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. Technology Interpretation Methodology Applications

3. Methodology InterpretationApplications Technology Physicists Statisticians Mathematicians Physiologists Neuroscientists Clinicians Engineers

4. 3602010099989796959493929190898882 Methodology Hemoglobin Blood T2 IVIM Baseline Volume Interpretation Applications  Volume-V1 BOLD Correlation Analysis Linear Regression Event-related BOLD -V1, M1, A1 TE dep Veins IV vs EV BOLD models ASL Deconvolution Phase Mapping V1, V2..mapping Language Memory Presurgical Attention PSF of BOLD Pre-undershoot Ocular Dominance Mental Chronometry Electrophys. correlation 1.5T,3T, 4T 7T SE vs. GE Performance prediction Emotion Real time fMRI Balloon Model Post-undershoot Inflow PET correlation CO 2 effect CO 2 Calibration Drug effects Optical Im. Correlation Imagery Clinical Populations Plasticity Complex motor Motor learning Venography Face recognition Children Simultaneous ASL and BOLD Surface Mapping Linearity Mg + Dynamic IV volume B o dep. Diff. tensor Volume - Stroke Z-shim Free-behavior Designs Extended Stim. Local Human Head Gradient Coils NIRS Correlation SENSE Baseline Susceptibility Metab. Correlation Fluctuations Priming/Learning Resolution Dep. Tumor vasc. Technology EPI on Clin. Syst. EPI Quant. ASL Multi-shot fMRI Parametric Design Current Imaging? Multi-Modal Mapping Nav. pulses Motion Correction MRI Spiral EPI ASL vs. BOLD >8 channels Multi-variate Mapping ICA Fuzzy Clustering

5. Alternating Left and Right Finger Tapping ~ 1992

7. The use of fMRI for the Investigation of Brain Function and Physiology Where? When? How much? How to do it well? Is there more?

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

9. Neuronal Activation Hemodynamics Measured Signal Noise ?? ?

10. Latest Developments… 1.Temporal Resolution 2.Spatial Resolution 3.Sensitivity and Noise 4.Information Content 5.Implementation

11. Latest Developments… 1.Temporal Resolution 2.Spatial Resolution 3.Sensitivity and Noise 4.Information Content 5.Implementation

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

13. P. A. Bandettini, Functional MRI temporal resolution in "Functional MRI" (C. Moonen, and P. Bandettini., Eds.), p. 205-220, Springer - Verlag,. 1999.

15. Latency Magnitude + 2 sec - 2 sec P. A. Bandettini, The temporal resolution of Functional MRI in "Functional MRI" (C. Moonen, and P. Bandettini., Eds.), p. 205-220, Springer - Verlag,. 1999.

16. Venogram (3 Tesla)

18. Hemi-Field Experiment Right Hemisphere Left Hemisphere 10 2030 Time (seconds) 9.0 seconds 15 seconds 500 msec

19. = + 2.5 s - 2.5 s 0 s 500 ms Right Hemifield Left Hemifield - 0102030

20. Bottleneck In Processing (upstream) Delayed Processing (downstream) Hemodynamic Response Modulation

21. 11026–11031 PNAS September 26, 2000 vol. 97 no. 20

22. Latest Developments… 1.Temporal Resolution 2.Spatial Resolution 3.Sensitivity and Noise 4.Information Content 5.Implementation

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

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

25. Jesmanowicz, P. A. Bandettini, J. S. Hyde, (1998) “Single shot half k-space high resolution EPI for fMRI at 3T.” Magn. Reson. Med. 40, 754-762. Partial k-space imaging

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

27. Excitations1248 Matrix Size64 x 64128 x 128256 x 128 256 x 256 Multi Shot EPI

28. BOLD RestActivation P. A. Bandettini, E. C. Wong, Magnetic resonance imaging of human brain function: principles, practicalities, and possibilities, in "Neurosurgery Clinics of North America: Functional Imaging" (M. Haglund, Ed.), p.345-371, W. B. Saunders Co., 1997. Perfusion

29. Anatomy BOLD Perfusion P. A. Bandettini, E. C. Wong, Magnetic resonance imaging of human brain function: principles, practicalities, and possibilities, in "Neurosurgery Clinics of North America: Functional Imaging" (M. Haglund, Ed.), p.345-371, W. B. Saunders Co., 1997.

