Jody Culham Brain and Mind Institute Department of Psychology University of Western Ontario http://www.fmri4newbies.com/ fMRI Data Quality Assurance and Preprocessing Last Update: January 28, 2013 Last Course: Psychology 9223, W2013, Western Data Quality The Black Box • The danger of automated processing and fancy images is that you can get blobs without every really looking at the real data • The more steps done at without quality assurance, the greater the chance of wonky results Raw Data Big Black Box of automated software Pretty pictures Your favorite fMRI software Slide adapted from Mark Daley Culham’s First Commandment: Know Thy Data • Look at raw functional images – Where are the artifacts and distortions? – How well do the functionals and anatomicals correspond? • Look at the movies – Is there any evidence of head motion? – Is there any evidence of scanner artifacts (e.g., spikes)? • Look at the time courses – Is there anything unexpected (e.g., abrupt signal changes at the start of the run)? – What do the time courses look like in the unactivatable areas (ventricles, white matter, outside head)? • Look at individual subjects • Double check effects of various transformations – Make sure left and right didn’t get reversed – Make sure functionals line up well with anatomicals following all transformations • Think as you go. Investigate suspicious patterns Sample Artifacts Ghosts Hardware Malfunctions Spikes Metallic Objects (e.g., hair tie) Contrast and Contrast:Noise T1 T2 High Contrast: Noise Low Contrast: Noise Why SNR Matters Note: This SNR level is not based on the formula given Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging Sources of Noise Physical noise • “Blame the magnet, the physicist, or the laws of physics” Physiological noise • “Blame the subject” How Can You Tell the Difference? • Test a phantom No physiological noise! A Map of Noise Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging • voxels with high variability shown in white Effect of Field Strength on Signal and Noise Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging • Although raw SNR goes up with field strength, so does thermal and physiological noise • Thus there are diminishing returns for increases in field strength Effect of Field Strength on Signal Effect of Field Strength on Vascular Signals Effect of Field Strength on Susceptibility 1.5 T 4.0 T Coils Head coil Surface coil • homogenous signal • moderate SNR • highest signal at hotspot • high SNR at hotspot Photo source: Joe Gati Phased Array Coils • SNR of surface coils with the coverage of head coils • OR… faster parallel imaging • modern scanners come standard with 8- or 12-channel head coils and capability for up to 32 channels 12-channel coil 32-channel coil 90-channel prototype Mass. General Hospital Wiggins & Wald 32-channel head coil Siemens Photo Source: Technology Review Phased Array Coils Source: Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging Voxel Size • Bigger is better… to a point • Increasing voxel size signals summate, noise cancels out • “Partial voluming”: If tissue is of different types, then increasing voxel size waters down differences – e.g., gray and white matter in an anatomical – e.g., activated and unactivated tissue in a functional Sampling Time • More samples More confidence effects are real What’s the most common source of physiological noise? Head Motion: Main Artifacts Head motion Problems 1) Rim artifacts • • hard to tell activation from artifacts artifacts can work against activation time1 time2 Playing a movie of slices over time helps you detect head motion Looking at the negative tail can help you identify artifacts 2) Region of interest moves •lose effects because you’re sampling outside ROI BV Correction During Single Run Head Motion: Good, Bad,… run 1 run 2 run 3 run 4 run 5 run 6 Slide from Duke course … and really, really ugly! Slide from Duke course Motion Correction Algorithms roll yaw y translation z translation pitch x translation • • • Most algorithms assume a rigid body (i.e., that brain doesn’t deform with movement) Align each volume of the brain to a target volume using six parameters: three translations and three rotations Target volume: the functional volume that is closest in time to the anatomical image BVQX Motion Correction Options Analysis/fMRI 2D data preprocessing menu Align each volume to the volume closest in time to the anatomical – Why? Mass Motion Artifacts • motion of any mass in the magnetic field, including the head, is a problem grasparatus gaze head coil brace arm brace Mass Motion Artifacts Grasping and reaching data from block designs circa 1998 Even in the absence of head motion, mass motion creates huge problems 1.0 .60 -.60 Where is the signal phantom correlated with the (fluid-filled masssphere) position? 