fMRI: History and Physics

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fMRI History and Physics
Seong-Gi Kim, Radiology, Pitt
History of fMRI

• 1. Development of MRI
• Functional studies in animals
• Initial human functional studies
• 4. Key further developments

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Discovery of Magnetic Resonance Imaging2003
Nobel Prize "for their discoveries concerning
magnetic resonance imaging"
Paul Lauterbur, Nature, 1973
Sir Peter Mansfield development of fast
imaging technique
Imaging of water proton
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Conception of Blood Oxygenation Level Dependent
(BOLD) MRI Contrast by Seiji Ogawa at ATT Bell
Lab.
Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic
resonance imaging with contrast dependent on
blood oxygenation Proc Natl Acad Sci U S A.
1990 Dec87(24)9868-72. Ogawa S, Lee TM.
Magnetic resonance imaging of blood vessels at
high fields in vivo and in vitro measurements
and image simulation Magn Reson Med. 1990
Oct16(1)9-18. Ogawa S, Lee TM, Nayak AS, Glynn
P. Oxygenation-sensitive contrast in magnetic
resonance image of rodent brain at high magnetic
fields Magn Reson Med. 1990 Apr14(1)68-78.
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Blood Oxygenation Level-dependent Contrast
Ogawa et al. MRM, 1990
- Oxyhemoglobin is diamagnetic (like biological
tissue).
- Deoxyhemoglobin (dHb) is paramagnetic
increase transverse relaxation rate (R2) of
water protons induce susceptibility effect
around dHb
Breathing 100 O2
Breathing air
Mouse brain images at 360 MHz
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Dynamic BOLD MR Measurements in Cats
Turner R, Le Bihan D, Moonen CT, Despres D, Frank
J Echo-planar time course MRI of cat brain
oxygenation changes Magn Reson Med. 1991
Nov22(1)159-66 Abstract When deoxygenated,
blood behaves as an effective susceptibility
contrast agent. Changes in brain oxygenation can
be monitored using gradient-echo echo-planar
imaging. With this technique, difference images
also demonstrate that blood oxygenation is
increased during periods of recovery from
respiratory challenge.
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First Human fMRI Study
JW Belliveau, DN Kennedy Jr, RC McKinstry, BR
Buchbinder, RM Weisskoff, MS Cohen, JM Vevea, TJ
Brady, and BR Rosen, Functional mapping of the
human visual cortex by magnetic resonance
imaging, Science, Vol 254, Issue 5032, 716-719,
1991
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First Human BOLD fMRI Studies
Ogawa S, Tank DW, Menon R, Ellermann JM, Kim SG,
Merkle H, Ugurbil K. Intrinsic signal changes
accompanying sensory stimulation functional
brain mapping with magnetic resonance imaging,
Proc Natl Acad Sci U S A. 1992 Jul
189(13)5951-5.
Kwong KK, Belliveau JW, Chesler DA, Goldberg IE,
Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE,
Cohen MS, Turner R, et al. Dynamic magnetic
resonance imaging of human brain activity during
primary sensory stimulation, Proc Natl Acad Sci
U S A. 1992 Jun 1589(12)5675-9.
Bandettini PA, Wong EC, Hinks RS, Tikofsky RS,
Hyde JS, Time course EPI of human brain function
during task activation, Magn Reson Med. 1992
Jun25(2)390-7
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BOLD fMRI in Human Primary Visual Cortex
Functional Image (Visual Stimulation)
Anatomical Image
University of Minnesota, 4 Tesla Ogawa et al.
Proc Natl Acad Sci USA, 1992
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Application to brain research ---
December 1992
January 1993
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Further fMRI Technical Advances Cerebral Blood
Flow
Edelman RR, Siewert B, Darby DG, Thangaraj V,
Nobre AC, Mesulam MM, Warach S. Qualitative
mapping of cerebral blood flow and functional
localization with echo-planar MR imaging and
signal targeting with alternating radio
frequency, Radiology. 1994 Aug192(2)513-20
Kim SG, Quantification of relative cerebral
blood flow change by flow-sensitive alternating
inversion recovery (FAIR) technique application
to functional mapping, Magn Reson Med. 1995
Sep34(3)293-301
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fMRI Technical Advances Oxygen Consumption
Kim Ugurbil, Comparison of Blood Oxygenation
and Cerebral Blood Flow Effects in fMRI
Estimation of Relative Oxygen Consumption Change,
Magn. Reson. Med., 38 59-65, 1997
Davis et al. Calibrated functional MRI mapping
the dynamics of oxidative metabolism. Proc Natl
Acad Sci USA 95 1834-1839, 1998

• Kim et al., Determination of Relative CMRO2 from
  CBF and BOLD changes Significant oxygen
  consumption rate during visual stimulation,
  Magn. Reson. Med., 41 1152-1161, 1999
• Hoge et al., Linear coupling between cerebral
  blood flow and oxygen consumption in activated
  human cortex, Proc Natl Acad Sci U S A. 96
  9403-8, 1998

