Transcript An Introduction to Functional MRI Duke-UNC Brain Imaging and Analysis Center FMRI Graduate Course Dr.

An Introduction to
Functional MRI
Duke-UNC Brain Imaging and Analysis Center
FMRI Graduate Course
Dr. Scott Huettel
Summary of the Course
• Combines lectures and laboratory sessions
– Laboratories will illustrate concepts from lectures
• Grading basis
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Participation in course sessions (attendance, discussion)
Completion of laboratory exercises
Self-assessment questions (for students)
Possibly one take-home test (mid-term)
Practicum research project at end of semester
• Course web page (www.biac.duke.edu\education)
• Readings
– Functional Magnetic Resonance Imaging (Huettel, Song, McCarthy)
– Original papers, posted to web site
– Supplementary readings are provided in textbook chapters
Logistics Issues
• BIAC log-ins required for laboratory
– Not “Duke NetID”
– Will give access to Class.01 Directory
– Even if you already have a login, you will still need
access to Class.01
• Readings available via website and downloads
– PDFs of original papers in Class.01\Students\Readings
• Lecture PowerPoint files will be posted on website
after each session
Who are we?
• Brain Imaging and Analysis Center
– Independent center within DUMC with Duke and UNC-CH faculty
– Two research-dedicated MRI scanners (3T and 4T)
• Collaborative Mission:
– To support the development of neuroimaging at our institutions.
• Research Mission:
– To advance the understanding of brain structure and function through
application of neuroimaging.
• Course Faculty
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Scott Huettel (Course Director)
Jim Voyvodic
Allen Song
Gregory McCarthy
Kevin Pelphrey
Outline for Today
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What is fMRI?
History
Key concepts
Parts of a MR scanner
MR safety
• Laboratory: Scanner Visit (Dr. Jim Voyvodic)
– Scanner hardware
– Stimulus presentation and recording hardware
– Demonstration of real-time fMRI
What is fMRI?
Functional Magnetic Resonance Imaging
• Uses a standard MRI scanner to acquire images of
functionally meaningful brain activity
• Typically measures changes in blood oxygenation
• Non-invasive, no ionizing radiation
• Good combination of spatial / temporal resolution
– Voxel sizes ~4mm
– Time of Repetition (TR) ~1s
Successes of Functional Imaging
Cheng, Waggoner, & Tanaka (2001) Neuron
King-Casas et al. (2005) Science
Why Image Brain Function?
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Understanding Cognition
Improving Clinical procedures
Studying Brain Development
Investigating Brain Physiology
Mapping Cognition to the Brain
• Brain imaging improves models for cognitive
processes
– Activation-based dissociations
• Brain imaging guides understanding of the relative
timing/structure of cognitive processes
• Brain imaging facilitates integration of
information from other techniques
– Lesion studies, animal work, brain disorders
Clinical Uses of FMRI
• Brain Tumors
– Direct: Mapping of functional properties of adjacent tissue
– Indirect: Understanding of likely consequences of a treatment
Image provided by Dr. James Voyvodic (Duke BIAC)
Clinical Uses of FMRI
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Brain Tumors
Drug Abuse/Addiction
Drug Studies
Neuropsychological disorders
Development
• Aging
– Which brain changes are associated with normal aging?
– Which changes are pathological?
• Childhood
– How does the human brain develop from birth to
maturity?
– Could we improve educational or health policies
through a better understanding of the brain?
• Longitudinal Studies
History of fMRI
Timeline of MR Imaging
1924 - Pauli suggests
that nuclear particles
may have angular
momentum (spin).
1972 – Damadian
patents idea for large
NMR scanner to
detect malignant
tissue.
1937 – Rabi measures
magnetic moment of
nucleus. Coins
“magnetic resonance”.
1944 – Rabi wins
Nobel prize in
Physics.
1952 – Purcell and
Bloch share Nobel
prize in Physics.
1920
1930
1940
1950
1946 – Purcell shows
that matter absorbs
energy at a resonant
frequency.
1946 – Bloch demonstrates
that nuclear precession can be
measured in detector coils.
1960
1959 – Singer
measures blood flow
using NMR (in
mice).
1985 – Insurance
reimbursements for
MRI exams begin.
1973 – Lauterbur
publishes method for
generating images
using NMR gradients.
