1. Statistical Parametric Mapping Lecture 4a - Chapter 7 Spatial and temporal resolution of fMRI Textbook: Functional MRI an introduction to methods, Peter Jezzard, Paul Matthews, and Stephen Smith Many thanks to those that share their MRI slides online

2. Spatial and Temporal Resolution Issues Spatial Resolution –Spatial sampling and alaising –Partial volume averaging alters strength of response based on voxel size and size of responding region Temporal Resolution –Temporal sampling and averaging –Would like to sample electrical activity which happens earlier than BOLD –Order and timing of events would improve modeling capabilities

3. Spatial Resolution Issues Excitatory and Inhibitory neural activity are both energy consuming, but upstream inhibited neurons produce less neuronal activity. Need to cover all regions of brain involved in the tested brain tasks (whole brain preferred). –Activity could be weaker due to partial volume effects at smaller nodes in a system level activated brain network. –Need to improve task induced change and reduce partial volume averaging. Position errors due to veins, macroscopic susceptibility, etc.

4. Impact of Spatial Resolution Extent of BOLD response (rb) is related to the extent of neuro- vascular response (rv) and the imaging spatial resolution extent (rs). General relationship rb 2 = rv 2 + rs 2 BOLD signal is variable due to partial volume averaging When rv < rs (voxel larger than signal region) rb ~ rs Bold signal is reduced by partial volume averaging When rv > rs (voxel smaller than signal region) rb ~ rv BOLD signal minimally affected by rs Based on classical linear system where output(x,y,z) = input(x,y,z)  PSF(x,y,z) But?

5. fMRI response ratio drops off with stimulus duration Dilution of signal into larger extent seems to be dominant effect 1.6 2.0 2.4 2.8 3.2 3.6 048121620 Stimulus duration (s) fMRI response ratio Figure 7.3 from textbook. time BOLD response, % initial dip positive BOLD response post stimulus undershoot overshoot 1 2 3 0 stimulus Initial dip – localized response (low signal) Overshoot next in extent (high signal) Plateau has greatest extent (high signal) Response extent Figure 8.1. from textbook.

6. Two Main Focus Points Responding well to changing hemodynamics –Initial dip in BOLD response more spatially specific to activated brain area than later rise in response, but later phase response is larger and needed for fMRI. –Hyperoxic response more broadly distributed spatially. Techniques to eliminate unwanted contributions to signal (increase CNR). –Short duration stimuli seem to be more narrowly distributed spatially than long duration stimuli in BOLD studies. –Higher B 0 appears to improve microvascular signals more than interfering signals –Better RF coils improve SNR –Improved motion correction improves CNR –Multi-shot EPI to reduce T2* blurring supports smaller voxels

7. Statistical Parametric Mapping Lecture 4b - Chapter 6 Selection of the optimal pulse sequence for fMRI Textbook: Functional MRI an introduction to methods, Peter Jezzard, Paul Matthews, and Stephen Smith Many thanks to those that share their MRI slides online

8. AdvantagesDisadvantages BOLDHighest activation contrast 2x-4x over perfusion (SPMs less noisy) complicated non-quantitative signal easiest to implementno baseline information multislice trivialsusceptibility artifacts can use very short TR Perfusionunique and quantitative informationlow activation contrast (need more temporal averaging) baseline informationlonger TR required easy control over observed vasculaturemultislice is difficult non-invasiveslow mapping of baseline information no susceptibility artifacts Table 6.1a. Summary of practical advantages and disadvantages of pulse sequences (derived from textbook)

9. AdvantagesDisadvantages Volumeunique informationinvasive baseline informationsusceptibility artifacts multislice trivialrequires separate run for each task rapid mapping of baseline information CMRO 2 unique and quantitative informationsemi-invasive extremely low activation contrast susceptibility artifacts processing intensive multislice is difficult longer TR required Table 6.1b. Continued summary of practical advantages and disadvantages of pulse sequences (derived from textbook)

10. Venous outflow Perfusion No Velocity Nulling Velocity Nulling ASL TI Time/secs12403 Venous outflow Figure 6.1a Signal is detected from water spins in the arterial-capillary region of the vasculature and from water in tissues surrounding the capillaries. Relative sensitivity controlled by adjusting TI and by incorporating velocity nulling gradients (also known as diffusion weighting). Nulling and TI~1 sec makes ASL sensitive to capillaries and surrounds. ArteriesArteriolesCapillariesVenulesVeins

11. GE-BOLD No Velocity Nulling Velocity Nulling Figure 6.1b Gradient Echo BOLD is sensitive to susceptibility perturbers of all sizes, and is therefore sensitive to all intravasculature and extravascular effects in the capillary-venous portions of the vasculature. If a very short TR is used may show signal from arterial inflow, which can be removed by using a longer TR and/or outer volume saturation. ArteriesArteriolesCapillariesVenulesVeins Arterial inflow (BOLD TR < 500 ms) Time/secs12403

12. SE-BOLD No Velocity Nulling Velocity Nulling Figure 6.1c Spin Echo BOLD is sensitive to susceptibility perturbers about the size of a red blood cell or capillary, making it predominantly sensitive to intravascular water spins in vessels of all sizes and to extravascular (tissue) water surrounding capillaries. Velocity nulling reduces the signals from larger vessesl. ArteriesArteriolesCapillariesVenulesVeins Arterial inflow (BOLD TR < 500 ms) Time/secs12403

