Latest Developments in fMRI

1. Latest Developments in fMRI bandettini@nih.gov 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. Engineering Computer Science Physics Statistics Cognitive Science Physiology Medicine Technology Methodology Neuroscience Interpretation Applications

3. Diff. tensor Technology Mg+ 7T >8 channels 1.5T,3T, 4T EPI on Clin. Syst. Venography Real time fMRI EPI SENSE Nav. pulses “vaso” Local Human Head Gradient Coils Quant. ASL Z-shim Baseline Susceptibility MRI Dynamic IV volume Spiral EPI ASL Current Imaging? BOLD Simultaneous ASL and BOLD Multi-shot fMRI Correlation Analysis CO2 Calibration Methodology Motion Correction Latency and Width Mod Parametric Design Multi-Modal Mapping Surface Mapping Baseline Volume Free-behavior Designs ICA Phase Mapping Mental Chronometry Multi-variate Mapping Linear Regression IVIM Deconvolution Fuzzy Clustering Event-related BOLD models PET correlation Interpretation IV vs EV ASL vs. BOLD Layer spec. latency Bo dep. Pre-undershoot PSF of BOLD TE dep Resolution Dep. Excite and Inhibit Extended Stim. Blood T2 Post-undershoot Metab. Correlation Linearity SE vs. GE CO2 effect Optical Im. Correlation Hemoglobin Fluctuations NIRS Correlation Balloon Model Electrophys. correlation Inflow Veins Complex motor Applications Memory Imagery Emotion Language Children Drug effects Motor learning Tumor vasc. Mirror neurons BOLD -V1, M1, A1 Presurgical Ocular Dominance Attention Volume - Stroke Clinical Populations V1, V2..mapping Priming/Learning D Volume-V1 Performance prediction Plasticity Face recognition 36 82 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03

4. BOLD Contrast task task • K. K. Kwong, et al, (1992) “Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.” Proc. Natl. Acad. Sci. USA. 89, 5675-5679. • S. Ogawa, et al., (1992) “Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc. Natl. Acad. Sci. USA.” 89, 5951-5955. • P. A. Bandettini, et al., (1992) “Time course EPI of human brain function during task activation.” Magn. Reson. Med 25, 390-397. • 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.

5. The Problem Measured Signal Neuronal Activation ? ? ? ? Hemodynamics Noise

6. Latest Developments… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

7. Latest Developments… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

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

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

10. First Event-related fMRI Results 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.

11. The major obstacle in BOLD contrast temporal resolution: + 2 sec Latency - 2 sec Magnitude Venogram P. A. Bandettini, The temporal resolution of Functional MRI in "Functional MRI" (C. Moonen, and P. Bandettini., Eds.), p. 205-220, Springer - Verlag,. 1999.

12. A tangent into venograms (3 Tesla)

13. MP-RAGE 3D T-O-F MRA 3D Venous PC MR Venogram

14. Hemi-Field Experiment 9.0 seconds 15 seconds 500 msec 500 msec 20 30 10 Time (seconds) Right Hemisphere Left Hemisphere

15. 0 10 20 30 500 ms 500 ms RightHemifield Left Hemifield + 2.5 s - = 0 s - 2.5 s

16. Cognitive Neuroscience Application: PNAS

17. A A A B B B Word vs. Non-word 0o, 60o, 120o Rotation Regions of Interest Inferior Frontal Gyrus Precentral Gyrus Middle Temporal Gyrus

18. No calibration Formisano, E. and R. Goebel, Tracking cognitive processes with functional MRI mental chronometry. Current Opinion in Neurobiology, 2003. 13: p. 174-181.

19. 11026–11031 PNAS September 26, 2000vol. 97 no. 20

20. Latest Developments… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

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

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

23. Partial k-space imaging 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.

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

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

26. SENSE Imaging ≈ 5 to 30 ms Pruessmann, et al.

27. Perfusion Rest Activation BOLD 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.

28. 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.

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

30. Menon, et al 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).

31. Latest Developments… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

32. NeuroImage,19: 132-144, (2003).

33. 8 Channel Array Quadrature Head Coil SNR 128 x 96 64 x 48 TSNR 128 x 96

34. 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

36. Latest Developments… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

37. 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.

38. time (s) Dynamic Nonlinearity Assessment 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 R. M. Birn, Z. Saad, P. A. Bandettini, (2001) “Spatial heterogeneity of the nonlinear dynamics in the fMRI BOLD response.” NeuroImage, 14: 817-826.

39. 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 Spatial Heterogeneity of BOLD Nonlinearity R. M. Birn, Z. Saad, P. A. Bandettini, (2001) “Spatial heterogeneity of the nonlinear dynamics in the fMRI BOLD response.” NeuroImage, 14: 817-826.

40. Sources of this Nonlinearity • Neuronal • Hemodynamic • Oxygen extraction • Blood volume dynamics Oxygen Extraction Flow In Flow Out D Volume

41. 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.

42. HBM 2003 Poster number: 308 The Negative BOLD Response in Monkey V1 Is Associated with Decreases in Neuronal Activity Amir Shmuel*†, Mark Augath, Axel Oeltermann, Jon Pauls, Yusuke Murayama, Nikos K. Logothetis

43. Evidence that inhibitory input produces increased blood flow

44. Number of spikes CBF Time / s 0 50 100 150 Time / s Divergence of spike rate and blood flow during parallel fiber stimulation Mathiesen, Caesar, Akgören, Lauritzen (1998), J Physiol 512.2:555-566

46. 40 30 20 10 0 % -10 -20 -30 -40 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) CBF BOLD Simultaneous Perfusion and BOLD imaging during graded visual activation and hypercapnia

47. Altered neurovascular coupling: Pathology, drugs Courtesy of Arno Villringer

48. Latest Developments… • Temporal Resolution • Spatial Resolution • Sensitivity and Noise • Information Content • Implementation

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