MRI scanners
become clinically
prevalent.
NMR becomes MRI
1970
1980
1973 – Mansfield
independently
publishes gradient
approach to MR.
1975 – Ernst
develops 2D-Fourier
transform for MR.
1990
2000
1990 – Ogawa and
colleagues create
functional images
using endogenous,
blood-oxygenation
contrast.
Rabi and the Measurement of the
Nuclear Magnetic Moment (1937)
Discovery of Nuclear Magnetic
Resonance Absorption (1946)
• Bloch and Purcell independently
discovered how to measure nuclear
moment of bulk matter (1946)
• They showed that energy applied
at a resonant frequency was
absorbed by matter, and the reemission could be measured in
detector coils
Felix Bloch
• They shared the 1952 Nobel Prize
in Physics
Edward Purcell
Timeline of MR Imaging
1924 - Pauli suggests
that nuclear particles
may have angular
momentum (spin).
1972 – Damadian
patents idea for large
NMR scanner to
detect malignant
tissue.
1937 – Rabi measures
magnetic moment of
nucleus. Coins
“magnetic resonance”.
1944 – Rabi wins
Nobel prize in
Physics.
1952 – Purcell and
Bloch share Nobel
prize in Physics.
1920
1930
1940
1950
1946 – Purcell shows
that matter absorbs
energy at a resonant
frequency.
1946 – Bloch demonstrates
that nuclear precession can be
measured in detector coils.
1960
1959 – Singer
measures blood flow
using NMR (in
mice).
1985 – Insurance
reimbursements for
MRI exams begin.
1973 – Lauterbur
publishes method for
generating images
using NMR gradients.
MRI scanners
become clinically
prevalent.
NMR becomes MRI
1970
1980
1973 – Mansfield
independently
publishes gradient
approach to MR.
1975 – Ernst
develops 2D-Fourier
transform for MR.
1990
2000
1990 – Ogawa and
colleagues create
functional images
using endogenous,
blood-oxygenation
contrast.
Early Uses of NMR
• Most early NMR was used for chemical analysis
– No medical applications
• 1971 – Damadian publishes and patents idea for using
NMR to distinguish healthy and malignant tissues
– “Tumor detection by nuclear magnetic resonance”, Science
– Proposes using differences in relaxation times
– No image formation method proposed
• 1973 – Lauterbur describes projection method for creating
NMR images
– Mansfield (1973) independently describes similar approach
The First ZMR NMR Image
Lauterbur, P.C. (1973). Image formation by induced local interaction: Examples employing
nuclear magnetic resonance. Nature, 242, 190-191.
Early Human MR
Images (Damadian)
Mink5 Image – Damadian (1977)
Digression: 2003 Nobel Controversy
Paul Lauterbur
Peter Mansfield
Raymond Damadian
New York Times
9, 2003
October
Nobel Press Release
October 6, 2003
Summary
Imaging of human internal organs with exact and non-invasive methods is very important for
medical diagnosis, treatment and follow-up. This year's Nobel Laureates in Physiology or Medicine
have made seminal discoveries concerning the use of magnetic resonance to visualize different
structures. These discoveries have led to the development of modern magnetic resonance imaging,
MRI, which represents a breakthrough in medical diagnostics and research. …
…
This year's Nobel Laureates in Physiology or Medicine are awarded for crucial achievements in the development
of applications of medical importance. In the beginning of the 1970s, they made seminal discoveries concerning
the development of the technique to visualize different structures. These findings provided the basis for the
development of magnetic resonance into a useful imaging method.
Paul Lauterbur discovered that introduction of gradients in the magnetic field made it possible to create twodimensional images of structures that could not be visualized by other techniques. In 1973, he described how
addition of gradient magnets to the main magnet made it possible to visualize a cross section of tubes with
ordinary water surrounded by heavy water. No other imaging method can differentiate between ordinary and
heavy water.
Peter Mansfield utilized gradients in the magnetic field in order to more precisely show differences in the
resonance. He showed how the detected signals rapidly and effectively could be analysed and transformed to an
image. This was an essential step in order to obtain a practical method. Mansfield also showed how extremely
rapid imaging could be achieved by very fast gradient variations (so called echo-planar scanning). This
technique became useful in clinical practice a decade later.
