Choosing the Optimal Sequences and Strategies for Functional MRI

1. Choosing the Optimal Sequences and Strategies for Functional MRI Peter A. Bandettini, Ph.D Unit on Functional Imaging Methods Laboratory of Brain and Cognition National Institute of Mental Health

2. Variables to Optimize • Information Content • Sensitivity • Speed • Resolution • Image quality

3. Variables to Optimize • Information Content • Sensitivity • Speed • Resolution • Image quality

4. Information Content • Blood Volume • Blood Oxygenation • Blood Perfusion • Hemodynamic Specificity • Mapping of CMRO2

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

6. Blood Volume

7. Susceptibility Contrast

8. Blood Oxygenation

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

12. Blood Perfusion EPISTAR FAIR . . . - - - - Perfusion Time Series . . .

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

14. Perfusion Rest Activation BOLD

15. Anatomy BOLD Perfusion

16. +- • unique information • baseline information • multislice trivial • invasive • low C / N for func. Volume BOLD Perfusion • highest C / N • easy to implement • multislice trivial • non invasive • highest temp. res. • complicated signal • no baseline info. • unique information • control over ves. size • baseline information • non invasive • multislice non trivial • lower temp. res. • low C / N

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

18. Mapping of CMRO2 Activation: Flow CMRO2 Blood Oxygenation CO2 stress: Flow CMRO2 Blood Oxygenation

19. 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) hypercapnia visual stimulation Hoge, et al. CMRO2-related BOLD signal deficit: CBF BOLD Simultaneous Perfusion and BOLD imaging during graded visual activation and hypercapnia N=12

20. 4 +10 +20 -10 0 25 3 20 15 CMRO2 (% increase) BOLD (% increase) 2 10 5 1 0 0 10 20 30 40 50 Perfusion (% increase) 0 0 10 20 30 40 50 Perfusion (% increase) Hoge, et al. CBF-CMRO2 coupling Characterizing Activation-induced CMRO2 changes using calibration with hypercapnia

21. Hoge, et al. Computed CMRO2 Changes 40 30 20 10 0 % % -10 -20 -30 -40 Subject 2 Subject 1

22. Variables to Optimize • Information Content • Sensitivity • Speed • Resolution • Image quality

23. Sensitivity • Optimizing fMRI Contrast • Maximizing Signal • Reducing Physiologic Fluctuations • Minimizing Temporal Artifacts

24. Optimizing fMRI Contrast • Increase field strength • Adjust pulse sequence timing (TE ≈ T2*) • Adjust voxel volume (≈ activation volume)

25. Asymmetric Spin - Echo Gradient - Echo

26. Asymmetric Spin - Echo Gradient - Echo

27. Asymmetric Spin - Echo Gradient - Echo

28. Maximizing Signal • Higher Bo Field • Radio frequency Coils • Choice of repetition time (TR) • Voxel volume

29. Physiologic Fluctuations Cardiac 0.6 to 1.2 Hz Respiratory 0.1 to 0.2 Hz Low Frequency 0.0 to 0.1 Hz

30. 0.25 Hz Breathing at 1.5T 3ms 3ms Image 26ms Power Spectra Respiration map 49ms 0 0.25 0.5 Hz

31. 0.68 Hz Cardiac rate at 3T 3ms Image 26ms Power Spectra Cardiac map 49ms 0 0.68 (aliased) 0.5 Hz

32. Temporal vs. Spatial SNR- 3T 26ms 49ms 26ms 49ms SPIRAL 27ms 50ms 27ms 50ms EPI

33. Reducing Physiologic Fluctuations • Filtering • Pulse sequence • single vs. multishot • strategies for multishot • Gating with correction for variable TR

34. Temporal Artifacts • System instabilities • Motion • Drift • Stimulus correlated • Stimulus uncorrelated

35. Minimizing Temporal Artifacts • Recognize? • Edge effects • Shorter signal change latencies • Unusually high signal changes • External measuring devices • Correct? • Image registration algorithms • Orthogonalize to motion-related function (cardiac, respiration, movement) • Navigator echo for k-space alignment (for multishot techniques) • Re-do scan • Bypass? • Paradigm timing strategies.. • Gating (with T1-correction) • Suppress? • Flatten image contrast • Physical restraint • Averaging, smoothing

38. Overt Word Production 2 3 4 5 6 7 8 9 10 11 12 13

39. Tongue Movement Jaw Clenching

40. Variables to Optimize • Information Content • Sensitivity • Speed • Resolution • Image quality

41. Speed • Rapid imaging techniques: • Single shot imaging • TR vs. Brain coverage: min TR = (time/slice) x number of slices in volume • Hemodynamic Issues • Paradigm timing • Event related fMRI • Timing modulation

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

45. 2 1000 msec 1.5 100 msec 34 msec 1 0.5 0 -0.5 -1 15 20 25 30 35 Time (sec)

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

48. 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

49. Results – visual task Nonlinearity Magnitude Latency

50. Results – motor task Nonlinearity Magnitude Latency