13. Maximizing Signal Field Strength and sequence parameters –Higher B means higher SNR but more susceptibility issues –TE ~ T2* (30-40 msec @ 3T) for best activation contrast –TR large enough to cover volume of interest, sampling time consistent with experiment, >500 msec recommended, T1 increases with increasing B RF coils –Larger coil for transmit –Smaller coil for receive –RF inhomogeneity increases with B Voxel size –Match to volume of smallest desired functional area –1.5x1.5x1.5 suggested as optimal (Hyde et al., 2000) –T2* increase and activation signal increase with small voxels if shim is poor

14. Maximizing Signal Reducing physiological fluctuations –Cardiac and breathing artifacts (sampling issues) –Filtering to remove artifactual frequencies from time signal, breathing easier to manage by filtering –Pulse sequence strategies Snap shot (EPI) each image in 30-40 msec reduces impact of artifacts Multi-shot ghosting (spiral imaging, navigator pulses, retrospective correction) –Gating Acquiring image at consistent phase of cardiac cycle or respiration Problems (changing heart rate, wasted time)

15. Minimizing Temporal Artifacts Brain activation paradigm timing –On-off cycles usually > 8 seconds –Maximum number of cycles and maximum contrast between –Cycling activations no longer than 3-4 minutes Post processing –Motion correction Real time fMRI –Monitoring immediately and repeat if artifacts are excessive –Tuning of slice location

16. Minimizing Temporal Artifacts Physical restraint –Limited success –Cooperative subject helps Pulse sequence strategies –Clustered acquisition (auditory stimulation 4-6 seconds before acquisition) –Set phase encode direction to minimize overlap with brain areas of interest –Select image plane with most motion to minimize between plane motion artifacts –Crusher gradients to minimize inflow artifacts

17. Statistical Parametric Mapping Lecture 4c - Chapter 4 More fMRI Textbook: Functional MRI an introduction to methods, Peter Jezzard, Paul Matthews, and Stephen Smith Many thanks to those that share their MRI slides online

18. Effects of Field Homogeneity R2* = R2 + R2 mi +R2 ma R2 = transverse relaxation rate due to spin-spin interactions and diffusion through microscopic gradients R2 mi = transverse relaxation rate due to microscopic changes, i.e. deoxyhemoglobin R2 ma = transverse relaxation rate due to macroscopic field inhomogeneity R2* a is relaxation rate during activation R2* r is relaxation rate at rest Note: macroscopic components subtract off

19. Approximate GM Relaxation And Activation Induced Rexalation Rate Changes 1.5T3T T2100 ms80 ms T2*60 ms50 ms T2’150 ms133.3 ms  R2 =  (1/T2) -0.2 s -1 -0.4 s -1  R2* =  (1/T2*) -0.8 s -1 -1.6 s -1  R2’ =  (1/T2’) -0.6 s -1 -1.2 s -1 T2, T2* and T2’ (from ASE) of GM decrease with increasing field strength During activation relaxation rates decrease (T2 increase) slightly Activation induced changes in relaxation rates (  R2s) indicate potential for signal production

20. Fig. 4.1 BOLD response as a function of TE for different values of T2* r. Note that TE opt ~ T2* and that BOLD response increases with increasing T2* r. 0.025 0.020 0.015 0.010 0.005 0.000 050100150 TE, ms Signal, arb T2* r =80ms 70ms 60ms 50ms 40ms 30ms 20ms 10ms TE opt = optimal TE for BOLD contrast lies between T2* a and T2* r T2* a = 1/R2* a T2* r = 1/R2* r Echo Time Optimization Subscripts a and r indicate during activation and rest.

21. Fig. 4.2 Change in histogram of T2* for thick slab through brain with changing slice thickness. Note broadening of distribution with increasing thickness with shift away from T2* a toward shorter T2* r. 050100150 T2*, ms 4000 3000 2000 1000 0 number of voxels 1.9mm 3.8mm 5.9mm Effects of Field Homogeneity

22. Fig. 4.3 EPI obtained with TE= 60 and TR=3000 msec and 63 and 95 ky lines. Note recovery of signal loss in d vs c and ghosting in c. Spin Echo 4x4x4 mm 3 Gradient Echo EPI 2x2x2 mm 3

23. Fig. 4.4 Phase fluctuations at center of k-space over 42 seconds. Spikes are due to cardiac cycles and slower periodic signal due to respiratory cycles. 050010001500 navigator index 0.1 0.0 -0.1 -0.2 -0.3 navigator phase, degrees 0.2 Intra-scan Motion Signal Why would phase advance and retard?

24. Statistical Parametric Mapping Lecture 4d The big Picture of Brain Many thanks to those that share their MRI slides online

25. Brain Lobes + Occipital Lobe Cerebellum Temporal Lobe Frontal Lobe Brainstem Cerebrum Lobes Frontal Parietal Temporal Occipital

26. Brodmann’s Functional Map

27. Mango and Anatomy Talairach Daemon (TD) –Anatomical/functional labels –5 hierarchical levels Hemispheres Lobes Gyri Tissue Cellular Spatial Normalization –Supports x-y-z coordinate lookup of anatomical/functional labels using the TD