Analysis, Tractography and Applications in Diffusion Imaging

Question 1

What can be exploited by diffusion MRI?

Answer 1

Entire white matter tracts which can be several millimetres across, often have a coherent orientation in any particular part of brain

Question 2

What is magnetic resonance signal sensitive to?

Answer 2

Random thermal motion of water molecules within neural tissue

Since structures such as cell walls and myelin impede such motion, observing the characteristics of this self-diffusion in a particular part of brain provides insight into the underlying tissue microstructure

Question 3

What confers a strong orientiental dependence of anisotropy on the mobility of free water ?

Answer 3

Very linear structure of white matter tracts

Question 4

When are water molecules freer to move along cyclinders than across them?

Answer 4

Very loosely, a millimetre or so of tract may be thought of as resembling a bundle of cyclinders with a single orientation

Question 5

What does MR brain diffusion utilise?

Answer 5

The principle of microscopic water movement in the brain tissue

Under normal conditions, water in the brain tissue moves rather freely. When a disruption to the blood supply of the brain occurs, the tissue will swell

The swelling will decrease the freedom with which the water can move about

The restriction in movement is visible on the MT diffusion scan images

Question 6

What is diffusivity in the brain?

Answer 6

1. Mean diffusivity which can be collected from ADC analysis
2. Get bright area In the centre of the brain at the surface of cerebrospinal fluid where the diffusivity is high
3. Dark areas in the remaining areas

Question 7

What are we interested from tractography?

Answer 7

Anisotropy

Question 8

What do we want to get the orientation of?

Answer 8

White matter structures

Question 9

Why do we rely on the anisotropy of diffusion?

Answer 9

We can’t see the white matter structures directly

Question 10

What is found in CSF?

Answer 10

Relatively equal freedom to move in all directions

Question 11

What is fractional anisotropy?

Answer 11

A scalar value between zero and one that describes the degree of anisotropy of a diffusion process

A value of zero means that diffusion is isotropic I.e. it is unrestricted (or equally restricted) in all directions

A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions

Question 12

What is FA thought to measure in diffusion imaging?

Answer 12

1. Fiber density
2. Axonal diameter
3. Myelination in white matter

Question 13

What occurs in structured spaces?

Answer 13

The probability of water diffusion is constrained in some directions but unconstrained in others

Question 14

What happens in brain tissue?

Answer 14

Water molecules diffuse more freely along the axons but are relatively constrained from escaping it or moving across the walls of axons

Question 15

How can the diffusion tensor be calculated?

Answer 15

By calculating the diffusivity along multiple directions and it becomes possible to estimate the orientation of axon bundles

Question 16

What does white matter have?

Answer 16

Relatively high FA

Question 17

What do CSF and grey matter have?

Answer 17

Low FA

Question 18

What are the basis of anisotropy in tissue?

Answer 18

1. Neural white matter, arranged in bundles of fibres, is particularly linear
2. Diffusion perpendicular to bundles is more impeded
3. Myelin and neural filaments contribute

Question 19

What does anisotropy reflect?

Answer 19

Microstructure

Question 20

What is diffusion MRI in the clinic?

Answer 20

1. Effective diffusivity is affected by oedema or the presence of tumours
2. Diffusion MRI widely used in acute ischaemic stroke
3. Effects visible earlier in diffusivity map than in T2-weighted images
4. Also used to monitor tumour progression and response to treatment

Question 21

What is voxel-based analysis?

Answer 21

1. Whole-brain group contrast analysis can be used to find differences between patients and control, or correlations

Question 22

What are two features used in voxel-based analysis?

Answer 22

1. SPM - applicable with care, but may not be ideal for FA maps
2. TBSS - designed for use with DTI data: uses an FA “skeleton”

Question 23

What is the FA colour map?

Answer 23

1. Red for left-right
2. Green for anterior-posterior
3. Blue for superior-inferior
4. Orientation only, no information about direction

Question 24

What is not obvious on structural image?

Answer 24

What is the effect on the white matter

Has the white matter taken over destroyed by the tumour or has the tumour moved things out of the way

Question 25

What is vector FA map?

Answer 25

Superimpose principal direction vector

Question 26

What can anisotropic be described by?

Answer 26

Mathematical tensor

Question 27

What can diffusion be summarised as?

Answer 27

1. MD | 2. FA maps

Question 28

What is tractography?

Answer 28

A technique that allows to identify fibre bundle tracts by connecting voxels based on the similarities in maximal diffusion direction

Question 29

What is principal directions?

Answer 29

The direction in which there is greater diffusivity in each voxel There is flow across the corpus callosum and follow other tracts similarly Use this information and follow to reconstruct white matter tracts

Question 30

What are streamlines?

