Pipelines for different techniques Flashcards
at a basic level, how is fMRI showing brain function
seeing which brain regions ‘light-up’ during a particular task e.g. visual cortex lights up during visual task
draw the flow chart from stimulus to BOLD response
see diagram
who first experimentally indicated relationship between blood flow and brain function?
Angelo Mossi (balance board 19th century)
overall fMRI set up
person lying in MRI magnet with RF head coil, headphones, mirror to see screen, holding response box for output
is the BOLD signal directly measuring blood flow?
no
if BOLD signal is not directly measuring blood flow, what is it measuring?
it is sensitive to the magnetic properties of oxygenated and deoxygenated RBCs
outline the oxygenated properties of RBCs
diamagnetic- slightly (indistinguishably) reduces magnetic field
outline deoxygenated properties of RBCs
paramagnetic- slightly increases magnetic field (distinguishable)
if magnetic field increases, precession…
increases
so if magnetic field increases where deoxygenated RBCs are present, what happens
it cause a magnetic field gradient causing adjacent water molecules to precess at different frequencies then dephase (spread out to x and y planes) causing signal loss - results in a distinguishable signal loss around deoxygenated blood, in comparison to oxygenated blood
outline activation contrast occurring in BOLD (comparing rest to activation)
at rest: oxygenated blood travels through arteries. exchanges oxygen in capillary bed and deoxygenated blood leaves via veins. Deoxygenated blood increases dephasing, hence increases T2 signal.
When active: excess oxygenated blood flows into activated region, washing out deoxygenated blood, this reduces dephasing, hence reduces T2 signal
The slight change in T2 signal between rest and activity can be expressed mathematically to give an optimum echo time
draw diagrams to represent the different techniques used for structural MRI data acquisition in K-space vs fMRI (echo planar)
see notes
why does fMRI use echo planar imaging
it’s much faster- can acquire a single slice in less than 100ms
what pattern does fMRI echo planar use
interleaved
what’s the disadvantage of interleaved echo planar
it can lead to stripes on the image due to the artefact of signal changes during acquisition or subject motion
in fMRI how is signal intensity time course looked at?
looked at along rest/task/rest/task etc. voxel by voxel- to see which voxels show difference in signal between rest and activation
what is the method of fMRI data analysis focussed on?
model based linear regression
outline the development of models to fit voxel signal activity- with images
we have our voxel signal activity going up and down between rest and task- see notes
a simple model is a poor fit for the data as the data is shifted in time due to delayed response to stimulus
improved model is time shifted to better fit this
then we take physiology into account- the sloped haemodynamic response with delay then decay
this is convoluted with the simple time shifted model
then due to signal drift over time is combined with linear ramp- best fit
outline how a study like the 10 year f/u on hippocampal volume using MRI in early dementia and cognitive decline would be run
MRI baseline of volume and repeat at defined intervals for each participant
hippocampal segmentation from a regulizer and probabilistic atlas- from registered brains
normalise volume overtime compared to see hippocampal volume changes and whether it aligns with dementia/cognitive decline
(overall- raw volume calculation -> normalisation -> percentage loss overtime calculated-)
what is the downside of ROI analysis?
you need to know what you want to look at (ROI)- an a-priori hypothesis
what do you do if you don’t have a ROI or an a-priori hypothesis
an exploratory study where you don’t have to work within pre-defined areas- this is usually Voxel Based Morphometry (VBM)
what is VBM?
a global volumetric brain analysis where a single experiment allows identification of GM changes and other associations across brain
does VBM use the same or different tools of image analysis as ROI studies?
the same
what are the steps/tools used in VBM image processing?
Brain extraction, GM tissue segmentation, templates, registration, smoothing, stats testing
outline Brain extraction (BET) in VBM
all images organised and assembled in the same directory, BET on FSL will make all pixels that aren’t brain =0
these outputs need to be checked to ensure there’s no major issues
how is GM tissue segmentation done in VBM
GM TPM is made and overlaid on the extracted brain of participant
TPM is quantitative so voxels have values conveying the fraction of voxel that contains GM (0-1)
discuss uneven group sizes in VBM
it’s ok to have uneven group sizes in statistical analysis, but how this effects the template image has to be considered as we want the template to be equally representative of all participants so average morphology isn’t biased towards one group and to prevent more noise being created in images of one group than the other has it needs to be altered more in registration to fit template.
