CMRR presentation

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fMRI Interpretation, Limits and Potential
Pitfalls
Seong-Gi Kim
Spatial Resolution Temporal Resolution Examples
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Oxy vs. Deoxy Hemoglobin
Deoxyhemoglobin
Oxyhemoglobin
PARAMAGNETIC
DIAMAGNETIC (Similar toTissue)
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Vessel vs. Voxel Size
3 x 3 x 3 mm many vessels, but relatively
uniform vessel distribution (3-5)
Torre et al.
430 µm
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Spatial Specificity of BOLD Signal to Neural
Activity Site

• Venous Vascular Structures

Pial Venous Vessels 130 380 ?m
diameter Intracortical Veins 80 120 ?m
average diameter 1 2 mm apart
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Parenchymal Microvessel (lt50 ?m diameter)
Region Blood volume Hct Occipital
cortex 1 33 Corpus callosum 0.4 32 Cer
ebellar nuclei 1.3 34 Systematic
blood 40-45
Rat Fenstermacher et al.
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Distance between Intracortical Veins
artery
vein
Pia
GM
WM
Distance between emerging venous veins 0.75 - 4
mm
Duvernoy et al. Brain Research Bulletin, 1981
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Cortical Depth-Dependent High resolution fMRI at
9.4T
(156x 156 µm2 in-resolution, 4-shot EPI, 9.4T)
visual cortex
Coronal
BOLD
T2-weighted, TE20 ms
Zhao et al.
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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
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Conventional Gradient-echo and Spin-echo BOLD
Signal
CBV 2 ?? 0.1 ppm
Boxerman et al., MRM, 1995
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Comparison between GE and SE BOLD fMRI at 9.4T
Spin-Echo
Gradient-Echo
Cat 1
Cat 2
Zhao et al.
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Signal Profiles across the Cortex
Zhao et al.
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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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BOLD Signals
Dependent on Bo, TE, pulse sequence (GE vs
SE) Dependent on vessel size, orientation, and
density Dependent on hematocrit level Dependent
on oxygenation level
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Blood-pool Contrast Agent

• - Blood pool contrast agents iron oxides (MION)
  
• (typical 10 mg Fe/kg body)
• Reduce signals at large vessel areas.

i.v. injection of long half-life contrast agents
Rosen et al., 1991 Mandeville et al., 1998
Kennan et al., 1998
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fMRI with exogenous contrast agents
Blood pool contrast agents iron oxides (MION)
(typical 10 mg Fe/kg body)
Control
Stimulation
Vessel dilation
(concentration of Fe in a voxel increases)
Fe
Increase susceptibility effect Reduce MRI signals
Rosen et al., 1991 Mandeville et al., 1998
Kennan et al., 1998
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fMRI without and without MION
(Cat visual stimulation, 156 x156 x 1000 ?m)
(Zhao, Wang, Hendrich, Ugurbil Kim, Neuroimage,
30, 1149-60, 2006)
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?R2 ?(1/T2) -percent change/TE ?
CBVv(1 Y)
where
1 - Y CMRO2 / CBF

• Cerebral Oxygen Consumption Rate
• Cerebral Blood Flow
• Venous Blood Volume

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Task/stimulation
Neural activity
CBV
CBF
CMRo2
dHb
T2
T2
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CBV vs. CBF during Hypercapnia
(?-chloralose anesthetized rats)
rCBV (arbitrary unit)
rCBV 0.975rCBF0.40 (100 CBF -gt 31 CBV)
rCBV 0.31 rCBF 0.67 ( r 0.85 )
58 ml/100 g/min
rCBF (arbitrary unit)
Lee et al., MRM, 2001
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CBF vs. Arterial and Venous CBV
rCBV (vein)
rCBV (artery)
rCBV (arbitrary unit)
rCBF (arbitrary unit)
Lee et al., MRM, 2001
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Task/stimulation
Neural activity
CBV
CBF
CMRo2
dHb
T2
T2
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fMRI Signal Change is related to Neural Activity
LOGOTHETIS et al. Nature, 412, 150 157, 2001
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Spatial Frequency Dependence
Electrophysiology Recordings
0.15 cyc/deg
A set of six different moving gratings with
spatial frequencies ranging from 0.075 - 0.47
cyc/deg (2 cyc/s) were presented in a
pseudo-random fashion.
Movshon et al., 1978
Harel et al.
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Spatial Frequency Tuning Curve of BOLD fMRI
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fMRI Signal Change is related to Neural Activity
LOGOTHETIS et al. Nature, 412, 150 157, 2001
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Heterogeneity of fMRI changes in humans response
times
(Bilateral finger movements)
Relative Delay Time
2 sec
0 sec
- 2 sec
Provided by P.A. Bandettini
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Variability in the BOLD Response across subjects
Human V1 Area
BOLD Signal Change ()
Time (seconds)
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Visual Stimulation under different baseline
conditions
hypercapnia
hypocapnia
n 6 subjects for each study
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Interpretation of fMRI signals

• fMRI signal is an index of ensemble of neural
  activity
• (presumably monotonic relation)

• Neural source of BOLD signal is not clear
  spiking activities vs.
• synaptic activity, excitatory vs. inhibitory

• Difficulty to compare fMRI signals across
  cortical regions and subjects
• due to BOLD signal dependencies on vascular
  structure and volume.

- Excellent non-invasive tool to map whole brain
functions with relatively high spatial (a few
millimeters in humans) and temporal resolution
(a few seconds).
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Example 1 Visually-Instructed Four-Finger
Movements

• As soon as a circle is lit, the corresponding
  button is pushed.
• Tasks, consisting of four finger movements, are
  separated by one to several seconds.

Kim et al., Magn Reson Med, 1997
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fMRI Signal vs. Finger Movements
finger pressure
Delay time 3 7.5 s
BOLD change ()
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Example 2 mental rotation experiment
displayed until decision is made
time
Presentation
Contemplation
Decision
Richter et al. J. Cogn. Neurosci, 1999
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Functional Maps of Mental Rotation
Supplementary Motor Area
Central Sulcus
Superior Parietal Area
Lateral Premotor Area
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Response Time-locked Time Courses in M1 and SMA
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Primary motor
Relative fMRI intensity
Supplementary motor
-10
-5
0
5
10
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Time from button press (sec)