30. Venous inflow (for ASL, w/ no VN) Arterial inflow (BOLD TR < 500 ms) Pulse Sequence Sensitivity Spatial Heterogeneity

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

32. Latest Developments… 1.Temporal Resolution 2.Spatial Resolution 3.Sensitivity and Noise 4.Information Content 5.Implementation

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

34. 1400 1200 1000 800 600 400 200 0 200 400 600 800 1000 1200 1400 PHANTOMS Image S/N Temporal S/N N. Petridou Image S/N 0 200 400 600 800 1000 1000 800 600 400 200 Temporal S/N SUBJECTS Temporal S/N vs. Image S/N

35. Signal / Thermal Noise Signal / Physiologic Noise Resolution, Speed, Surface Coils, Field Strength, etc.. Optimal for fMRI Signal to Noise Ratio

36. Latest Developments… 1.Temporal Resolution 2.Spatial Resolution 3.Sensitivity and Noise 4.Information Content 5.Implementation

37.  Neuronal Activity Number of Neurons Spiking Rate Local Field Potential  Metabolism  Hemodynamics Blood Volume Flow Velocity Aerobic Metabolism Anaerobic Metabolism  BOLD Contrast - - Spiking Coherence  Deoxy-Hb Oxygenated Blood Deoxygenated Blood + MRI Pulse Sequence Perfusion  Perfusion Contrast  Inflow Contrast

38. Motor Cortex Auditory Cortex S. M. Rao et al, (1996) “Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex.” J. Cereb. Blood Flow and Met. 16, 1250-1254. J. R. Binder, et al, (1994). “Effects of stimulus rate on signal response during functional magnetic resonance imaging of auditory cortex.” Cogn. Brain Res. 2, 31-38

39. Logothetis et al. (2001) “Neurophysiological investigation of the basis of the fMRI signal” Nature, 412, 150-157 S. M. Rao et al, (1996) “Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex.” J. Cereb. Blood Flow and Met. 16, 1250-1254.

40. Different stimulus “ON” periods measured linear Signal 0.25 s0.5 s1 s2 s20 s time (s) Stimulus timing BOLD Response Brief stimuli produce larger responses than expected

41. Results – visual task 012345 -2 2 4 6 8 Stimulus Duration f (SD) 012345 -2 2 4 6 8 Stimulus Duration f (SD) 010203040 010203040

42. Results – visual task Nonlinearity Magnitude Latency

43. Sources of this Nonlinearity Neuronal Hemodynamic –Oxygen extraction –Blood volume dynamics  Volume Flow InFlow Out Oxygen Extraction

44. BOLD Correlation with Neuronal Activity Logothetis et al. (2001) “Neurophysiological investigation of the basis of the fMRI signal” Nature, 412, 150-157. P. A. Bandettini and L. G. Ungerleider, (2001) “From neuron to BOLD: new connections.” Nature Neuroscience, 4: 864-866.