30-1.0 s 30 s r value Motion Correction Parameters 7 900 Left Left Right Right Motion Detected (mm or degrees) % Signal Change Time Course: Left 0 -4 0 0 0 30 60 90 Time (seconds) 120 150 0.6 0 -0.4 0 30 60 90 120 150 Time (seconds) Culham, chapter in Cabeza & Kingstone, Handbook of Functional Neuroimaging of Cognition (2nd ed.), 2006 Mass Motion Distort Magnetic Field Barry et al., in press, Magnetic Resonance Imaging Motion Correction Algorithms • Existing algorithms correct two of our three problems: √ 1. Head motion leads to spurious activation √ 2. Regions of interest move over time X 3. Motion of head (or any other large mass) leads to changes to field map • Sometimes algorithms can introduce artifacts that weren’t there in the first place (Friere & Mangin, 2001, NeuroImage) The Fridge Rule • When it doubt, throw it out! Head Restraint Vacuum Pack Head Vise (more comfortable than it sounds!) Bite Bar Thermoplastic mask Often a whack of foam padding works as well as anything Prospective Motion Correction • Siemens Prospective Acquisition CorrEction (PACE) • shifts slices on-the-fly so that slice planes follow motion • Siemens claims it improves data quality • Caution: unlike retrospective motion correction algorithms, you can never get “raw” data Source: Siemens Prevention is the Best Remedy • Tell your subjects how to be good subjects – “Don’t move” is too vague • Make sure the subject is comfy going in – avoid “princess and the pea” phenomenon • Emphasize importance of not moving at all during beeping – – – – – do not change posture if possible, do not swallow do not change posture do not change mouth position do not tense up at start of scan • Discourage any movements that would displace the head between scans • Do not use compressible head support • For a summary of info to give first-time subjects, see http://defiant.ssc.uwo.ca/Jody_web/Subject_Info/firsttime_subjects.htm Mock “0 T” Scanners Data Preprocessing Recommended Newish Book Software And you thought people were opinionated about Mac vs. PC! Table from Poldrack, Mumford & Nichols, 2011 Functional Data Organization Image from Mark Daley fMRI data has 4 dimensions •3 Space: x (L-R), y (A-P), z (S-I) •1 Time •“Volume” = 3 spatial dimensions at one point in time Image from Poldrack et al., 2011 • Each value in our 4-dimensional matrix is image intensity (blackwhite) • The inherent scale may be arbitrary or normalized Sample Preprocessing Sequence Figure from Poldrack, Mumford & Nichols, 2011 Disdaqs • Discarded data acquisitions: trashed volumes at the beginning of a run before the magnet has reached a steady state • The scanner may throw out the disdaqs before it saves the data or it may save them too, in which case you have to discard them in your software • Sometimes it can take awhile for the subject to reach a steady state too -Startle response! T1, T2, T2* Image from Poldrack et al., 2011 • Different image types have different resolution, contrast polarity, and distortions • Nevertheless, we must ensure that the functional data (T2*) align well with the anatomical data (typically T1) • Use file headers to determine spatial alignment between data types, then tweak if needed Field Map Correction • Remember we collect data in frequency space not image space • Remember that our data collection assumes a homogeneous main magnetic field • If the magnetic field is not fully homogeneous, we get distortions in frequency space and image space • If we collect a “field map” we can correct these distortions http://www.mathworks.com/matlabcentral/fileexchange/30853-field-mapping-toolbox BV Preprocessing Options Slice Order NonInterleaved; Descending The first slice is collected almost a full TR (e.g., 2 s) before the last slice Problem with noninterleaved slices: excitation of one slice may carry over to next slice Slice Order Interleaved; Descending The first yellow slice is collected almost a full TR (e.g., 2 s) before the last pink slice Slice Scan Time Correction Slice Scan Time Correction • interpolates the data from each slice such that is is as if each slice had been acquired at the same time Source: Brain Voyager documentation BV Preprocessing Options Spatial Smoothing Gaussian kernel • smooth each voxel by a Gaussian or normal function, such that the nearest neighboring voxels have the strongest weighting Maximum Half-Maximum Full Width at Half-Maximum (FWHM) -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 FWHM = 6 3D Gaussian smoothing kernel Effects of Spatial Smoothing on Activity No smoothing 4 mm FWHM 7 mm FWHM 10 mm FWHM Should you spatially smooth? • Advantages – Increases Signal to Noise Ratio (SNR) • Matched Filter Theorem: Maximum increase in SNR by filter with same shape/size as signal – Reduces number of comparisons • Allows application of Gaussian Field Theory – May improve comparisons across subjects • Signal may be spread widely across cortex, due to intersubject variability • Disadvantages “Why would you spend $4 million to buy an MRI scanner and then blur the data till it looked like PET?” -- Ravi Menon – Reduces spatial resolution – Challenging to smooth accurately if size/shape of signal is not known Slide from Duke course BV Preprocessing Options Components of Time Course Data Source: Smith chapter in Functional MRI: An Introduction to Methods Linear Drift Huettel, Song & McCarthy, 2004, Functional Magnetic Resonance Imaging BV Preprocessing Options Before LTR: After LTR: BV Preprocessing Options High pass filter •pass the high frequencies, block the low frequencies •a