Answer 30

To track through diffusion data, the track command requires seed points from which to initiate streamlined These seed points are defined in an image that is in the same physical space as the diffusion data, but not always in the same voxel space For example, your seed image could be of 1mm resolution, while your diffusion data is of 2mm resolution. But the physical space of both images should be aligned, even though the voxel indices are not.

Question 31

What is the process of streamline?

Answer 31

1. Begin at seed point 2. Find the principal direction. 3. Step a short distance 4. Repeat until termination (leaving white matter or brain, excessive curvature, length limit, too little anisotropy

Question 32

What is tractography?

Answer 32

1. Follow principal directions in contiguous voxels to reconstruct fibre tracts 2. Anatomically coherent bundles of fibres can be grouped together 3. Allows visualisation, segmentation and analysis of brain connectivity 4. Group analysis of FA/MD within specific tracts a common alternative to VBA

Question 33

What are the two types of tractography ?

Answer 33

1. Deterministic | 2. Probabilistic

Question 34

What is deterministic tractography?

Answer 34

A point estimate of the principal diffusion direction at each voxel is used to draw a single line

Question 35

What is probabilistic tractography?

Answer 35

Provide a probability distribution on the diffusion direction at each voxel ( the higher the distribution, the higher the uncertainty of connections in that area) which is then used to draw thousands of streamlines to build up a connectivity distribution

Question 36

What are the advantages of probabilistic tractography?

Answer 36

1. Allows to continue tracking in area of high uncertainty (with very curvy tracts) 2. Provide a quantitative measure of the probability of a pathway being traced between two points

Question 37

What is noise and uncertainty?

Answer 37

Tracking process accumulates local errors Trajectory can jump from one fasciculus to another Probabilistic; gives a sense of these effects

Question 38

What are the problems with probabilistic tractography?

Answer 38

1. Various sources of uncertainty mix together 2. Streamlines fall away with distance from the seed point 3. Not reliable as a measure of connectivity 4. Spurious branches may occur

Question 39

What are used of ROIs?

Answer 39

1. Typically, handawn 2. Used to constrain the tracking to say we are only interested in a subset of streamline 3. Can have false positives or under estimation of the tracts

Question 40

What are more complex ROI constraints?

Answer 40

1. Several ROI types may be needed for consistent results 2. Waypoint, termination and exclusion masks are common 3. ROIs not easily transferred between subjects and/or populations 4. But “recipes” can be transferred

Question 41

What are applications of tractography?

Answer 41

1. White matter mapping and tract segmentation 2. Studying effects of lesions, rumours etc 3. Planning surgery and assessing recovery 4. Feeds into neuronavigation along with structural and functional imaging

Question 42

What are development and aging?

Answer 42

1. Brain continues to develop after birth and throughout childhood 2. Developmental processes in white matter include: myelination, synaptogenesis, and synaptic pruning 3. FA generally increases and MD decreases with age; tracts vary together 4. Some small gender differences in certain age ranges 5. Opposite effect during aging

Question 43

What are limitations of diffusion MRI and tractography ?

Answer 43

1. Relatively low image resolution (2-3mm voxels) 2. Complex relationship to tissue microstructure 3. Sensitive to damage, but not very specific (degeneration, inflammation, oedema) 4. Cannot tell direction of communication 5. Tractography works best in major tracts 6. False positive/negative connections

Question 44

What are limitations of DTI?

Answer 44

1. DTI is diffusion MRI + tensor model 2. Extremely useful method, providing information about white matter orientation and “integrity” 3. But if two fibres cross within a voxel then lamda1 ~ lamda 2 > lamda 3 and there is no true principal directions (oblate ellipsoid) 4. More recent approaches can model the signal in the presence of 2+ fibre populations

Question 45

What are improved models and HARDI?

Answer 45

1. Greater angular resolution (I.e. more directions) and less restrictive assumptions than in DTI produce more convincing results 2. Subject to diminishing returns 3. Greater b-value also often used when fitting these models 4. Multiple fibre directions observable 5. Can result in more true positives, but also more false positives

Question 46

What is the crossing-fibre problem?

Answer 46

1. The diffusion tensor cannot represent multiple fibre orientations within a single image voxel 2. But in real data these are very common 3. People try to overcome the problem using more sophisticated models (e.g. multiple tensors) or taking up a model-free approach (q-space imaging)

Question 47

What is structural connectivity graphs?

Answer 47

1. Weight of a connection between cortical region (e.g.) the number of streamlines connecting the two 2. Can also be derived from correlations in cortical thickness or grey matter volume