the magnet
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Subject Safety

• Anyone going near the magnet subjects, staff
  and visitors must be thoroughly screened
• Subjects must have no metal in their bodies
• pacemaker
• aneurysm clips
• metal implants (e.g., cochlear implants)
• interuterine devices (IUDs)
• some dental work (fillings okay)
• Subjects must remove metal from their bodies
• jewellery, watch, piercings
• coins, etc.
• wallet
• any metal that may distort the field (e.g.,
  underwire bra)
• Subjects must be given ear plugs (acoustic noise
  can reach 120 dB)

This subject was wearing a hair band with a 2 mm
copper clamp. Left with hair band. Right
without. Source Jorge Jovicich
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Protons
Can measure nuclei with odd number of
neutrons 1H, 13C, 19F, 23Na, 31P 1H
(proton) abundant high concentration in human
body high sensitivity yields large signals
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Protons align with field
Outside magnetic field

• randomly oriented

Inside magnetic field

• spins tend to align parallel or anti-parallel to
  B0
• net magnetization (M) along B0
• spins precess with random phase
• no net magnetization in transverse plane
• only 0.0003 of protons/T align with field

M
longitudinal axis
Longitudinal magnetization
transverse plane
Source Mark Cohens web slides
M 0
Source Robert Coxs web slides
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Radio Frequency
Turn your dial to 4T fMRI -- Broadcasting at a
frequency of 170.3 MHz!
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Larmor Frequency
Larmor equation f ?B0 ? 42.58 MHz/T At
1.5T, f 63.76 MHz At 4T, f 170.3 MHz
170.3
Resonance Frequency for 1H
63.8
1.5
4.0
Field Strength (Tesla)
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RF Excitation

• Excite Radio Frequency (RF) field
• transmission coil apply magnetic field along B1
  (perpendicular to B0) for 3 ms
• oscillating field at Larmor frequency
• frequencies in range of radio transmissions
• B1 is small 1/10,000 T
• tips M to transverse plane spirals down
• analogies guitar string (Noll), swing (Cox)
• final angle between B0 and B1 is the flip angle

Transverse magnetization
Source Robert Coxs web slides
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Coxs Swing Analogy
Source Robert Coxs web slides
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Relaxation and Receiving

• Receive Radio Frequency Field
• receiving coil measure net magnetization (M)
• readout interval (10-100 ms)
• relaxation after RF field turned on and off,
  magnetization returns to normal
• longitudinal magnetization? ? T1 signal
  recovers
• transverse magnetization? ? T2 signal decays

Source Robert Coxs web slides
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T1 and TR

• T1 recovery of longitudinal (B0) magnetization
• used in anatomical images
• 500-1000 msec (longer with bigger B0)
• TR (repetition time) time to wait after
  excitation before sampling T1

Source Mark Cohens web slides
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Spatial CodingGradients

• How can we encode spatial position?
• Example axial slice

• Use other tricks to get other two dimensions
• left-right frequency encode
• top-bottom phase encode

Gradient switching thats what makes all the
beeping buzzing noises during imaging!
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Precession In and Out of Phase

• protons precess at slightly different
  frequencies because of
• (1) random fluctuations in the local field at the
  molecular level that affect both T2 and T2 (2)
  larger scale variations in the magnetic field
  (such as the presence of deoxyhemoglobin!) that
  affect T2 only.
• over time, the frequency differences lead to
  different phases between the molecules (think of
  a bunch of clocks running at different rates at
  first they are synchronized, but over time, they
  get more and more out of sync until they are
  random)
• as the protons get out of phase, the transverse
  magnetization decays
• this decay occurs at different rates in
  different tissues

Source Mark Cohens web slides
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T2 and TE
T2 decay of transverse magnetization TE (time
to echo) time to wait to measure T2 or T2
(after refocussing with spin echo or gradient
echo)
Source Mark Cohens web slides
59
Echos
pulse sequence series of excitations, gradient
triggers and readouts

