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Basics of fMRI Preprocessing Douglas N. Greve greve@nmr.mgh.harvard.edu

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2 fMRI Analysis Overview Higher Level GLM First Level GLM Analysis First Level GLM Analysis Subject 3 First Level GLM Analysis Subject 4 First Level GLM Analysis Subject 1 Subject 2 CXCXCXCX Preprocessing MC, STC, B0 Smoothing Normalization Preprocessing MC, STC, B0 Smoothing Normalization Preprocessing MC, STC, B0 Smoothing Normalization Preprocessing MC, STC, B0 Smoothing Normalization Raw Data CX

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3 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

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4 Input 4D Volume 64x64x35 85x1

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5 Preprocessing Start with a 4D data set 1. Motion Correction 2. Slice-Timing Correction 3. B0 Distortion Correction 4. Spatial Normalization 5. Spatial Smoothing End with a 4D data set Can be done in other orders Not everything is always done Note absence of temporal filtering

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6 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

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7 Motion Sometimes effect on signal is positive, sometimes negative

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8 One Effect of Uncorrected Motion on fMRI Analysis Ring-around-the-brain From Huettel, Song, McCarthy

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9 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

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10 Motion Correction Motion correction reduces motion Not perfect RawCorrected

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11 Motion Correction Motion correction parameters Six for each time point Sometimes used as nuisance regressors How much motion is too much?

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12 Slice Timing Ascending Interleaved Volume not acquired all at one time Acquired slice-by-slice Each slice has a different delay

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Volume = 30 slices TR = 2 sec Time for each slice = 2/30 = 66.7 ms 0s 2s Effect of Slice Delay on Time Course

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14 Slice Timing Correction 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! X TR1TR2TR3 Slice

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15 Every other slice is bright Interleaved slice acquisition Happens with sequential, harder to see Motion, Slice Timing, Spin History

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16 Motion, Slice Timing, Spin History Slice 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 TR1TR2TR3

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17 B0 Distortion 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 Stretch Dropout

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B0 Map Echo 2 TE2 Magnitude Echo 1 TE1 Phase Voxel Shift Map

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19 Voxel Shift Map Units are voxels (3.5mm) Shift is in-plane Blue = P A, Red A P Regions affected near air/tissue boundaries sinuses

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20 B0 Distortion Correction Can only fix metric distortion Dropout is lost forever

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21 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

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22 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)

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23 Spatial Normalization Subject 1 Subject 2 Subject 1 Subject 2 MNI305 MNI152 Native SpaceMNI305 Space Affine (12 DOF) Registration

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24 Subject 1 Subject 2 aligned with Subject 1 (Subject 1’s Surface) Problems with Affine (12 DOF) Registration

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25 Surface Registration Subject 1Subject 2 (Before) Subject 2 (After)

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26 Surface Registration Subject 1Subject 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)

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27 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

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Spatial Smoothing Full-Width/Half-max Spatially convolve image with Gaussian kernel. Kernel sums to 1 Full-Width/Half-max: FWHM = /sqrt(log(256)) = standard deviation of the Gaussian 0 FWHM5 FWHM10 FWHM 2mm FWHM 10mm FWHM 5mm FWHM Full Max Half Max

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29 Spatial Smoothing

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Effect of Smoothing on Activation Working memory paradigm FWHM: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20

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31 Volume- vs Surface-based Smoothing 5 mm apart in 3D 25 mm apart on surface Averaging with other tissue types (WM, CSF) Averaging with other functional areas 14mm FWHM

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32 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

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33 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.

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34 fMRI Analysis Overview Higher Level GLM First Level GLM Analysis First Level GLM Analysis Subject 3 First Level GLM Analysis Subject 4 First Level GLM Analysis Subject 1 Subject 2 CXCXCXCX Preprocessing MC, STC, B0 Smoothing Normalization Preprocessing MC, STC, B0 Smoothing Normalization Preprocessing MC, STC, B0 Smoothing Normalization Preprocessing MC, STC, B0 Smoothing Normalization Raw Data CX

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35 Preprocessing Start with a 4D data set 1. Motion Correction - Interpolation 2. Slice-Timing Correction 3. B0 Distortion Correction - Interpolation 4. Spatial Normalization - Interpolation 5. Spatial Smoothing – Interpolation-like End with a 4D data set Can be done in other orders Note absence of temporal filtering

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