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Goal

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  1. Perfusion-Based fMRIThomas T. LiuCenter for Functional MRIUniversity of California San DiegoMay 19, 2007

  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. Closely related to brain function. From C. Iadecola 2004

  5. (ml of Blood) Units: (100 grams of tissue)(minute) Cerebral Blood Flow (CBF) CBF = Perfusion = Rate of delivery of arterial blood to a capillary bed in tissue. 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. 1: Tag by Magnetic Inversion Acquire image 2: Control Control - Tag = M µ CBF Acquire image Arterial spin labeling (ASL)

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

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

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

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

  14. Velocity Selective ASL (VSASL) 1 Control Mz Image { Tag 0 0.1 1 10 Physiological Motion Velocity (cm/s) Wong et al 2006

  15. CASL PASL PASL VSASL Credit: E. Wong

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

  17. Quantitative ASL ∆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. PASL CASL ~ 3 cm ∆t < 1000ms ~ 1 cm ∆t < 700ms Transit Delays

  20. A B A B Controlling for Transit Delays in CASL Tagging Plane 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 Temporal Width of bolus determined by the pulse sequence Baseline Global flow increase Temporal Width of bolus determined by arterial velocity and size of tagging slab. Underestimates global flow changes. PASL Baseline Global flow increase time

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

  24. Tag Saturate Acquire Control Acquire TI1 TI1 TI2 TI2 QUIPSS II Modification

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

  28. CBF and BOLD Time Series

  29. Mumford et al 2006

  30. + + + + + Removing Physiological Noise Modeling a fMRI signal using a General Linear Model (GLM) = Data Additive Gaussian Noise Physiological Noise Matrix Nuisance Matrix Design Matrix y = Xh + Sb + Pc + n

  31. Perfusion Time Series Perfusion time series: Before Correction (cc = 0.15) Perfusion time series: After Correction (cc = 0.71) Removing Physiological Noise Signal Intensity Image Number (4 Hz) Pulse Ox (finger) Cardiac component estimated in brain

  32. Impact of Physiological Noise on ASL Data

  33. Principal Components Analysis Component Based Approaches Gray Matter T1 Weighted Anatomical CSF Segment into tissue types White Matter Tissue Partial Volume Maps

  34. + + + + + = Stimulus Response Constant DC Term Linear Trend White matter and CSF principal components Gaussian Noise fMRI signal y = Xh + Sb + Pestc + n Component Based Noise Correction (CompCor)

  35. Principal Components Based Correction mRETROICOR CompCor Behzadi et al (In press)

  36. Background Suppression with Double Inversion 1 GM 0.8 WM CSF 0.6 0.4 0.2 z 0 M -0.2 -0.4 -0.6 -0.8 -1 0 200 400 600 800 1000 1200 1400 time (ms) Nulling of static tissue element Background Suppression St. Lawrence et al 2005

  37. Background Suppression St. Lawrence et al 2005

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

  39. 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.

  40. Baseline CBF Modulates the BOLD Response

  41. Baseline CBF Modulates the BOLD Response Lu et al, Abstract 613, ISMRM 2007

  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. ASL Signal Cerebral Blood Volume Cerebral Blood Flow BOLD Signal Metabolism (CMRO2) deoxyHb Neural Activity

  44. Effect of Age on CBF and BOLD Responses in the Hippocampus Restom et al 2007, In press

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

  46. 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.

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

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