Peter A. Bandettini Unit on Functional Imaging Methods Laboratory of Brain and Cognition &

1. How Much Information Can We Extract from the fMRI Time Series? Peter A. Bandettini Unit on Functional Imaging Methods Laboratory of Brain and Cognition & Functional MRI Core Facility

3. Engineering Computer Science Physics Statistics Cognitive Science Physiology Medicine Technology Methodology Neuroscience Interpretation Applications

4. 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

5. Blood Volume Imaging Susceptibility Contrast agent bolus injection and time series collection of T2* or T2 - weighted images

6. Blood Oxygenation Imaging 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.

7. Blood Perfusion Imaging EPISTAR FAIR . . . - - - - Perfusion Time Series . . .

8. Williams, D. S., Detre, J. A., Leigh, J. S. & Koretsky, A. S. (1992) “Magnetic resonance imaging of perfusion using spin-inversion of arterial water.” Proc. Natl. Acad. Sci. USA 89, 212-216. Edelman, R., Siewert, B. & Darby, D. (1994) “Qualitative mapping of cerebral blood flow and functional localization with echo planar MR imaging ans signal targeting with alternating radiofrequency (EPISTAR).” Radiology 192, 1-8. Kim, S.-G. (1995) “Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping.” Magn. Reson. Med. 34, 293-301. Kwong, K. K. et al. (1995) “MR perfusion studies with T1-weighted echo planar imaging.”Magn. Reson. Med. 34, 878-887.

9. Simultaneous BOLD and Perfusion BOLD Perfusion

10. 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

11. MAGNET RESON MED 50 (2): 263-274 AUG 2003

12. Where fMRI can improve: • Sensitivity • Spatial Resolution • Temporal Resolution • Interpretation • Experimental • Design/Execution/Analysis • Other contrast mechanisms

13. Why Sensitivity? • More activated signal is present • Information in the fluctuations • Shorter scan times • More subtle comparisons • Buys higher resolution

14. NeuroImage

16. Increasing Sensitivity • Higher field strength • More and Smaller RF coils • Reduction of physiological noise

17. 8 Channel Array Quadrature Head Coil SNR 128 x 96 64 x 48 TSNR 128 x 96

18. 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

20. Why Higher Spatial Resolution? • Delineation of function • Possible gain in contrast to noise • Reduction of signal dropout • Better registration with high res anatomy

21. Ocular Dominance Column Mapping using fMRI calcarine Menon, R. S., S. Ogawa, et al. (1997). “Ocular dominance in human V1 demonstrated by functional magnetic resonance imaging.” J Neurophysiol 77(5): 2780-7. Optical Imaging R. D. Frostig et. al, PNAS 87: 6082-6086, (1990).

22. NEUROIMAGE 19 (2): 261-270 Part 1 JUN 2003

23. Increasing Spatial Resolution • Multi-shot Imaging (with navigators) • Partial k-space • Parallel imaging (SENSE, SMASH, etc..)

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

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

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

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

28. Why higher temporal resolution? • More slices per volume • Better delineation of hemodynamic response • Potentially better delineation neuronal activity timing

29. Increasing temporal resolution • Asynchronous task and TR timing • Reduce readout window width • Increased averaging • Focus on modulation of task timing • Calibration?

30. + 2 sec Latency - 2 sec Magnitude

31. Measured Signal Neuronal Activation ? ? ? Hemodynamics Noise

32. 9.0 seconds 15 seconds 500 msec 500 msec 20 30 10 Time (seconds) Hemi-Field Experiment Left Hemisphere Right Hemisphere

33. 500 ms 500 ms RightHemifield Left Hemifield + 2.5 s - = 0 s - 2.5 s

34. sdelay = 107ms 1 run: 1% Noise 4% BOLD 256 time pts /run 1 second TR Number t -1000 -500 0 500 1000 delay estimate (ms) 500 400 16 sec on/off Smallest latency Variation Detectable (ms) (p < 0.001) 300 8 sec on/off 200 100 0 0 5 10 15 20 25 30 11 Number of runs

35. Optimal Detection of Hemodynamic Latency

36. Cognitive Neuroscience Application: PNAS

37. 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

38. w 1 a Amp. d 0 0 0 5 10 15 0 5 10 15 Estimation of Delay, Width & Amplitude Conv. time (s) Adjust d, w, a to improve fit (Nelder-Mead simplex method) 20 0 0 5 10 15

39. p < 10 -6 p < 10 -5 p < 10 -4 p < 10 -3 p < 10 -2 Time Difference In msec > 300 250 to 300 200 to 250 150 to 200 100 to 150 Lexical effect Rotational effect Magnitude Delay Width Words > Nonwords Nonwords > Words 0 deg > 120 deg 120 deg > 0 deg

40. Interpretation • More direct neuronal information • More quantitative physiologic information

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

42. measured linear BOLD Response Signal Stimulus timing 0.25 s 0.5 s 1 s 2 s 20 s time (s) NeuroImage

44. Hemodynamic Comparisons Nonlinearity Magnitude Latency

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

46. 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.

47. Ongoing work: Modulation of neuronal activation • Planned work: • Single unit monkey recordings with identical stimuli • Identical experiments with MEG in humans

48. Experimental Design, Execution, and Analysis

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

50. SD = 4000 s. SD = 1000 ms. SD = 250 ms. Detectability – constant ISI SD – stimulus duration ISI – inter-stimulus interval Detectability 0 5 10 15 20 25 30 35 40 Average ISI (s)