Timeline of MR Imaging
1924 - Pauli suggests
that nuclear particles
may have angular
momentum (spin).
1972 – Damadian
patents idea for large
NMR scanner to
detect malignant
tissue.
1937 – Rabi measures
magnetic moment of
nucleus. Coins
“magnetic resonance”.
1944 – Rabi wins
Nobel prize in
Physics.
1952 – Purcell and
Bloch share Nobel
prize in Physics.
1920
1930
1940
1950
1946 – Purcell shows
that matter absorbs
energy at a resonant
frequency.
1946 – Bloch demonstrates
that nuclear precession can be
measured in detector coils.
1960
1959 – Singer
measures blood flow
using NMR (in
mice).
1985 – Insurance
reimbursements for
MRI exams begin.
1973 – Lauterbur
publishes method for
generating images
using NMR gradients.
MRI scanners
become clinically
prevalent.
NMR becomes MRI
1970
1980
1973 – Mansfield
independently
publishes gradient
approach to MR.
1975 – Ernst
develops 2D-Fourier
transform for MR.
1990
2000
1990 – Ogawa and
colleagues create
functional images
using endogenous,
blood-oxygenation
contrast.
Physiology (BOLD Contrast)
Blood-OxygenationLevel Dependent
contrast
Using MRI to Study Brain Function
Visual Cortex: Kwong, et al., 1992
Somatosensory Cortex: Hammeke, et al., 1994
Growth in fMRI : Published Studies
1990
1991
1992
1993
1994
1995
Medline search on “functional magnetic resonance”,
“functional MRI”, and “fMRI”.
1996
Year 2004 = ~1500
1997
1998
1999
2000
2001
2002
2003
…
2004
0
200
400
600
800
1000
1200
1400
Key Concepts
Key Concepts
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Contrast
Spatial Resolution
Temporal Resolution
Functional Resolution
Contrast
Contrast: Anatomical
Contrast:
1) The intensity difference between quantities being measured by an
imaging system.
2) The quantity being measured.
Contrast-to-noise: The magnitude of the intensity difference between quantities
divided by the variability in their measurements.
Contrast: Functional
Contrast-to-noise is critical for fMRI: How effectively can we decide whether a
given brain region has property X or property Y?
Spatial Resolution: Voxels
Voxel: A small rectangular prism that is the basic sampling unit of fMRI.
Typical anatomical voxel: (1.5mm)3. Typical functional voxel: (4mm)3.
Spatial Resolution: Examples
~8mm2
~4mm2
~1.5mm2
~2mm2
~1mm2
Temporal Resolution
• Importance depends upon research question
– Type I: Detection
• Temporal resolution is only indirectly important if your study
investigates whether or not a given brain region is active.
– Type II: Estimation
• Temporal resolution is extremely important when attempting to
understand the properties of an active region.
• Determining factors
– Sampling rate, usually repetition time (TR)
– Dependent variable, usually BOLD response
• BOLD response is sluggish, taking 2-3 seconds to rise above
baseline and 4-6 seconds to peak
– Experimental design
Functional Resolution
The ability of a measurement technique to identify
the relation between underlying neuronal activity
and a cognitive or behavioral phenomenon.
Functional resolution is limited both by the intrinsic
properties of our brain measure and by our ability
to manipulate the experimental design to allow
variation in the phenomenon of interest.
MRI Scanners
Main Components of a Scanner
• Static Magnetic Field Coils
• Gradient Magnetic Field Coils
• Radiofrequency Coil
• Shimming Coils
• Data transfer and storage computers
• Physiological monitoring, stimulus display, and
behavioral recording hardware
Static and Gradient Magnetic Fields
Static and Gradient Magnetic Fields
Surface Coil
Volume Coil
Shimming Coils
• Used to compensate for magnetic field inhomogeneities
– May be first order (X or Y) or of higher orders (X3)
– May be along single gradient or multiple gradients (XY)
• Types of shim systems on BIAC scanners
– Passive: Large number of metal rods w/ adjustable weights
• Adjusted infrequently (i.e., after ramping up)
– Superconducting: Coils surrounded by cryogens
• Expensive, adjusted infrequently
– Resistive: Coils at room-temperature
• Cheaper, adjusted for each subject
Pulse Sequences
T1
T2
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Recipes for controlling scanner hardware
Allow MR to be extremely flexible
MRI Safety
Issue: The appropriate risk level for a research participant is
much lower than for a clinical patient, because the latter
receives benefit from the MR examination.