This is prevented by cutting out randomly the excess scans in the larger group so N=N
Outline the steps of VBM templates and registrations
- overall, a VBM experiment requires all images to share same space, but registration induces noise, therefore we try to get template image from data we are using in analysis taking it more geometrically similar to scans
- firstly, all scans are listed on FSL VBM (ensuring balanced numbers)
- MNI152 scan used as starting point for template brain, initially a 12DOF linear registration to approximate MNI152, then non-linear registration. Then we apply this to their GM TPM (co registration)
- this gives us an average of all images in MNI152 space
- we then go back to our native space GM TPMs and perform new linear and non-linear registrations between these and this new GM template, instead to the MNI152 template- gives less noisy template
- now every GM TPM should have reasonably high quality transformation into shared space
after VBM registration, what can we do?
voxelwise analysis
what is voxelwise analysis?
running a stats test per every voxel in the brain
what does voxelwise analysis after the aforementioned registration process overlook?
the ability to detect GM atrophy by differentiating between high and low GM values as GM atrophy primarily presents as thinning of cortex but this is lost in individual measurements during registration
how do we process images to ensure we can do voxelwise analysis to see GM loss for indiviual participants
when we perform our registration, we save a deformation map (the jacobians of the transformation)- an image where voxel values represent how much the cortical thickness was expanded/contracted during registration, so we can multiply this by transformation to give cortical thickness accurately
what is the purpose of smoothing?
to boost the signal to noise ratio
signal definition
patterns in our GM values which will underpin a statistical relationship. This is a numerical change in a consistent direction across all relevant voxels
noise definition
caused by image transformations and scanner/sequence imperfection it is a random numerical change of voxel value on top of true numerical values
what is the mechanism of smoothing?
signal can be relied on to be consistent across a region of scan, by averaging voxels with their neighbouring voxel values, it preserves brain atrophy while smoothing random noise across data - need a balance with smoothing as small regions of atrophy will have their signal smoothed out if too much applied
FSL VMB smooths data by 3 different degrees measurement in sigma (2,3,4) holding relationship to full width at half maximum (FWHM)
after smoothing data by 3 degrees, FSL VBM will run pilot stats to see which has the strongest stats values
higher sigma value=
higher FWM= smoothing over greater distance
outline statistical testing/analysis done with VBM data once processed
voxelwise analysis will perform stats test separately for every voxel coordinate across all pts
end up with a final image in template space where each voxel value= p-value for chosen stats test
there will be some random significant voxels, however, if data is truly significant it will be seen in a cluster
con of ROI analysis
very restricted in regional scope (needs a good a-priori hypothesis)
pro of ROI analysis
higher measurement accuracy and therefore statistical sensitivity for regions examined
pro of global analysis (VBM)
considers the whole brain, therefore nothing is ‘missed’
cons of global analysis (VBM)
elaborate processing an transformation steps create noise in final data - for a given region, statistical power will not be as high as it would be in ROI study of same area
multiple comparisons still unideal even after cluster-based correction
what is the linear regression model?
where our model of is time shifted with voxel signal up with HRF convolved linear ramp model
what is HRF
haemodynamic response function
how do we work out how well our model fits the data?
the data is a series of discrete signal measurements taken every few seconds with residual noise calculated by looking at the gap between model and actual data points
what is the equation for the general linear model (GLM)?
y = x beta e
what do the aspects of y = x beta e stand for ?
y = voxel time series data
x= design matrix
beta= regression parameters
e = gaussian noise
t-statistic definition
the ratio of the departure of the estimated value of a parameter from its hypothesis value to its standard error
what gives activation map?
threshold t-statistics where t-statistic is beyond threshold it lights up to show activation in this area
is fMRI quantitative?
no (we cab’t get the subject to perform a task and measure activation in meaningful units) therefore fMRI relies on signal contrast generated between states (e.g. task vs rest)
task definition
a set of activities usually involving stimuli and responses
run definition
a continuous period of data acquisition that has the same acquisition parameters and task
event definition
an isolated occurrence of stimulus being presented or a response being made
epoch definition
a period of sustained neural activity
trial definition
stimulus presentation followed by a response- can be treated as an event if less than 2 seconds
ISI definition
inter-stimulus- interval
ITI definition
inter-trial-interval
SOA definition
stimulus onset asynchrony
outline block designs
- earliest fMRI design mirroring that used in PET
- closely spaced successive trials over a short interval of time
- utilises blocks of identical trial types to establish task-specific conditions
draw diagram of block design
see notes
draw the block design to GLM regressor
see notes
advantages of block design
- most efficient design for detecting BOLD signal amplitude differences between conditions
- fairly robust
- can acquire more trials in less time than other designs because you don’t have to worry about spacing out individual trials to get an estimate of an individual event
disadvantages of block design
- predictable stimuli (subjects may know what is coming and alter strategies accordingly)
- inflexible for more complex tasks
- doesn’t account for any transient responses at the end of the block
- it can be difficult to determine an appropriate baseline condition
outline slow event related (ER) design
consists of short stimuli separated by fairly long ISI to enable HRF enough time to fallback to baseline before next trial
how do you workout the ideal ISI length
8s + 2 x stimulus duration