• Echos refocussing of signal
• Spin echo
• use a 180 degree pulse to mirror image the
  spins in the transverse plane
• when fast regions get ahead in phase, make them
  go to the back and catch up
• measure T2
• ideally TE average T2
• Gradient echo
• flip the gradient from negative to positive
• make fast regions become slow and vice-versa
• measure T2
• ideally TE average T2

Gradient echo pulse sequence
t TE/2
A gradient reversal (shown) or 180 pulse (not
shown) at this point will lead to a recovery of
transverse magnetization
TE time to wait to measure refocussed spins
Source Mark Cohens web slides
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T1 vs. T2
Source Mark Cohens web slides
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K-Space
Source Travelers Guide to K-space (C.A.
Mistretta)
62
A Walk Through K-space
single shot
two shot

• K-space can be sampled in many shots
• (or even in a spiral)
• 2 shot or 4 shot
• less time between samples of slices
• allows temporal interpolation

Note The above is k-space, not slices
vs.
1st volume in 1 sec
63
T2

• T2 relaxation
• dephasing of transverse magnetization due to
  both
• - microscopic molecular
  interactions (T2)
• - spatial variations of the
  external main field ?B
• (tissue/air, tissue/bone
  interfaces)
• exponential decay (T2 ? 30 - 100 ms, shorter
  for higher Bo)

Mxy
Mo sin?
T2
T2
time
Source Jorge Jovicich
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Susceptibility
Adding a nonuniform object (like a person) to B0
will make the total magnetic field nonuniform
This is due to susceptibility generation of
extra magnetic fields in materials that are
immersed in an external field For large scale
(10 cm) inhomogeneities, scanner-supplied
nonuniform magnetic fields can be adjusted to
even out the ripples in B this is called
shimming

• Susceptibility Artifact
• -occurs near junctions between air and tissue
• sinuses, ear canals
• -spins become dephased so quickly (quick T2), no
  signal can be measured

sinuses
ear canals
Susceptibility variations can also be seen around
blood vessels where deoxyhemoglobin affects T2
in nearby tissue
Source Robert Coxs web slides
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Hemoglobin
Hemoglogin (Hgb) - four globin chains -
each globin chain contains a heme group - at
center of each heme group is an iron atom (Fe)
- each heme group can attach an oxygen atom
(O2) - oxy-Hgb (four O2) is diamagnetic ? no
?B effects - deoxy-Hgb is paramagnetic ? if
deoxy-Hgb ? ? local ?B ?
Source http//wsrv.clas.virginia.edu/rjh9u/hemog
lob.html, Jorge Jovicich
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BOLD signal
Blood Oxygen Level Dependent signal

• neural activity ? ? blood flow ? ? oxyhemoglobin
  ? ? T2 ? ? MR signal

Mxy Signal
Mo sin?
T2 task
T2 control
Stask
?S
Scontrol
time
TEoptimum
Source fMRIB Brief Introduction to fMRI
Source Jorge Jovicich
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BOLD signal
Source Doug Nolls primer
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First Functional Images
Source Kwong et al., 1992
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Hemodynamic Response Function
signal change (point baseline)/baseline usu
ally 0.5-3 initial dip -more focal and
potentially a better measure -somewhat elusive so
far, not everyone can find it
time to rise signal begins to rise soon after
stimulus begins time to peak signal peaks 4-6
sec after stimulus begins post stimulus
undershoot signal suppressed after stimulation
ends
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Review
Magnetic field
Tissue protons align with magnetic
field (equilibrium state)
RF pulses
Protons absorb RF energy (excited state)
Spatial encoding using magnetic field gradients
Relaxation processes
Relaxation processes
Protons emit RF energy (return to equilibrium
state)
NMR signal detection
Repeat
RAW DATA MATRIX
Fourier transform
IMAGE
Source Jorge Jovicich