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hypercapnia
Visual stimulation
30 - 80
0.5 - 2
30 - 80
Subject 1
CBF
BOLD
CMRO2
Subject 2
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fMRI History and Physics
Biophysics of fMRI
Basics of MRI Property of Hemoglobin Signal
Source of BOLD fMRI
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MRI Basics
electrons
nucleus (protons nucleons)
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MRI Basics
(without external magnetic field)
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MRI Basics
RF pulse
?0 ??B0
For proton,
frequency (MHz) 42.58?B0 (T)
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MRI Basics
RF pulse
?0 ??B0
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Bo
M
time
FREQUENCY (w gBo ) PHASE
AMPLITUDE SIGNAL DECAY RATE
(Characterized with time constant T2)
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SIGNAL DECAY IS DOMINATED BY Irreversible
processes (T2) Dephasing due to different
frequency of precession in the presence
of magnetic field inhomogeneities
(reversible) (T2).
1/T2 is the time constant that Characterizes
decay due to both processes.
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RF Pulse
(Signal Excitation)
Echo Time (TE)
IMAGE ACQUISITION
time
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MRI Signal function of spin
density, relaxation parameters (T1, T2, T2)
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BOLD (BLOOD OXYGEN DEPENDENT CONTRAST) CONTRAST
Seiji Ogawa, ATT Bell Lab, 1990
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Properties of Red Blood Cells Hemoglobin (Hb)
Red blood cells (erythrocytes) contain
hemoglobin which is bright red in color. Make up
40 of blood volume
Flattened disk, 6 µm wide 1-2 µm thick
Each Hb carries 4 O2
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Hemoglobin Oxygen Dissociation Curve
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Magnetic property of Oxyhemoglobin vs.
Deoxyhemoglobin
Pauling Coryell, PNAS, 1936
- Oxyhemoglobin is diamagnetic (like biological
tissue).
Magnetic field
- Deoxyhemoglobin (dHb) is paramagnetic induce
susceptibility effect around dHb
q
vessel
f
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Vascular Structure
Capillaries
Arteries
Veins
Blood oxygenation level
1.0
0.6
Distance
(Fox et al., Science 1988)
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Compartmentalization of Water
Intravascular water moves freely Slow exchange
of IV and EV water Intact BBB ? tight junctions
between endothelial cells impede the diffusion
of water. (In 50 ms, less than 5 of the
capillary water diffuses into the
EVS.) Extravascular water moves freely
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Intravascular Effect -gt T2 Change
Reb Blood Cell
water
Water appears to move freely across the RBC
membrane (residence time in RBC 5 ms).
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Susceptibility effect in Extravascular Pool
?Bout
1 of max at r 10 a.
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Susceptibility effect in Extravascular Pool
?Bout
MRI signal at echo time (TE) a summation of all
water proton signal within a voxel. Each proton
signal decays by T2 and dephases by local
susceptibility effect (i.e., Phase shift)
S(TE) ? S.exp(-TE/T2).e(-i?TE) ?
S.exp(-TE/T2)
1 of max at r 10 a.
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EXTRA-VASCULAR BOLD Dependence on Vessel Size

• LARGE blood vessels (veins, venules)
• R2 ( 1/T2) ? BO(1 - Y)CBVlv
• SMALL blood vessels (capillaries, post capillary
  venules)
• R2 ? BO(1 - Y)2 CBVsv

Large venous vessel volume
Venous oxygenation level
Small venous vessel volume
Ogawa et al.,1993
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How do you determine an echo time for fMRI?
?S Soexp(-TE/T2st) - exp(-TE/T2cont)
Soexp(-TE/T2cont)exp(-TE ?R2 1) -
Soexp(-TE/T2cont)(TE ?R2) - Scont(TE
?R2)
TE T2 of tissue for Gradient-echo BOLD fMRI
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Neural activity-induced T2 change
TE T2 of tissue absolute signal change (?S)
TE x ?(1/T2) x exp(-TE/T2)
Signal decay term
?S
TE
T2 is dependent on magnetic field and brain
regions subcortical regions with iron deposition
temporal or frontal regions with large
susceptibility effects from sinus -gt shorter
T2 gt shorter TE for optimal signal change
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Gradient-echo BOLD maps at 4.7T
1 mm
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Pulse Sequence vs. Susceptibility Effect
Conventional Gradient Echo
STATIC and DYNAMIC Averaging are both detected
(T2)
ACQUIRE DATA
Spin Echo
DYNAMIC Averaging is detected (T2)
ACQUIRE DATA
180 Pulse
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Capillary tube (1.4 mm o.d., 1.0 mm i.d.) filled
with blood in a saline bath.
GE
SE
oHb
B0
dHb
B0
dHb
Ogawa et al., MRM, 1990
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Extravascular and Intravascular BOLD Signal
Contributions
GE SE
Large vessels Small vessels
X X X X
X X X
EV
Large Small
IV
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Signal Profiles across the Cortex
Zhao et al, MRM, 2005.
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Conclusion BOLD Signals
The BOLD signal is dependent on Bo, TE, pulse
sequence (GE vs SE) vessel size, orientation,
and density venous oxygenation and volume changes
-gt Quantification of fMRI responses as a
meaningful physiological parameter is
difficult -gt Difficulty to compare across
subjects, especially with abnormal vascular
conditions