introduction to functional mri jody culham brain and mind institute department of psychology...
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Introduction to Functional MRI
Jody CulhamBrain and Mind Institute
Department of PsychologyUniversity of Western Ontario
http://www.fmri4newbies.com/
MAIN SOURCES:
FMRI Graduate Course (NBIO 381, PSY 362)Dr. Scott HuettelDuke-UNC Brain Imaging & Analysis Center (BIAC)
http://www.biac.duke.edu/education/courses/
Karla L. MillerFMRIB CentreOxford University
http://www.fmrib.ox.ac.uk/~karla/
E = mc2
???
The First “Brain Imaging Experiment”
“[In Mosso’s experiments] the subject to be observed lay on a delicately balanced table which could tip downward either at the head or at the foot if the weight of either end were increased. The moment emotional or intellectual activity began in the subject, down went the balance at the head-end, in consequence of the redistribution of blood in his system.”
-- William James, Principles of Psychology (1890)
Angelo MossoItalian physiologist
(1846-1910)
… and probably the cheapest one too!
FMRI – Week 1 – IntroductionScott Huettel, Duke University
Timeline of MR Imaging
1920 1930 1940 1950 1960 1970 1980 1990 2000
1924 - Pauli suggests that nuclear particles may have angular momentum (spin).
1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”.
1944 – Rabi wins Nobel prize in Physics.
1946 – Purcell shows that matter absorbs energy at a resonant frequency.
1946 – Bloch demonstrates that nuclear precession can be measured in detector coils.
1952 – Purcell and Bloch share Nobel prize in Physics.
1972 – Damadian patents idea for large NMR scanner to detect malignant tissue.
1959 – Singer measures blood flow using NMR (in mice).
1973 – Lauterbur publishes method for generating images using NMR gradients.
1973 – Mansfield independently publishes gradient approach to MR.
1975 – Ernst develops 2D-Fourier transform for MR.
NMR becomes MRI
MRI scanners become clinically prevalent.
1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast.
1985 – Insurance reimbursements for MRI exams begin.
M R
FMRI – Week 1 – Introduction Scott Huettel, Duke University
Timeline of MR Imaging
1920 1930 1940 1950 1960 1970 1980 1990 2000
1924 - Pauli suggests that nuclear particles may have angular momentum (spin).
1937 – Rabi measures magnetic moment of nucleus. Coins “magnetic resonance”.
1944 – Rabi wins Nobel prize in Physics.
1946 – Purcell shows that matter absorbs energy at a resonant frequency.
1946 – Bloch demonstrates that nuclear precession can be measured in detector coils.
1952 – Purcell and Bloch share Nobel prize in Physics.
1972 – Damadian patents idea for large NMR scanner to detect malignant tissue.
1959 – Singer measures blood flow using NMR (in mice).
1973 – Lauterbur publishes method for generating images using NMR gradients.
1973 – Mansfield independently publishes gradient approach to MR.
1975 – Ernst develops 2D-Fourier transform for MR.
NMR becomes MRI
MRI scanners become clinically prevalent.
1990 – Ogawa and colleagues create functional images using endogenous, blood-oxygenation contrast.
1985 – Insurance reimbursements for MRI exams begin.
M R I f
The Rise of fMRI…
Friston, 2010,Science
Schleim & Roiser, 2009, Front. Hum. Neurosci.
… and the Decline of PET
FMRI – Week 1 – Introduction Scott Huettel, Duke University
Spatial vs. Temporal Resolution of Selected Brain Imaging Methods
The Brain Before fMRI (1957)
Polyak, in Savoy, 2001, Acta Psychologica fMRI for Dummies
moving bodiessocial cognition
faces objectsstatic bodies
grasping
motion perception
motion near head
orientation selectivitymemory
scenes
motorcontrol
reaching and pointing
touch
retinotopic visual maps eyemovements
executive control
The Brain After fMRI (Incomplete)
Magnetic Resonance ImagingScanner
fMRI Setup
[Source: Mouser.com]
K-Space
Source: Traveler’s Guide to K-space (C.A. Mistretta)
K-Space
• Data gathered in k-space (Fourier domain of image)• Image is Fourier transform of acquired data• How k-space is sampled has implications for image
k-space image space
Fouriertransform
ky
kx
ky
kx
Reduces TE (sacrifices some functional contrast)
Must acquire slightly more than half (Hermetian symmetry is approximate)
Slight blurring added to image
Partial k-space EPI
EPI acquires one imageper TR
Due to symmetry, canactually collect less thanfull k-space
Spiral FMRI
• Currently, only serious alternative to EPI
• Short apparent TE (center of k-space acquired early)
• Fast and efficient use of gradient hardware
• Different artifacts than EPI (not necessarily better)
• Coil sensitivity encodes spatial information
• Can “leave out” large parts of k-space– Theory: For n coils, only need 1/n of k-space– Practice: Need at least ~1/3 of k-space– In general, incurs loss of SNR
• More coverage, higher resolution, faster imaging, etc.
Parallel imaging (SENSE, SMASH, etc.)