Hospital Nightmare
Boy, 6, Killed in Freak MRI Accident
July 31, 2001 — A 6-year-old boy died after
undergoing an MRI exam at a New Yorkarea hospital when the machine's powerful
magnetic field jerked a metal oxygen tank
across the room, crushing the child's
head. …
ABCNews.com
MR Incidents
• Pacemaker malfunctions leading to death
– At least 5 as of 1998 (Schenck, JMRI, 2001)
– E.g., in 2001 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)
Issues in MR Safety
• Known acute risks
– Projectiles, rapid field changes, RF heating,
claustrophobia, acoustic noise, etc.
• Potential risks
– Current induction in tissue at high fields
– Changes in the developing brain
• Epidemiological studies of chronic risks
– Extended exposure to magnetic fields
• Difficulty in assessing subjective experience
– In one study, 45% of subjects exposed to a 4T scanner
reported unusual sensations (Erhard et al., 1995)
Possible Effects of Magnetic Fields
• Physiological
– Red blood cells (especially sickled) may alter shape in a
magnetic field
– Some photoreceptors may align with the field.
• Sensory (generally reported in high-field)
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Nausea
Vertigo
Metallic taste
Magnetophosphenes
Risks of MRI
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Projectile Effects: External
Projectile Effects: Internal
Radiofrequency Energy
Gradient field changes
Claustrophobia
Acoustic Noise
Quenching
Projectile Effects: External
Chaljub (2001)
Schenck (1996)
“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
Chaljub (2001)
Radiofrequency Energy
• Tissue Heating
– Specific Absorption Rate (SAR; W/kg)
• Pulse sequences are limited to cause less than a one-degree rise in
core body temperature
• Scanners can be operated at up to 4 W/kg (with large safety margin)
for normal subjects, 1.5 W/kg for compromised patients (infants,
fetuses, cardiac)
– Weight of subject critical for SAR calculations
• Burns
– Looped wires can act as RF antennas and focus energy in a small
area
• Most common problem: ECG leads
• Necklaces, earrings, piercings, pulse oximeters, any other cabling
Projectile/Torsion Effects: Internal
• Motion of implanted medical devices
– Clips, shunts, valves, etc.
• Motion or rotation of debris, shrapnel, filings
– Primary risk: Metal fragments in eyes
• Swelling/irritation of skin due to motion of iron
oxides in tattoo and makeup pigments
Acoustic Noise
• Potential problem with all scans
– Short-term and long-term effects
• Sound level of BIAC scanners
– 1.5T: 93-98 dB (EPI)
– 4.0T: 94-98 dB (EPI)
• OSHA maximum exposure guidelines
– 2-4 hours per day at BIAC levels
• Earplugs reduce these values by 14-29 dB.
Gradient Field Changes (dB/dt)
• Peripheral nerve stimulation
– May range from distracting to painful
– Risk greatly increased by conductive loops
• Arms clasped
• Legs crossed
• Theoretical risk of cardiac stimulation
– No evidence for effects at gradient strengths
used in MRI
Claustrophobia
• Most common subject problem
– About 10% of patients
– About 1-2% of BIAC subjects
• Ameliorated with comfort measures
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Talking with subject
Air flow through scanner
Panic button
Slow entry into scanner
Quenching
• Definition: Rapid decrease in magnetic field strength due to
loss of superconductivity
– Only initiated voluntarily due to danger to participant’s life or health
• Effects
– Magnets heat up with loss of current
– Cryogenic fluids (Helium) boil off and fill the scanner room
• Displaces breathable air from room
• Cooling of room, condensation reduces visibility
– Physical damage to the scanner may occur
– Safety personnel must be cognizant of room conditions
Scanner Tour
• Dr. Jim Voyvodic will demonstrate real-time fMRI
– We will see the 3T BIAC scanner in action
– Go through the mock scanner
• Generally low field
– Anyone with pacemaker, other implanted metal (shunts,
clips, etc.) should tell instructor
– Fillings, piercings fine (for console room)
• Auditors remain in room for brief discussion