Spatial, Temporal, and Interpretive Limits of Functional MRI

1. Spatial, Temporal, and Interpretive Limits of Functional MRI Peter A. Bandettini, Ph.D Unit on Functional Imaging Methods & 3T Neuroimaging Core Facility Laboratory of Brain and Cognition National Institute of Mental Health

2. time Anatomic Functional

3. Echo-Planar Imaging

4. Single Shot Imaging T2* decay EPI Readout Window ≈ 20 to 40 ms

5. 1991-1992 1992-1999

6. Imaging System Components Magnet RF Receiver Viewing Console X Y Z RF Transmitter Scan Controller Gradient Power Systems

7. 2 G/cm, 350 T/m/s 4 G/cm, 150 T/m/s 10 G/cm, 1000 T/m/s

8. The use of fMRI to Investigate Brain Function Where? When? How much? --- How to get the brain to do what we want it to do in the context of an fMRI experiment?

9. A Primary Challenge: ...to make progressively more precise inferences using fMRI without making too many assumptions about non-neuronal physiologic factors.

10. Contrast in FMRI Hemodynamic Specificity • The Hemodynamic Transfer Function Location, Latency, Magnitude • Best Results So Far Temporal Resolution, Spatial Resolution • Neuronal Activation Input Strategies Block Design Phase and Frequency Encoding Orthogonal Designs Parametric Designs Event-Related Designs Free Behavior Designs

11. Contrast in FMRI Hemodynamic Specificity • The Hemodynamic Transfer Function Location, Latency, Magnitude • Best Results So Far Temporal Resolution, Spatial Resolution • Neuronal Activation Input Strategies Block Design Phase and Frequency Encoding Orthogonal Designs Parametric Designs Event-Related Designs Free Behavior Designs

12. Contrast in Functional MRI • Blood Volume • Contrast agent injection and time series collection of T2* or T2 - weighted images • BOLD • Time series collection of T2* or T2 - weighted images • Perfusion • T1 weighting • Arterial spin labeling • CMRO2 • BOLD and Perfusion w/ Normalization to Global Perfusion Change

13. RestingActive

15. Faster Slower

16. BOLD Contrast in the Detection of Neuronal Activity Cerebral Tissue Activation Local Vasodilation Oxygen Delivery Exceeds Metabolic Need Increase in Cerebral Blood Flow and Volume Increase in Capillary and Venous Blood Oxygenation Deoxy-hemoglobin: paramagnetic Oxy-hemoglobin: diamagnetic Decrease in Deoxy-hemoglobin Decrease in susceptibility-related intravoxel dephasing Increase in T2 and T2* Local Signal Increase in T2 and T2* - weighted sequences

17. The BOLD Signal Blood Oxygenation Level Dependent (BOLD) signal changes task task

18. Alternating Left and Right Finger Tapping ~1992

19. Creating a Functional Image ON ON ON ON ON X Signal Time Course Reference Function =

20. Cross Correlation Image Cross Correlation Image Anatomical Image

22. Perfusion / Flow Imaging EPISTAR FAIR . . . - - - - Perfusion Time Series . . .

23. TI (ms) 200 400 600 800 1000 1200 FAIR EPISTAR

24. Resting ASL Signal

25. Comparison with Positron Emission Tomography PET: H215O MRI: ASL

26. Perfusion Rest Activation BOLD

27. Anatomy BOLD Perfusion

28. Hemdodynamic Stress Calibration 5% CO2 12% O2

29. 20 3 15 2 10 BOLD (% increase) CBF (% increase) 5 1 0 0 -5 -10 0 200 400 600 800 1000 1200 1400 0 200 400 600 800 1000 1200 1400 Time (seconds) Time (seconds) hypercapnia visual stimulation Hoge, et al. CMRO2-related BOLD signal deficit: CBF BOLD Simultaneous Perfusion and BOLD imaging during graded visual activation and hypercapnia N=12

30. 4 +10 +20 -10 0 25 3 20 15 CMRO2 (% increase) BOLD (% increase) 2 10 5 1 0 0 10 20 30 40 50 Perfusion (% increase) 0 0 10 20 30 40 50 Perfusion (% increase) Hoge, et al. CBF-CMRO2 coupling Characterizing Activation-induced CMRO2 changes using calibration with hypercapnia

31. Hoge, et al. Computed CMRO2 changes 40 30 20 10 0 % % -10 -20 -30 -40 Subject 2 Subject 1

32. Hemodynamic Specificity Arterial inflow (BOLD TR < 500 ms) Venous inflow (Perf. No VN)

33. A little bit about the “noise”

34. Temporal vs. Spatial SNR- 3T 26ms 49ms 26ms 49ms SPIRAL 27ms 50ms 27ms 50ms EPI

35. 0.25 Hz Breathing at 3T 3ms Image 26ms Respiration map Power Spectra 49ms 0 0.25 0.5 Hz

36. 0.68 Hz Cardiac rate at 3T 3ms Image 26ms Power Spectra Cardiac map 49ms 0 0.68 (aliased) 0.5 Hz

37. 1000 800 600 400 200 0 200 400 600 800 1000 Temporal S/N vs. Image S/N PHANTOMS SUBJECTS 1400 1200 1000 800 600 400 200 Temporal S/N Temporal S/N 0 200 400 600 800 1000 1200 1400 Image S/N Image S/N N. Petridou

38. CC Histogram Continuously Growing Activation Area Inflection Point Ziad Saad, et al

39. Contrast in FMRI Hemodynamic Specificity • The Hemodynamic Transfer Function Location, Latency, Magnitude, Linearity • Best Results So Far Temporal Resolution, Spatial Resolution • Neuronal Activation Input Strategies Block Design Phase and Frequency Encoding Orthogonal Designs Parametric Designs Event-Related Designs Free Behavior Designs

40. Hemodynamic Transfer Function Neuronal Measured Activation fMRI Signal Hemodynamics Physiolologic Factors

42. 2 1000 msec 1.5 100 msec 34 msec 1 0.5 0 -0.5 -1 15 20 25 30 35 Time (sec)

44. + 2 sec Latency - 2 sec Magnitude

45. Observed Responses measured ideal (linear) visual stimulation 250 ms 500 ms 1000 ms 2000 ms motor task 500 ms 1000 ms 2000 ms 4000 ms

46. 20 s 2000 ms 1000 ms 500 ms 250 ms 0 10 20 30 40 0 10 20 30 40 BOLD response is nonlinear Observed response Linear response Short duration stimuli produce larger responses than expected

47. 8 f (SD) 6 4 2 0 10 20 30 40 0 1 2 3 4 5 0 10 20 30 40 Stimulus Duration -2 8 f (SD) 6 60 4 40 2 20 0 1 2 3 4 5 0 2 0 2 4 6 8 Stimulus Duration -2 nonlinearity Results – visual task

48. Results – visual task Nonlinearity Magnitude Latency

49. 8 f (SD) 6 4 2 60 0 10 20 30 40 0 10 20 30 40 40 0 1 2 3 4 5 Stimulus Duration 20 0 2 0 2 4 6 8 nonlinearity Results – motor task 8 f (SD) 6 4 2 0 1 2 3 4 5 Stimulus Duration

50. Results – motor task Nonlinearity Magnitude Latency