Single coil 8-channel array
Surface coils
FMRI – Week 1 – IntroductionScott Huettel, Duke University
MR Safety• Pacemaker malfunctions leading to death
– At least 5 as of 1998 (Schenck, JMRI, 2001)– E.g., in 2000 an elderly man died in Australia after being twice asked if he
had a pacemaker
• Blinding due to movements of metal in the eye– At least two incidents (1985, 1990)
• Dislodgment of aneurysm clip (1992)
• Projectile injuries (most common incident type)– Injuries (e.g., cranial fractures) from oxygen canister (1991, 2001)– Scissors hit patient in head, causing wounds (1993)
• Gun pulled out of policeman’s hand, hitting wall and firing– Rochester, NY (2000)
MRI fMRI
series of 3D volumes (i.e., 4D data)(e.g., every 2 sec for 5 mins)
high spatial
resolution(1 mm)
low spatial resolution(~3-5 mm)
…
MRI vs. fMRI
one 3D volume(collected over several minutes)
PET and fMRI Activation
Source: Posner & Raichle, Images of Mind
fMRI Experiment Stages: Prep
1) Prepare subject• Consent form• Safety screening• Instructions and practice trials if appropriate
2) Shimming • putting body in magnetic field makes it non-uniform• adjust 3 orthogonal weak magnets to make magnetic field as homogenous as
possible
3) SagittalsTake images along the midline to use to plan slices
[Source: Wikipedia]
fMRI Experiment Stages: Anatomicals4) Take anatomical (T1) images
• high-resolution images (e.g., 0.75 x 0.75 x 3.0 mm)• 3D data: 3 spatial dimensions, sampled at one point in time• 64 anatomical slices takes ~4 minutes
64 axial slices (3 mm)
Slice Thicknesse.g., 6 mm
Gap, here 0 mm
Number of Slicese.g., 10
Slice prescription (on SAG slice)IN-PLANE SLICE
Field of View (FOV)e.g., 19.2 cm
VOXEL(Volumetric Pixel)
3 mm
3 mm6 mm
Slice Terminology
Matrix Sizee.g., 64 x 64
In-plane resolutione.g., 192 mm / 64
= 3 mm
fMRI Experiment Stages: Functionals5) Take functional (T2*) images
• images are indirectly related to neural activity• usually low resolution images (e.g. here 3 x 3 x 6 mm)• all slices at one time = a volume (sometimes also called an image)• sample many volumes (time points) (e.g., 1 volume every 2 seconds for 136
volumes = 272 sec = 4:32)• 4D data: 3 spatial, 1 temporal
…
fMRI Simplified
Time
Condition 1
Condition 2
~2s
...
~ 5 min
Region of interest (ROI)
Time
fMRISignal
Intensity
ROI Time Course
Condition
Ignoring: HRF, subject motion, multiple comparisons
BOLD Time CourseBlood Oxygenation Level-Dependent Signal
Positive BOLD response
InitialDip
OvershootPost-stimulusUndershoot
0
1
2
3
BO
LD R
espo
nse
(% s
igna
l cha
nge)
Time
Stimulus
The metabolic signal we track is actually time-lagged from neural activity…
“HRF”(Hemodynamic response function)
The Canonical FMRI Experiment
• Subject is given sensory stimulation or task, interleaved with control or rest condition
• Acquire timeseries of BOLD-sensitive images during stimulation
• Analyse image timeseries to determine where signal changed in response to stimulation
PredictedBOLD signal
time
Stimuluspattern
on
off
on
off
on
off
on
offoff
BOLD/Signal Time Courses
TIME
MR
SIG
NA
L(A
RB
ITR
AR
Y U
NIT
S)
BOLD signal has arbitrary units:
varies from coil to coil, voxel to voxel, day to day, subject to subject
Predicted HRF
Observed signal
BOLD/Signal Time Courses
TIME
MR
SIG
NA
L(%
Cha
nge)
Observed signal
Predicted HRF
Signal usually converted into units of % change:
Typically on the order of ½ - 4 %.
Final Statistics
• For convenience/summarization, time course at each voxel can be converted to a scalar measure
• Most common: parametric test of significance (e.g., t-test)
• “statistical parametric map”: voxel-wise parametric test results
Stats on Anatomical
2D 3D
Multiple Comparisons Problem
• Voxel-level statistics assume independence of all voxels (not true)
• Also, by virtue of the number of tests involved, conventional p-values are far too loose– p < 0.05 implies 5% chance of a false positive– Acceptable for one test, but with 100,000 tests (~ ½
brain size) that would be 5,000 false positives!…
• Many options: Bonferroni (conservative), familywise error rate (FWE), false discovery rate (FDR), cluster level significance, and others
Limitations of Neuroimaging
• Physical Limitations– spatial limitations (~1 mm)– temporal limitations (~50 ms to several seconds)
• Physiological Limitations– noise
• head motion• artifacts (respiration, cardiac pulse)
– localization of BOLD response• vasculature
• Current Conceptual Limitations– how can we analyze highly complex data sets?
• brain networks
– how are neural changes manifested in fMRI activation?
Limitations of Neuroimaging
Logothetis, 2008, Nature
Canonical cerebral microcircuit(excitatory in red, inhibitory in black)
BOLD signal mayIncrease or decrease,and this doesn’tnecessarily tell whatthe “neural input”or “neural output”was.
More complicated than just “taskrelated neuronsfiring”
BOLD Signal Dropout
BOLDNon-BOLD
Dephasing near air-tissue boundaries (e.g., sinuses)
BOLD contrast (using long TE) coupled to signal loss (“black holes”)
Additional Topics
• Practical steps for image analysis (next)• Biological sources of the BOLD signal• Physics and underpinnings of MR signal• Computational background on image processing steps• Experimental design
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