fMRI Contrast: How Much More Information Can We Obtain?

1. fMRI Contrast: How Much More Information Can We Obtain? 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. BOLD Contrast

3. Neuronal Measured Activation fMRI Signal ? ? Hemodynamics The continuing challenge is to make progressively more precise neuronal, metabolic, and hemodynamic inferences across spatial and temporal scales.

4. Pulse Sequence Modulation Task Modulation & Measurement Neuronal Measured Activation fMRI Signal ? ? Hemodynamics Physiologic Modulation / Measurement

5. 1991- 2 • TE dependence • Field Strength Dependence • Resolution Dependence • Pulse sequence dependence (T2 and T2*) • Dynamics: latency and return to baseline • First BOLD models • Correlation of BOLD with parametric task manipulation • Post undershoot • NMR phase shift observation • Angio and venogram correlation • Effects of Physiologic Stress • Retinotopy • Cognitive mapping • Event - related fMRI • Parametric task design • Sub-millimeter resolution fMRI • Diffusion weighting dependence (IV contribution) • Physiologic fluctuations • Extended duration stimulation effects • Pre undershoot • Flow and BOLD comparisons (dynamics and magnitude) • Blood volume dynamics • Simultaneous flow and BOLD acquisition • Ocular Dominance Column Mapping • CMRO2 Mapping • Randomized ER-fMRI task design • Balloon Model • Baseline Blood Oxygenation Quantitation • Mental Chronomitry • Linearity of BOLD signal change BOLD Contrast Advancements 1992- 3 1993- 4 1994 - 5 1995 - 6 1996 - 7 1997- 8 1998 - 9 1999 - 2000

6. Pulse Sequence Modulation Task Modulation & Measurement Neuronal Measured Activation fMRI Signal ? ? Hemodynamics Physiologic Modulation / Measurement

7. + 2 sec Latency - 2 sec Magnitude

8. 9.0 seconds 15 seconds 500 msec 500 msec 20 30 10 Time (seconds)

9. Regions of Interest Used for Hemi-Field Experiment Left Hemisphere Right Hemisphere

10. 3.2 2.4 1.6 0.8 0 -0.8 -1.6 -2.4 0 10 20 30 Hemi-field with 500 msec asynchrony Average of 6 runs Standard Deviations Shown Percent MR Signal Strength Time (seconds)

11. 500 ms 500 ms RightHemifield Left Hemifield + 2.5 s - = 0 s - 2.5 s

12. Motor Cortex Auditory Cortex

14. Methods Motor Visual Stimulus Duration (SD) … SD = 500 ms SD = 250 ms … SD = 1000 ms SD = 500 ms … SD = 2000 ms SD = 1000 ms … SD = 4000 ms SD = 2000 ms 16 s … Blocked Trial 20 s

15. 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

16. a t Compute nonlinearity (for each voxel) • Amplitude of Response Fit ideal (linear) to response • Area under response / Stimulus Duration Output Area / Input Area

17. 6 6 4 f (SD) 4 f (SD) 2 2 0 1 2 3 4 5 0 1 2 3 4 5 Stimulus Duration Stimulus Duration 6 5 4 4 3 2 2 1 0 1 2 3 4 5 0 1 2 3 4 5 Nonlinearity Visual Motor Magnitude linear Area Output / input Output / input Stimulus Duration Stimulus Duration

18. Measure of Nonlinearity • Area under nonlinearity curve f (SD) Area 1 0 1 2 3 4 5 Stimulus Duration (s) • Slope of nonlinearity curve • difference at each SD

19. Results – visual task Nonlinearity Magnitude Latency

20. 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

21. Results – motor task Nonlinearity Magnitude Latency

22. 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

23. Reproducibility Visual task Motor task Nonlinearity1 Nonlinearity1 Nonlinearity2 Nonlinearity2 Experiment 1 Experiment 2 Experiment 1 Experiment 2

24. Conclusions • Responses to short duration stimuli are larger than predicted from a linear system • Spatial variation in this nonlinear relationship is seen • The variation in nonlinearity is not significantly correlated with magnitude or latency

25. Pulse Sequence Modulation Task Modulation & Measurement Neuronal Measured Activation fMRI Signal ? ? Hemodynamics Physiologic Modulation / Measurement

27. Finger Movement Anatomical 12% O2 5% CO2

29. % =

30. Pulse Sequence Modulation Task Modulation & Measurement Neuronal Measured Activation fMRI Signal ? ? Hemodynamics Physiologic Modulation / Measurement

31. Activation-induced MR Signal Change Mechanisms T1 Inflow T2 T2*

33. T1 - weighted T2* weighted T1 and T2* weighted

34. Perfusion Rest Activation BOLD

35. Anatomy BOLD Perfusion

36. Velocity Nulling at 1.5T

37. b = 0 b = 10 b = 50 b = 160

39.  = 6  =12  = 24  = 48 Wright et al. JMRI, 1: 275-228, 1991

40. D = 1 µm2 / ms -> 2.5 µm2 / ms  = 6  =12  = 24  = 48

42. Field -Strength Dependence of T2* and T2 Hct = 44,= 48, %HbO2 = 60, T2o = 250 ms, T2’ = 120 ms

43. Gradient-echo, %HbO2 = 60

44. Spin-echo, %HbO2 = 60

45. 3T Spin-Echo TE = 105 ms TR = ∞ Gradient-Echo TE = 50 ms Gradient-Echo functional TE = 50 ms Spin-Echo functional TE = 105 ms

46. Spin echo vs. Gradient echo compartment radius: < 3 µm 3 to 15 µm > 15 µm

47. ∆R2* / ∆R2 1.5 1.5 intravascular 1.5 to 3 extravascular 1.5 intravascular 3 to ∞ extravascular average ∆R2* / ∆R2 ≈ 3 to 4

50. Spin - Echo Gradient - Echo During Activation Increase Post Activation Undershoot