1. Perfusion-Based fMRI Thomas T
Perfusion-Based fMRI Thomas T. Liu Center for Functional MRI University of California San Diego May 7, 2006

2. Goal
To provide a basic understanding of the theory and application of arterial spin labeling in functional MRI.

3. Topics What is Cerebral Blood Flow? Arterial Spin Labeling
Data Processing
Applications

4. Cerebral blood flow (CBF) is a fundamental physiological quantity
Cerebral blood flow (CBF) is a fundamental physiological quantity. Closely related to brain function.
From C. Iadecola 2004

5. Cerebral Blood Flow (CBF)
CBF = Perfusion
= Rate of delivery of arterial blood to a
capillary bed in tissue.
Units:
(ml of Blood)
(100 grams of tissue)(minute)
Typical value is 60 ml/(100g-min) or
60 ml/(100 ml-min) = 0.01 s-1, assuming average density of brain equals 1 gm/ml

6. High CBF
Low CBF
Time

7. Bereczki et al 1992

8. Methods for Measuring CBF
Quantitative Autoradiography
Laser Doppler
Diffusible and Radioactive Tracer Based Methods
PET and SPECT
Contrast-Based MRI
Arterial Spin Labeling

9. Arterial spin labeling (ASL)
Tag by Magnetic Inversion 1:
Acquire image
Control 2:
Acquire image
The technique of arterial spin labeleing can be defined as follows. We first tag arterial blood prior to the imaging plan we then wait and aquire an image.
Control - Tag = M µ CBF

10. Flow-driven inversion Velocity-selective ASL
Imaging
Region
Pulsed ASL
Spatial inversion
Tag
Continuous ASL
Flow-driven inversion
Velocity-selective ASL
Velocity-dependent saturation
Mz(blood) M
control
tag t TI
Mz(blood) M
control
tag t TI

11. ASL Pulse Sequences Tag Control Acquire TI = Inversion Time TR
PASL/VSASL
Tag
Control
Acquire
Labeling Time
Post Labeling Delay
CASL

12. Conventional Pulsed ASL (PASL) off-resonance IR pulse
tag
imaging slice
control
presaturation slice
off-resonance IR pulse
EPISTAR
PICORE
FAIR
Courtesy of Wen-Ming Luh

13. Continuous ASL (CASL) B0 Amplitude Conventional Tag Modulated Control
Imaging
Plane
Blood
Magnetization
Inversion
Planes B0
Amplitude
Modulated
Control
Conventional
Control
Tag

14. Velocity Selective ASL (VSASL)
0.1
Velocity (cm/s)
Physiological
Motion 1 10 Mz {
Control
Tag
Image
Wong et al 2006

15. CASL
PASL
PASL
VSASL
Credit: E. Wong

16. ASL Signal Equation ∆M= CBF · Aeff
Mz(blood)
control M - = M
tag t t TI
∆M= CBF · Aeff
Aeff is the effective area of the arterial bolus. It depends on both physiology and pulse sequence parameters.

17. Quantitative ASL Goal: Make Aeff a well-controlled parameter
∆M= CBF · Aeff
Goal: Make Aeff a well-controlled parameter
that is robust to assumptions about
physiological parameters.

18. Major Sources of Error for ASL
Transit Delays
Bolus Width in PASL
Relaxation Effects - different relaxation rates for blood and tissue, time of exchange.
Intravascular signal -- blood destined to perfuse more
distal slices
Offset bias to due imperfect subtraction of static
tissue -- slice profiles, magnetization transfer effects

19. Transit Delays
CASL PASL
~ 3 cm
∆t < 1000ms
~ 1 cm
∆t < 700ms

20. Controlling for Transit Delays in CASL
Tagging Plane
A B
A B
time
Voxels A and B have the same CBF, but voxel B
will appear to have lower CBF if the measurement is
made too early. Proper selection of post-labeling delay is key

21. Amplifying Transit Delays Effects in CASL
Tagging Plane
Baseline Signal
Activation Signal
Baseline Signal
Activation Signal
time
Acquiring the signal at an earlier TI amplifies the difference between the activated state and the baseline state.

22. Arterial Bolus Width CASL PASL time Temporal Width of Baseline
bolus determined by
the pulse sequence
Baseline
Global flow
increase
PASL
Temporal Width of
bolus determined by
arterial velocity
and size of tagging
slab. Underestimates
global flow changes.
Baseline
Global flow
increase
time

23. Defining Bolus Width in PASL (QUIPSS II)
Saturate
spins still
in the slab
Baseline
Global flow
increase
Tag the
spins
TI1
Bolus temporal
width = TI1

24. QUIPSS II Modification
Tag
Control
Acquire
TI1
Saturation Pulses

25. Controlling for Transit Delays in PASL
Tagging Slab
A B
A B
TI1
TI2 > transit delay + TI1

26. Topics What is Cerebral Blood Flow? Arterial Spin Labeling
Data Processing
Applications

27. ASL Time Series Wait 1 +0.5 -0.5 -1 Perfusion Images Image 1 Image 2
Tag by Magnetic Inversion
Tag
Image 1
Control
Image 2
Tag by Magnetic Inversion
Tag
Image 3
Control
Image 4
-0.5 1
+0.5 -1
Perfusion Images