45. 0200400600800100012001400 -10 -5 0 5 10 15 20 CBF (% increase) Time (seconds) 0200400600800100012001400 0 1 2 3 BOLD (% increase) Time (seconds) N=12 CBFBOLD Simultaneous Perfusion and BOLD imaging during graded visual activation and hypercapnia

46. Computed CMRO 2 Changes Subject 1 Subject 2 % 40 0 10 20 30 -10 -20 -30 -40

47. CBFOEFCMRO 2

48. Latest Developments… 1.Temporal Resolution 2.Spatial Resolution 3.Sensitivity and Noise 4.Information Content 5.Implementation

49. Neuronal Activation Input Strategies 1.Block Design 2. Parametric Design 3. Frequency Encoding 4. Phase Encoding 5. Event Related 6. Orthogonal Design 7. Free Behavior Design

50. Blamire, A. M., et al. (1992). “Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging.” Proc. Natl. Acad. Sci. USA 89: 11069-11073. First Event-related fMRI Results

51. Event Related Advantages Task Randomization Post acquisition, Performance-based, data binning Natural presentation Reduction of habituation effects Overt responses Reduction of scanner noise effects More precise estimation of hemodynamic response

52. fMRI during tasks that involve brief motion motion BOLD response task BOLD response t motion task Blocked Design Event-Related Design R. M. Birn, P. A. Bandettini, R. W. Cox, R. Shaker, Event - related fMRI of tasks involving brief motion. Human Brain Mapping 7: 106-114 (1999).

53. 234 5 678 9 101112 13 Overt Word Production R. M. Birn, P. A. Bandettini, R. W. Cox, R. Shaker, Event - related fMRI of tasks involving brief motion. Human Brain Mapping 7: 106-114 (1999).

54. Speaking - Blocked Trial Expected Response motion BOLD response t t R. M. Birn, P. A. Bandettini, R. W. Cox, R. Shaker, Event - related fMRI of tasks involving brief motion. Human Brain Mapping 7: 106-114 (1999).

55. Speaking - ER-fMRI avg Expected Response R. M. Birn, P. A. Bandettini, R. W. Cox, R. Shaker, Event - related fMRI of tasks involving brief motion. Human Brain Mapping 7: 106-114 (1999).

57. R. M. Birn, R. W. Cox, P. A. Bandettini, Detection versus estimation in Event- Related fMRI: choosing the optimal stimulus timing. NeuroImage 15: 262-264, (2002).

58. Neuronal Activation Input Strategies 1.Block Design 2. Parametric Design 3. Frequency Encoding 4. Phase Encoding 5. Event Related 6. Orthogonal Design 7. Free Behavior Design

59. Free Behavior Design Use a continuous measure as a reference function: Task performance Skin Conductance Heart, respiration rate.. Eye position EEG

60. Amygdala Sympathetic Nervous System The Skin Conductance Response (SCR) Ventromedial PFC Hypothalamus Resistance change across two electrodes induced by changes in sweating. Sweat Gland Orbitofrontal Cortex

61. Brain activity correlated with SCR during “Rest” J. C. Patterson II, L. G. Ungerleider, and P. A Bandettini, Task - independent functional brain activity correlation with skin conductance changes: an fMRI study. NeuroImage (in press)

62. OHBM 2002

65. Shimming Acoustic Noise Multishot Techniques Increased Gradient Performance Higher Field Strengths Surface Coil Arrays Calibration / Quantification Embedded Functional Contrast Noise / Fluctuations Direct Neuronal Current Imaging Clinical Populations Neuronal,Vascular, and Metabolic Information

66. Director: Peter Bandettini Staff Scientists: Sean Marrett Jerzy Bodurka Frank Ye Wen-Ming Luh Computer Specialist: Adam Thomas Post Docs: Rasmus Birn Hauke Heekeren David Knight Patrick Bellgowan Ziad Saad FIM Unit & FMRI Core Facility Graduate Student: Natalia Petridou Post-Back. IRTA Students: Elisa Kapler August Tuan Dan Kelley Visiting Fellows: Sergio Casciaro Marta Maieron Guosheng Ding Clinical Fellow: James Patterson Psychologist: Julie Frost Summer Students: Hannah Chang Courtney Kemps Douglass Ruff Carla Wettig Kang-Xing Jin Program Assistant: Kay Kuhns Scanning Technologists: Karen Bove-Bettis Paula Rowser