Diffusion

Question 1

What is diffusion?

Answer 1

Diffusion is the random Brownian motion of molecules due to thermal processes.

Molecules aren’t sitting static, if they have thermal energy, so above 0 kelvin they will be moving around, we have found they randomly move around and this is the process we mean by diffusion

Depending on the type of liquid they move around at different rates

Question 2

What is diffusion imaging?

Answer 2

Diffusion imaging is an MRI technique that measures this mobility of molecules

Diffusion-weighted imaging (DWI) is based on measuring the random Brownian motion of water molecules within a voxel of tissue.

Generally, highly cellular tissues or those with cellular swelling exhibit lower diffusion coefficients

Question 3

What is the fundamental idea of how DWI works?

Answer 3

DWI is the attenuation(reduction) of T2* signal based on how easily water molecules are able to diffuse in that region

The more easily water can diffuse (i.e. the further a water molecule can move around during the sequence) the less initial T2* signal will remain

Question 4

How is a diffusion-weighted imaged generated with MRI?

Answer 4

A spin echo MRI sequence is sensitised to diffusion by adding two large diffusion weighting gradients around the 180 degree pulse.

The signal attenuation depends on the diffusion coefficient (D) and the diffusion weighting b-value, which is a function of the gradient magnitude and timing

Question 5

In white matter how much is signal attenuated?

Answer 5

signal is attenuated by around 60%

less signal attenuation, brighter

Question 6

In CSF how much is signal attenuated?

Answer 6

signal is attenuated by around 95%

High diffusion, very mobile molecules, lots of signal attenuation, very dark

Question 7

What is the difference between watery tissues and static/solid tissues in signal?

Answer 7

Watery tissue = mobile molecules = low signal intensity

Solid tissues = less mobile molecules = higher signal intensity

Question 8

How is diffusion measured?

Answer 8

Diffusion is measured along the gradient direction, which can be applied in any direction [x, y, z] by varying the amplitude of the x, y and z gradients.

Question 9

How does signal attenuation vary in humans?

Answer 9

In many human tissues, the amount of signal attenuation due to diffusion varies depending on the direction of the applied diffusion gradient [x, y, z]

Question 10

What are quantitative diffusion images?

Answer 10

As we also acquire a baseline image (S0) with no diffusion gradients, we can calculate the diffusion coefficient (D) in each direction.

These are quantitative diffusion images, where each voxel represents a diffusion value in in mm^2S^-1 and the different images represent diffusion measurements in different directions.

We can average the maps across all of the directions to produce a map of the mean diffusivity <D>.</D>

Question 11

What happens in human tissue that restricts diffusion?

Answer 11

Water is not free to move in human tissue, we have a complex microstructural environment and so diffusion is restrictred this e.g. by cell membranes

Question 12

What is a diffusion tensor?

Answer 12

In human tissue, diffusion is restricted by the complex microstructural environment

To characterise this environment, the diffusion process must be measured in many directions and is often described mathematically by a diffusion tensor

The diffusion tensor defines an ellipsoid in each voxel that characterises the diffusion properties.

Question 13

What is diffusion tensor imaging?

Answer 13

An advanced MRI technique that provides detailed information about tissue microstructure such as fiber orientation, axonal density, and degree of myelination

Its based on the measurement of the diffusion of water molecules.

Question 14

What are scalar diffusion images?

Answer 14

We can calculate different scalar images to provide a visual summary of the diffusion properties

Question 15

How do we generate scalar diffusion images?

Answer 15

The diffusion coefficient <D> is calculated from the T2 and DWI images and is directionally averaged</D>

If diffusion is calculated in multiple directions, a measure of the directional diffusion variability or “anisotropy” can be calculated.

Question 16

What are the two main types of scalar images?

Answer 16

1. Mean diffusivity
2. Fractional anisotropy

Question 17

What is mean diffusivity?

Answer 17

Average of all our individual measurements which is the average of the three orthogonal principle diffusion directions

Question 18

What is fractional anisotropy?

Answer 18

Tells us what the deviation is from the average, how stretched the ellipsoid is

Question 19

What are directional colour encoded images?

Answer 19

Coloured diffusion maps

These are usually fractional anisotropy maps with the overlaid colour indicating the principle diffusion direction

Question 20

What is one of the main clinical applications of diffusion?

Answer 20

Stroke - diffusion was found to be an early marker of stroke

Question 21

Why is DWI better than T2 imaging for stroke?

Answer 21

Diffusion is found to be reduced quickly within hours of stroke onset, due to cytotoxic oedema

Diffusion occurs before before it becomes visible on a T2-w image BUT with DWI it can be picked up in the image as a bright area from day 1

Question 22

Why might we have to be careful when interpreting DWI images of stroke?

Answer 22

After the initial dip in diffusion, diffusion recovers towards more normal values, eventually becoming elevated above normal due to vasogenic oedema

This means that although there is an initial fall in diffusion, we get a pseudonormalisation afterwards which is where the diffusion values are returned to normal but the brain tissue is still abnormal so we must be careful interpreting DWI images

Question 23

What is motion correction?

Answer 23

Motion correction involves using computational image registration to align all images in the diffusion dataset

Question 24

Why do we use motion correction?

Answer 24

As with fMRI, motion correction can significantly improve diffusion image quality

Question 25

What causes distortions in echo planar images?

Answer 25

EPIs are heavily distorted, particualry at tissue boundaries

This distortion depends on the polarity of the phase encode gradient “blips”

Question 26

How do we correct for distortions?