28. CBF and BOLD Time Series

30. Demodulate
Modulate

31. Modulate

32. Hernandez-Garcia et al 2005; Roller et al 2006, Abstract 540

33. Removing Physiological Noise
Modeling a fMRI signal using a General Linear Model (GLM) + =
Data
Physiological
Noise
Matrix
Additive
Gaussian
Noise
Nuisance
Matrix
Design
Matrix
To estimate the contribution of physiological noise to the fMRI signal, we can model our fmri signal as a General linear model
To estimate the contribution of X, S, and P to y, h, b, and c are estimated using least squares estimation.
RETROICOR assumes the physiological noise is additive, thus estimating c allows us to subtract Pc from y to get a noiseless image time series.
H-x*xinvxxy
In the following slides I will dexcribe how we model matrices X S and P
y = Xh Sb Pc n

34. Removing Physiological Noise
Perfusion time series: Before Correction (cc = 0.15)
Perfusion time series: After Correction (cc = 0.71)
Perfusion Time Series
Signal Intensity
Image Number (4 Hz)
In our methods, we have treated the Tag/Control time series as the signal of interest, but it is useful to see how our method corrects a perfusion time series since that is the signal that we care about.
Pulse Ox (finger)
Cardiac component
estimated in brain

35. Removing Physiological Noise
0.200
0.275
0.350
0.425
0.500
Young Subject
Older Subject
(b) Corrected
(a) Uncorrected
Corrected
(c)
(d)
(e)
In our methods, we have treated the Tag/Control time series as the signal of interest, but it is useful to see how our method corrects a perfusion time series since that is the signal that we care about.

36. Principal Components Based Correction
mRETROICOR
CompCor
Behzadi et al Abstract 235

37. Background Suppression
Tag
Acquire
QUIPSS II Saturation Pulse
Inversion Pulses
Pre-saturation
Pulse
200
400
600
800
1000
1200
1400 -1
-0.8
-0.6
-0.4
-0.2
0.2
0.4
0.6
0.8 1
time (ms) M z
Background Suppression with Double Inversion GM WM
CSF
Nulling of static tissue element

38. Background Suppression
Visual Study Results
St. Lawrence et al 2005
Behzadi et al Abstract 3295

39. Single Shot Perfusion Labeling (SSPL)
From JA Duyn et al, MRM 2001

40. Single Shot Perfusion Labeling (SSPL)
From JA Duyn et al, MRM 2001

41. Topics What is Cerebral Blood Flow? Arterial Spin Labeling
Data Processing
Applications

42. Applications of ASL
Quantitative Measures of both baseline and functional CBF
Multimodal measures of CBF, BOLD, (and CBV) to estimate functional changes in oxygen metabolism.
Experiments with long task periods
Mapping of functional activity.

43. Baseline CBF Modulates the BOLD Response

44. Effect of Baseline CBF on BOLD Response

45. Effect of Acetazolamide on BOLD and CBF
Percent BOLD Changes
CBF Changes
Brown et al 2003

46. Effect of Hypercapnia on BOLD and CBF
Stefanovic et al 2006

47. Applications of ASL
Quantitative Measures of both baseline and functional CBF
Multimodal measures of CBF, BOLD, (and CBV) to estimate functional changes in oxygen metabolism.
Experiments with long task periods
Mapping of functional activity.

48. BOLD Dynamics CMRO2 Stimulus ATP ADP BOLD Neural CBF Signal Activity
CMRGlc
CBF
CMRO2
CBV
BOLD
Signal
NO, K+
CO2
Lac
Credit: Rick Buxton

49. Effect of Age on CBF and BOLD Responses in the Hippocampus
Restom et al, Abstract 377

50. Estimation of CMRO2 Changes with Combined CBF and BOLD measures
Hypercapnia
Contralateral
Ipsilateral
Stefanovic et al 2004

51. Simultaneous measure of CBF, BOLD, and VASO (CBV)
Yang et al 2004
VASO
CBF
BOLD

52. Bayesian Analysis of dual -echo ASL data (Woolrich et al. Abstract 538)
TE=9 msecs
TE=30 msecs
data
model fit
static
delivered blood

53. Bayesian Analysis of ASL data (Woolrich et al. Abstract 538)
CBF
static magnetisation, M

54. Applications of ASL
Quantitative Measures of both baseline and functional CBF
Multimodal measures of CBF, BOLD, (and CBV) to estimate functional changes in oxygen metabolism.
Experiments with long task periods
Mapping of functional activity.

56. ASL with very low task frequencies - Wang et al., MRM 2003

57. ASL Imaging of Stress- Wang et al., PNAS 2005

58. ASL Imaging of Natural Vision; Rao et al, Abstract 167
CBF and BOLD activations during viewing of Road Runner “Gee W-h-I-z-z-z-z-z-z” Cartoon

59. Applications of ASL
Quantitative Measures of both baseline and functional CBF
Multimodal measures of CBF, BOLD, (and CBV) to estimate functional changes in oxygen metabolism.
Experiments with long task periods
Mapping of functional activity.

60. ASL Mapping of Cortical Columns in Cat Visual Cortex
Duong et al, PNAS, 2001.
FAIR sequence, TI = 1500 ms, TR 3000 ms

61. Z. Liu and X. Hu, Abstract 891

62. Summary
Arterial spin labeling can provide non-invasive quantitative measures of baseline and functional CBF.
2. Since CBF is a well-defined physiological quantity, measures of CBF can be used to improve the interpretation of fMRI studies, especially for clinical populations.
3. The combination of CBF measures with BOLD (and CBV) measures can be used to estimate changes in oxygen metabolism.

63. Acknowledgements Yashar Behzadi Rick Buxton Wen-Ming Luh
Joanna Perthen
Khaled Restom
Eric Roller
Mark Woolrich
Eric Wong