linear trend is really just a very very low frequency so LTR may not be strictly necessary if HP filtering is performed (though it doesn’t hurt) Before High-pass linear drift ~1/2 cycle/time course ~2 cycles/time course After High-pass BV Preprocessing Options • Gaussian filtering – each time point gets averaged with adjacent time points – has the effect of being a low pass filter • passes the low frequencies, blocks the high frequencies – for reasons we will discuss later, I recommend AGAINST doing this Before Gaussian (Low Pass) filtering After Gaussian (Low Pass) filtering A Brief Primer on Fourier Analysis • Sine waves can be characterized by frequency and amplitude amplitude peak trough peak: high point trough: low point frequency: number of cycles within a certain time or space (e.g., cycles per sec = Hz, cycles per cm) amplitude: height of wave phase: starting point • (b) has same frequency as (a) but lower amplitude • (c) has lower frequency than (a) and (b) • (d) has same frequency and amplitude as (c) but different phase Source: DeValois & DeValois, Spatial Vision, 1990 Fourier Decomposition • Any wave form can be decomposed into a series of sine waves Frequency spectrum Source: DeValois & DeValois, Spatial Vision, 1990 Temporal and Spatial Analysis Temporal waveforms • e.g., sound waves • e.g., fMRI time courses Spatial waveforms • can be one dimensional (e.g., sine wave gratings in vision) or two dimensional (e.g., a 2D image) • e.g., image analysis • e.g., an fMRI slice (kspace) Source: DeValois & DeValois, Spatial Vision, 1990 Fourier Synthesis • centre = low frequencies • periphery = high frequencies • You can see how the image quality grows as we add more frequency information Source: DeValois & DeValois, Spatial Vision, 1990 “Low-Pass” vs. “High-Pass” Low-pass • pass the low frequencies through the filter • remove the high frequencies • you could also call this temporal smoothing High-pass • pass the low frequencies through the filter • remove the high frequencies Find the “Sweet Spots” • Even in a “resting state scan” (i.e., when subject isn’t doing a task), certain frequencies are present Respiration • every 4-10 sec (0.3 Hz) • moving chest distorts susceptibility Cardiac Cycle • every ~1 sec (0.9 Hz) • pulsing motion, blood changes Solutions • gating • avoiding paradigms at those frequencies You want your paradigm frequency to be in a “sweet spot” away from the noise Order of Preprocessing Steps is Important • Thought question: Why should you run motion correction before temporal preprocessing (e.g., linear trend removal)? • If you execute all the steps together, software like Brain Voyager will execute the steps in the appropriate order • Be careful if you decide to manually run the steps sequentially. Some steps should be done before others. SSTC and 3DMC Interact Take-Home Messages • Look at your data • Work with your physicist to minimize physical noise • Design your experiments to minimize physiological noise • Motion is the worst problem: When in doubt, throw it out • Preprocessing is not always a “one size fits all” exercise EXTRA SLIDES What affects SNR? Physical factors PHYSICAL FACTORS SOLUTION & TRADEOFF Thermal Noise (body & system) Inherent – can’t change Magnet Strength e.g. 1.5T 4T gives 2-4X increase in SNR Use higher field magnet Coil e.g., head surface coil gives ~2+X increase in SNR Use surface coil Voxel size e.g., doubling slice thickness increases SNR by root2 Use larger voxel size Sampling time Longer scan sessions – additional cost and maintenance – physiological noise may increase – Lose other brain areas – Lose homogeneity – Lose resolution – additional time, money and subject discomfort Source: Doug Noll’s online tutorial Head Motion: Main Artifacts 1. Head motion can lead to spurious activations or can hinder the ability to find real activations. • Severity of problem depends on correlation between motion and paradigm 2. Head motion increases residuals, making statistical effects weaker. 3. Regions move over time – ROI analysis: ROI may shift – Voxelwise analyses: averages activated and nonactivated voxels 4. Motion of the head (or any other large mass) leads to changes to field map 5. Spin history effects • Voxel may move between excitation pulse and readout Motion Intensity Changes A B C 507 89 154 663 507 89 119 171 83 520 119 171 179 117 53 137 179 117 Slide modified from Duke course Motion Spurious Activation at Edges lateral motion in x direction brain position stat map motion in z direction (e.g., padding sinks) time1 time2 time 1 > time 2 time 1 < time 2 Spurious Activation at Edges • spurious activation is a problem for head motion during a run but not for motion between runs Motion Increased Residuals × 1 = + + × 2 fMRI Signal “our data” = = Design Matrix x Betas “what we CAN explain” x “how much of it we CAN explain” + Residuals + “what we CANNOT explain” Statistical significance is basically a ratio of explained to unexplained variance Regions Shift Over Time time1 time2 • A time course from a selected region will sample a different part of the brain over time if the head shifts • For example, if we define a ROI in run 1 but the head moves between