Basics of fMRI Preprocessing Douglas N. Greve greve@nmr.mgh.harvard.edu fMRI Analysis Overview Subject 1 Raw Data Preprocessing MC, STC, B0 Smoothing Normalization First Level GLM Analysis X Subject 2 Raw Data Preprocessing MC, STC, B0 Smoothing Normalization C First Level GLM Analysis X C Higher Level GLM Subject 3 Raw Data Preprocessing MC, STC, B0 Smoothing Normalization First Level GLM Analysis X X C C Subject 4 Preprocessing MC, STC, B0 Smoothing Normalization Raw Data First Level GLM Analysis X C 2 Preprocessing • Assures that assumptions of the analysis are met • Time course comes from a single location • Uniformly spaced in time • Spatial “smoothness” • Analysis – separating signal from noise 3 Input 4D Volume 64x64x35 85x1 4 Preprocessing • 1. 2. 3. 4. 5. • Start with a 4D data set Motion Correction Slice-Timing Correction B0 Distortion Correction Spatial Normalization Spatial Smoothing End with a 4D data set • • • Can be done in other orders Not everything is always done Note absence of temporal filtering 5 Motion • Analysis assumes that time course represents a value from a single location • Subjects move • Shifts can cause noise, uncertainty • Edge of the brain and tissue boundaries 6 Motion • Sometimes effect on signal is positive, sometimes negative 7 One Effect of Uncorrected Motion on fMRI Analysis • Ring-around-the-brain From Huettel, Song, McCarthy 8 Motion Correction Template Target Reference Input Time Point Difference (Error) • Adjust translation and rotation of input time point to reduce absolute difference. • Requires spatial interpolation 9 Motion Correction Raw Corrected •Motion correction reduces motion •Not perfect 10 Motion Correction • Motion correction parameters • Six for each time point • Sometimes used as nuisance regressors • How much motion is too much? 11 Slice Timing Ascending Interleaved • Volume not acquired all at one time • Acquired slice-by-slice • Each slice has a different delay 12 Effect of Slice Delay on Time Course • Volume = 30 slices • TR = 2 sec • Time for each slice = 2/30 = 66.7 ms 2s 0s Slice Slice Timing Correction TR1 TR2 TR3 X • Temporal interpolation of adjacent time points • Usually sinc interpolation • Each slice gets a different interpolation • Some slices might not have any interpolation • Can also be done in the GLM • You must know the slice order! 14 Motion, Slice Timing, Spin History • Every other slice is bright • Interleaved slice acquisition • Happens with sequential, harder to see 15 Slice Motion, Slice Timing, Spin History TR1 TR2 TR3 • In TR3 subject moved head up • Red is now the first slice • Pink is now not in the FoV • Red has not seen an RF pulse before (TR=infinite) and so will be very bright • Other slices have to wait longer to see an RF pulse, ie, the TR increases slightly, causes brightening. • Direction of intensity change depends on a lot of things 16 B0 Distortion Stretch Dropout • Metric (stretching or compressing) • Intensity Dropout • A result of a long readout needed to get an entire slice in a single shot. • Caused by B0 Inhomogeneity 17 B0 Map Magnitude Phase Voxel Shift Map Echo 1 TE1 Echo 2 TE2 Voxel Shift Map • Units are voxels (3.5mm) • Shift is in-plane • Blue = PA, Red AP • Regions affected near air/tissue boundaries • sinuses 19 B0 Distortion Correction • Can only fix metric distortion • Dropout is lost forever 20 B0 Distortion Correction • Can only fix metric distortion • Dropout is lost forever • Interpolation • Need: • “Echo spacing” – readout time • Phase encode direction • More important for surface than for volume • Important when combining from different scanners 21 Spatial Normalization • Transform volume into another volume • Re-slicing, re-gridding • New volume is an “atlas” space • Align brains of different subjects so that a given voxel represents the “same” location. • Similar to motion correction • Preparation for comparing across subjects • Volume-based • Surface-based • Combined Volume-surface-based (CVS) 22 Spatial Normalization Native Space MNI305 Space Subject 1 Subject 1 MNI305 MNI152 Subject 2 Subject 2 Affine (12 DOF) Registration 23 Problems with Affine (12 DOF) Registration Subject 1 Subject 2 aligned with Subject 1 (Subject 1’s Surface) 24 Surface Registration Subject 1 Subject 2 (Before) Subject 2 (After) 25 Surface Registration Subject 1 Subject 2 (Before) Subject 2 (After) • Shift, Rotate, Stretch • High dimensional (~500k) • Preserve metric properties • Take variance into account • Common space for group analysis (like Talairach) 26 Spatial Smoothing • Replace voxel value with a weighted average of nearby voxels (spatial convolution) • Weighting is usually Gaussian • 3D (volume) • 2D (surface) • Do after all interpolation, before computing a standard deviation • Similarity to interpolation • Improve SNR • Improve Intersubject registration • Can have a dramatic effect on your results 27 Spatial Smoothing • Spatially convolve image with Gaussian kernel. • Kernel sums to 1 • Full-Width/Half-max: FWHM = s/sqrt(log(256)) s = standard deviation of the Gaussian 0 FWHM 5 FWHM 10 FWHM Full-Width/Half-max Full Max 2mm FWHM Half Max 5mm FWHM 10mm FWHM Spatial Smoothing 29 Effect of Smoothing on Activation • Working memory paradigm • FWHM: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 Volume- vs Surface-based Smoothing 14mm FWHM • 5 mm apart in 3D • 25 mm apart on surface • Averaging with other tissue types (WM, CSF) • Averaging with other functional areas 31 Choosing the FWHM • No hard and fast rules • Matched filter theorem – set equal to activation size • How big is that? • Changes with brain location • Changes with contrast • May change with subject, population, etc • Two voxels – to meet the assumptions of Gaussian Random Fields (GRF) for correction of multiple comparisons 32 Temporal filtering • Replace value at a given time point with a weighted average of its neighbors • Should/Is NOT be done as a preprocessing step – contrary to what many people think. • Belongs in analysis. 33 fMRI Analysis Overview Subject 1 Raw Data Preprocessing MC, STC, B0 Smoothing Normalization First Level GLM Analysis X Subject 2 Raw Data Preprocessing MC, STC, B0 Smoothing Normalization C First Level GLM Analysis X C Higher Level GLM Subject 3 Raw Data Preprocessing MC, STC, B0 Smoothing Normalization First Level GLM Analysis X X C C Subject 4 Preprocessing MC, STC, B0 Smoothing Normalization Raw Data First Level GLM Analysis X C 34 Preprocessing • 1. 2. 3. 4. 5. • Start with a 4D data set Motion Correction - Interpolation Slice-Timing Correction B0 Distortion Correction - Interpolation Spatial Normalization - Interpolation Spatial Smoothing – Interpolation-like End with a 4D data set • • Can be done in other orders Note absence of temporal filtering 35 36