1. BOLD functional MRI
Magnetic properties of oxyhemoglobin and deoxyhemoglobin
L. Pauling and C. Coryell, PNAS USA 22: (1936)
BOLD effects in vivo
S. Ogawa, et al., MRM, 14:68-78 (1990)
BOLD activation experiments
K. K. Kwong, et al., PNAS USA, 89: (1992)
S. Ogawa, et al., PNAS USA, 89: (1992)
P. A. Bandettini, et al., MRM, 25: (1992)
J. Frahm, et al., JMRI, 2: (1992)

2. Mechanism of BOLD Functional MRI
Brain activity
Oxygen consumption
Cerebral blood flow
Oxyhemoglobin
Deoxyhemoglobin
Magnetic susceptibility
T2*
MRI signal intesity

3. Magnetic Properties of Oxyhemoglobin and Deoxyhemoglobin
Deoxyhemoglobin: paramagnetic (c > 0)
paramagnetic with respect to the surrounding tissue
Oxyhemoglobin: diamagnetic (c < 0)
isomagnetic with respect to the surrounding tissue

4. Magnetic Susceptibility

5. Oxyhemoglobin and Deoxyhemoglobin in Veins during Brain Activation
Rest
Activation
Normal blood flow
High blood flow
Oxyhemoglobin Deoxyhemoglobin

6. T2* Effect in fMRI
action
MR signal (S)
rest TE t
excitation
reception

7. Time Series and Activation Maps
Signal Intensity
Off On
Off On
Off On
Off On
Scan Number

8. Challenges in Functional FMRI
Sensitivity (Contrast-to-noise ratio)
BOLD signal change is ~1-2% at 1.5 T; signal-to-noise ratio in single-shot EPI images is ~100.
Physiological pulsations (cardiac and respiratory); Head motion; instrumental instability
Specificity
Location of activation – neurons or veins
Susceptibility artifacts

9. Challenges in Functional FMRI
Temporal resolution
Limited by BOLD impulse-response function, image sampling rate, and spin relaxation times
Spatial resolution
Limited by BOLD point-spread function, signal-to-noise ratio, and image sampling rate
Non-linearity
Neurological and hemodynamic
Acoustic noise

10. Contrast-to-Noise Ratio
Brain Activation-related signal change
Sensitivity =
Temporal fluctuation of image intensity

11. Enhancement of BOLD Contrast
Higher magnetic fields
BOLD signal change DS ~ Ba (1 < a < 2)
Standard clinical MRI scanner at 1.5 T
Research scanner up to 8 T currently
Optimization of image acquisition parameters
Optimal echo time (TE) to maximize BOLD signal
Optimal repetition time (TR) to increase number of images acquired per unit time, and to decrease motion artifacts

12. TE Dependence of Signal Change

13. Suppression of Temporal Fluctuations
Head motion reduction
Head holder modified from a football helmet
Image realignment in data processing
Physiological pulsations
Correction using simultaneously recorded cardiac and respiratory signals
Ultra-fast imaging techniques
Single-shot echo-planner imaging (EPI)
Single-shot Spiral imaging
Post-processing
Denoising

14. Ultra-Fast Spiral Scanning
An image (64x64) can be acquired in ~ 20 ms
Reduce head motion
Increase number of images collected per unit time
Stable
Spiral trajectory is insensitive to motion and flow artifacts
Zero gradient moments at the center of k-space (self-navigated)
First-order gradient moments vary smoothly over k-space

15. Multi-Slice Spiral Images

16. Multi-Slice EPI Images

17. Activation Maps on Anatomical ImagesMS
Spiral MS
EPI 3D
Spiral

18. Histograms of Temporal Standard Deviations80 60 40 20
MS-Spiral
MS-EPI
3D-Spiral
Number of Activated Voxels
SD/Mean

19. Comparison of Activation Studies Using MS-spiral, MS-EPI, and 3D-spiral

20. Specificity in fMRI Inflow Effects
Generated by fresh (fully recovered) spins moving into the region excited under saturating conditions
Flow change in large vessels can lead to substantial signal increases (20-30%), and compromise spatial accuracy in activation studies

21. Inflow Effects in fMRI Suppression of inflowing spins a bd b
Suppression of
inflowing spins
No suppression of inflowing spins

22. Gradient Echo vs. Spin Echo in fMRI
Diameter (mm)
DR2, DR2 * (1/sec) 20 10
DR2
DR2*
Contribution of large vessels and capillary beds to the BOLD signals;
Separation/suppression of signals from large vessels.

23. Temporal resolution
Impulse-response function
12s 5s 2s t

24. Temporal resolution Sampling rate (single-shot EPI ~10-15 slices/sec)
Whole brain (~30 4mm-slices): 2-3 sec
T1 relaxation times
Grey matter: 1 sec
White matter: 0.8 sec
CSF: 2-3 sec

25. Spatial resolution BOLD point-spread function Image spatial resolution
Spatial extent of neuronal activity, CBF, and BOLD
Image spatial resolution
64x64 with FOV 240 mm: 3.75mm
128x128 with FOV 240 mm: mm
Signal-to-noise ration
Single-shot EPI with voxel size 4x4x4 mm3: ~100

26. Non-linearity of BOLD Response
BOLD response vs. length of stimulation t 2t
BOLD response during rapidly-repeated stimulation ts

27. Experimental Designs in fMRI
Block-Design fMRI
Task
Rest
20-60s
Event-Related fMRI
8-12s

28. Hemodynamic Response vs. ISI5 10 15
Time (sec)
Signal Changes (%)
1.00
1.01
ISI=8s
ISI=12s
ISI=16s

29. Visual Activation Maps (ISI=12s)

30. Data Analysis Methods For fMRI
Hypothesis-driven approaches
t-test, cross-correlation, GLM, etc.
Data-driven approaches
Principal component analysis (PCA), independent component analysis (ICA), and clustering analysis.