runs 1 and 2, our defined ROI is now sampling less of the area we wanted and more of adjacent space • This is a problem for motion between runs as well as within runs Problems with Motion Correction • lose information from top and bottom of image – possible solution: prospective motion correction • calculate motion prior to volume collection and change slice plan accordingly we’re missing data here we have extra data here Time 1 Time 2 Why Motion Correction Can Be Suboptimal 1. Parts of brain (top or bottom slices) may move out of scanned volume (with z-direction motion or rotations) 2. Motion correction requires spatial interpolation, leads to blurring – fast algorithms (trilinear interpolation) aren’t as good as slow ones (sinc interpolation) – Motion correction Why Motion Correction Algorithms Can Fail • Activation can be misinterpreted as motion – particularly problematic for least squares algorithms (Friere & Mangin, 2001) • Field distortions associated with moving mass (including mass of the head) can be misinterpreted as motion Spurious activation created Mutual information by motion correction in algorithm in SPM has SPM (least squares) fewer problems Simulated activation Friere & Mangin, 2001 Solution to Mass Motion Artifcact (e.g., speech, hand actions) Solution: • employ a slow event-related design with one trial every ~14 s • artifacts occur at the time of motion • BOLD response is delayed ~5 sec action artifact activity fMRI Signal 0 IMPORTANT: Subject must remain in constant configuration between trials 5 10 Time (Sec) Different motions; different effects Drift within run Movement between runs Uncorrelated abrupt movement within run Correlated abrupt movement within a run Motion correction Spurious activations okay, corrected by LTR okay minor problem huge problem can reduce problems Increased residuals okay, corrected by LTR okay problem problem can reduce problems; may be improved by including motion parameters as predictors of no interest Regions move problem minor-major problem depending on size of movement problem problem can reduce problems; if algorithm is fooled by physics artifacts, problem can be made worse by MC Physics artifacts not such a problem because effects are gradual okay problem huge problem can’t fix problem; may be misled by artifacts Effect of Temporal Filtering before after Source: Brain Voyager course slides Trial-to-trial variability Single trials Average of all trials from 2 runs Spatial Distortions Core Cross-section Before Correction A Lengthwise Cross-section Before Correction B Lengthwise Cross-Section After Correction C Isocentre Top Isocentre + 12 cm Bottom D E F Homogeneity Correction Data Preprocessing Options reconstruction from raw k-space data • frequency space real space artifact screening • ensure the data is free from scanner and subject artifacts vessel suppression • reduce the effects of large vessels (which are further away from activation than capillaries) slice scan time correction • correct for sampling of different slices at different times motion correction • correct for sampling of different slices at different times spatial filtering • smooth the spatial data temporal filtering • remove low frequency drifts (e.g., linear trends) • remove high frequency noise (not recommended because it increases temporal autocorrelation and artificially inflates statistics) spatial normalization • put data in standard space (Talairach or MNI Space) What affects SNR? Physiological factors PHYSIOLOGICAL FACTORS SOLUTION & TRADEOFF Head (and body) motion Use experienced or well-warned subjects – limits useable subjects Use head-restraint system – possible subject discomfort Post-processing correction – often incompletely effective – 2nd order effects – can introduce other artifacts Single trials to avoid body motion Cardiac and respiratory noise Monitor and compensate – hassle Low frequency noise Use smart design Perform post-processing filtering BOLD noise (neural and vascular fluctuations) Use many trials to average out variability Behavioral variations Use well-controlled paradigm Use many trials to average out variability Source: Doug Noll’s online tutorial Slice Scan Time Correction original time course shifted time course • Slice scan time correction adjusts the timing of a slice corrected at the end of the volume so that it is as if it had been collected simultaneously with the first slice Source: Brain Voyager documentation Calculating Signal:Noise Ratio Pick a region of interest (ROI) outside the brain free from artifacts (no ghosts, susceptibility artifacts). Find mean () and standard deviation (SD). Pick an ROI inside the brain in the area you care about. Find and SD. e.g., =4, SD=2.1 SNR = brain/ outside = 200/4 = 50 [Alternatively SNR = brain/ SDoutside = 200/2.1 = 95 (should be 1/1.91 of above because /SD ~ 1.91)] When citing SNR, state which denominator you used. Head coil should have SNR > 50:1 Surface coil should have SNR > 100:1 Source: Joe Gati, personal communication e.g., = 200 WARNING!: computation of SNR is complicated for phased array coils WARNING!: some software might recalibrate intensities so it’s best to do computations on raw data