Answer 26

Susceptibility induced distortion correction

The difference between the positive phase encode blip and the negative phase encode blip is exploited by the FSL tool “topup” which corrects for the distortions

Question 27

What is tractography?

Answer 27

A brain imaging technique that describes the mapping of the location and direction of white matter bundles and their constituent fibers within the human brain

We use the DWIs to look at connectivity between different parts of the brain

Question 28

How can we carry out tractography?

Answer 28

If we’ve measured diffusion tensors in every single image and in every single voxel within the image, we can measure the principle eigenvectors

The principal eigenvector can be plotted at each voxel to give an indication of the major white matter fibre orientation.

Finding pathways through this vector field is the basis of tractography.

Question 29

What is streamline tractography?

Answer 29

Most simple method

Starting from a seed point, voxels are connected together using a tractography algorithm

The tract propagates until termination criteria are met

Question 30

What are the two termination critera for streamline tractography?

Answer 30

Angle between principal eigenvectors exceeds a certain threshold

Fractional anisotropy drops below a certain value

Question 31

What is a problem with streamline tractography?

Answer 31

A stream-line algorithm can be used to identify pathways within the vector field originating from a specified seed point

However, these algorithms only identify a single pathway and do not deal with branching fibres

They also give little indication of how likely the pathway is to be a true anatomical pathway

Question 32

How can we counter the issues with streamline tractography?

Answer 32

We can use our diffusion ellipsoid to decide how likely it is to go in a particular direction

Question 33

What are diffusion ellipsoids and profiles?

Answer 33

The diffusion ellipsoid represents the r.m.s. diffusion distance at a given snapshot in time.

The diffusion profile is calculated from the diffusion tensor using d(r) = rT D r and represents the diffusion measurement along the direction r.

Question 34

What can the diffusion profile be thought of as ?

Answer 34

An Orientation Distribution Function, where the function defines the relative likelihood of travelling in any given direction

Question 35

What is orientation distribution function sampling?

Answer 35

We draw samples from ODF
At each iteration, a sample is drawn from the ODF in each voxel
Each iteration produces a different vector field on which tractography can be run

Question 36

What is probabilistic tractography?

Answer 36

Streamline tractography is performed many times (>1000) with the ODF used to define the principal diffusion direction in each voxel for each run

The number of times a streamline passes through a voxel is counted and used to give a connection probability

Question 37

What are the limitations of the tensor model?

Answer 37

The single tensor / ellipsoid model is not good for describing voxels that contain multiple fibre populations, i.e. crossing fibres, etc

It models restricted diffusion in the plane of the crossing fibre with no preference being given to the two fibre orientations

It’s relatively simple to include more complex models into the tracking procedure, but they require more time consuming acquisitions (i.e. more directions / b-values)

Question 38

What is Region of Interest analysis?

Answer 38

Extract major white matter fasciculi using probabilistic tractography

Region of interest masks can be generated and summary diffusion parameters calculated for the tract (e.g. Mean Diffusivity, Fractional Anisotropy, Tract Volume)

Correlate diffusion parameters with clinical or cognitive investigations.

Question 39

What is an interesting application of tractography?

Answer 39

Cortical connectivity - to find connections between cortical regions, for example those activated by fMRI, or that exhibit abnormal cortical thickness

Unfortunately, this is an area where streamline-based algorithms perform poorly

Question 40

What is a method to assess cortical connectivty that overcomes the limitations of streamline-based algorithms?

Answer 40

Global tractography?

Question 41

What is global tractography?

Answer 41

Propagates a front from a seed point with the rate of front propagation F(r) determined by directional coherence of the ODF with front normal

An arrival time T(r) is assigned to each voxel r and is defined as the time at which the front crosses the voxel

Geodesic pathways can be calculated through the arrival time field by using a gradient descent algorithm

A connectivity metric “scores” the likelihood that a pathway is real.

Question 42

What is an important advantage of global tractography?

Answer 42

It gives you a way of connecting every seed point, you get a connection likelihood to every other point in the brain, unlike streamine algorithms where you start off at the seed point but it might break very quickly and you dont get a connection likelihood to every other point in the brain

Question 43

What is another advatage of global tractography in terms of penetration that can also be considered a limitation?

Answer 43

Global tractography is able to penetrate much deeper into the cortex than local (streamline) methods e.g. deep white matter seeding

This captures as much of the tract as possible but, penetrating deeply can also increase measurement error

Question 44

What is voxel based morphometry using fractional anisotropy?

Answer 44

Became popular to use VBM to identify voxel-wise differences between groups based on their fractional anisotropy signal maps

Align FA images to a template

Get the FA images in a standard space

Then blur them to make them more compliant

The we do GLM to calculate a t-statistic that we can then threshold to see whats different between groups or see what regions correlate

Question 45

What were the limitations of VBM analysis?

Answer 45

Results from VBM analysis were found to be highly dependent on the registration

No existing non-linear registration algorithm was capable of accurately aligning the complex white matter tract structures between subjects

Thus, many false positives were identified on VBM analysis due to misregistration

Results were also found to be highly dependent on the degree of spatial smoothing applied to the images- No consensus on what the amount of smoothing should be

Question 46

What method was developed to overcome the limitations of VBM?

Answer 46

Tract based spatial statistics

Question 47

What are tract based spatial statistics?

Answer 47

Bring in FA images
Register them to the standard template
But then take an average map, skeletonise it and then we threshold that skeleton map
This is essentially producing a map of the fibres that are most consistent between subjects and we then project our fractional anisotropy values back onto that skeelton and then we just do our statistics on the skeleton
It essentially overcomes the registration issue

Its essentially the VBM equivalent for diffusion