Latest Developments in fMRI

1. Latest Developments in fMRI 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. The use of fMRI for the Investigation of Brain Function and Physiology • Where? • When? • How much? • How to get the brain to do what we want it to • do in the context of an fMRI experiment? • (limitations: limited time and signal to noise, motion, acoustic noise) • How much more information can we obtain?

3. Neuronal Measured Activation fMRI Signal ? ? Hemodynamics Physiologic Factors

4. A Primary Challenge for Observing Brain Activation: ...to make progressively more precise inferences without making too many assumptions about non-neuronal physiologic factors.

5. 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

6. RestingActive

9. 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

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

11. Alternating Left and Right Finger Tapping ~1992

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

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

15. Resting ASL Signal

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

17. Pushingthe Envelope… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

18. Pushingthe Envelope… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

19. time Anatomic Functional

20. Echo-Planar Imaging

22. 2 1000 msec 1.5 100 msec 34 msec 1 0.5 0 -0.5 -1 15 20 25 30 35 Time (sec)

24. Word stem completion

26. + 2 sec Latency - 2 sec Magnitude

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

28. 9.0 seconds 15 seconds 500 msec 500 msec 20 30 10 Time (seconds)

29. 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)

30. 500 ms 500 ms RightHemifield Left Hemifield + 2.5 s - = 0 s - 2.5 s

31. 11026–11031 PNAS September 26, 2000vol. 97 no. 20

32. Pushingthe Envelope… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

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

34. T2* decay EPI Window 1 Multishot Imaging T2* decay EPI Window 2

35. T2* decay EPI Window Partial k-space imaging

36. Multi Shot EPI Excitations 1 2 4 8 Matrix Size 64 x 64 128 x 128 256 x 128 256 x 256

40. Perfusion Rest Activation BOLD

41. Anatomy BOLD Perfusion

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

43. ODC Maps using fMRI 1 cm calcarine • Identical in size, orientation, and appearance to those obtained by optical imaging1 and histology3,4. 1Malonek D, Grinvald A. Science 272, 551-4 (1996). 3Horton JC, Hocking DR. J Neurosci 16, 7228-39 (1996). 4Horton JC, et al. Arch Ophthalmol 108, 1025-31 (1990).

44. Why short is better than long It is argued that fMRI cannot achieve submillimeter functional resolution because a saturated hyperoxic vascular response to neural activity spreads over many millimeters1,2. However, optical imaging has demonstrated that the hyperoxic response can yield well-localized maps when using short duration stimuli (<5 sec)1. The vascular response to prolonged neural stimulation [Oxy] ~12 sec The vascular response to brief neural stimulation 1Malonek D, Grinvald A. Science 272, 551-4 (1996). 2Kim D-S, Duong T, Kim S-G. Nat Neurosci 3, 164-9 (2000).

45. Pushingthe Envelope… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

46. 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

48. Pushingthe Envelope… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

49. Motor Cortex Auditory Cortex

50. time (s) Different stimulus “ON” periods measured linear BOLD Response Signal Stimulus timing 0.25 s 0.5 s 1 s 2 s 20 s Brief stimuli produce larger responses than expected