Role Of DTI In Multiple Sclerosis Flashcards
What is the background of multiple sclerosis?
- Chronic disease
- Dissemination of lesions in time and space
- Areas of inflammation, demyelination, gliosis
What are 10-15% of the patients?
Primary progressive MS
No clear cut relapses at the beginning
What are pathological changes of MS lesions?
- Oedema
- Inflammation
- Demyelination
- Remyelination
- Axonal loss
- Gliosis
Why is that patients with high lesion loads are not necessarily disabled as those with low lesion load?
- There is damage occurring in the white matter next to lesion between cortex and lesions in NAWM
- There are changes that cannot be see with conventional imaging but observed in the most advanced form of imaging
What is diffusion tensor imaging?
Comprises a group of techniques where calculated eigen values (lamda 1,2 and 3G and eigen vectors (epsilon 1,2,3) are used to create images reflecting various diffusion properties of tissues
What is the sum of eigenvalues called?
The trace
What are the averages of eigenvalues called?
Mean diffusivity or apparent diffusion coefficient (ADC)
What is DTI?
MRI technique that provides information about random motion of water molecules in vivo
What can you construct?
A model of how water diffuses within each voxel/pixel unit in the brain
What is found in white matter?
Highly aligned nerve fibres
Water diffusion tends to occur along long axis of the nerve fibre and tends to be restricted in lamda 1 and principal eigen vector
Where is diffusion generally greater in white matter?
The direction parallel to he axons - diffusion anisotropy
Define anisotropic
Biological tissues are highly structured and typically have different diffusion coefficient along different directions
Why is white matter highly anisotropic?
Parallel orientation of its nerve fibre tracts
In anisotropic material what can diffusion not be described by?
Single number but a [ 3 x 3 ] array called diffusion tensor
How can tensor be represented?
3D shape where it will look like an ellipsis with lamda 1 indicating the long axis of diffusion
What an you derive from these eigen vectors?
Certain diffusion matrix which characterise tensor/model
What is fractional anisotropy?
A measure of the directionality of the diffusion
What has higher anisotropy?
Voxel of brain which show high directionality or high directional preference
What has low FA?
- Grey matter
2. CSF
What is axial diffusivity?
- Lamda 1
2. Magnitude of the diffusion along long axis of diffusion tensor
What is radial diffusivity?
- Average lamda 2 and lamda 3 diffusion perpendicular to the lamda 1 along long axis of diffusion
Why DTI?
- Changes in diffusion parameters reflect pathological changes in the tissue structure (e.g. membranes, subcellular structure)
- It detects pathological abnormalities that are not visible on conventional MRI such as those in NAWM
Where can region of interest be performed on?
- Map diffusivity
2. FA maps
When do we use region of interest?
- When the study is focused on particular part of the vein
- The area is easily defined
- Processing time is no an issue
Regions of Interest where we know where we want to look first, we can pre-define them apriori and work out different diffusion values within those areas - performed maps - construct maps of mean diffusivity and FA
What are the limitations of region of interest analysis?
- Multiple ROI require a correction for multiple comparisons
- Poor inter-observer reproducibility
- undertaker formal measurement of reproducibility
- define guidelines
What is ROI and tractography?
- Define a given tract in all subjects
- Calculate FA along tract
- Compare FA between subjects
What is the strength and problem of ROI in tractography?
- Strength: correspondence issue hopefully resolved
2. Problem: requires manual intervention to specify tract, hence doesn’t investigate whole brain
What is histogram analysis?
- Look at the whole brain and average and calculate the frequency distribution of diffusion matrix for region of brain - calculate frequency distribution
- Get mean values and peak location
- There is higher diffusivity value for patients with MS in NAGM
When to use histogram analysis?
- No a priori hypothesis exist about location of pathology
- Operator dependent bias is an issue
- Time is an issue
What are the limitations of histogram analysis?
- Information on the location of abnormalities is list
- Partial volume effect due to atrophy has statistically significant effect on all FA histogram variables
- Segmentation of DTI images is an issue
When to use VBM ?
- As an alternative to ROIs and histograms
- All locations across the brain are tested in an unbiased way
- Specific location of significant group differences or correlations is automatically shown
What are limitations of VBM-style analysis?
- Registration algorithm is an issue
2. Alignment difficult: smallest systematic shifts between groups can be incorrectly interpreted as FA change
What are aims to sort the problem of tract-based spatial statistics?
- Using a non-lunar registration software
2. Projection onto an alignment invariant tract representation
What can you create in White matter?
FA skeletons or FA template which generally represent white matter structure within brain
The lower the FA
The higher the disability
What do chronic lesions tend to have?
Lower ADC values
Where is there a large overlap between?
Chronic plaques and acute plaques
Statistical differences
To assess the efficacy of treatments
- Lack of standardisation of measurements for multi-centre studies
- The exact relationship between longitudinal changes pathological abnormalities is unclear
What is DTI sensitive to?
- Disease related changes that occur over time
2. It has the potential to be used in trials
What are the tissue types?
- MS lesions
- NAWM
- NAGM
What are features of MS lesions?
- Increase mean diffusivity and decrease FA
- Heterogeneity of values
- Highest degree of abnormalities in non-enhancing lesions
What did we learn from MS lesions?
- Different abnormalities (demyelination, oedema, inflammation)
- Axonal loss and gliosis in chronic lesions
What are the features of NAWM?
- Increase in mean diffusivity and decrease in FA
- Significant correlation between disability and FA or MD only in clinically eloquent regions
- Linked correlation with T2 LL
What did we learn from NAWM?
- DTI is sensitive to NAWM diffuse changes
- Regional NAWM measures correlate with disability (axonal loss and gliosis)
- Processes independent from T2 lesions
What are features of NAGM?
- Increase or = MD and decrease in FA
2. Poor correlation with T2 LL
What did we learn about NAGM?
- DTI sensitive to NAGM diffuse changes
2. NAGM measure correlate with Disability
What did patients with MS show?
Decrease in FA and increase in MD
Metrics in the cervical cord
(Axonal loss and gliosis) that correlates with disability
What is axial diffusivity best discriminator of?
Visual outcome
Still significant when adjusted for baseline acuity
What is low baseline AD associated with?
6 months
- worse acquity
- worse CS
- lower VEP
- Longer VEP
- thinner RNFL
What are the limitations of tractography ?
- Crossing fibres might represent an issue
- Tracking errors
- Lack of validation of tractography
Specific to MS:
1. Effects of lesions on the reconstructed tracts
How do we build a connectome?
- Structural image is divided into subregions
- Whole brain tractography is performed
- Parcellated image and tractography are compiled into a connectome
What are limitations of connectomics?
- Emerging field - no standardised pipelines
- Evidence of disconnection from a network perspective
- topology of WM lesions
- no longitudinal studios - Other approaches such as Grey matter networks and functional networks
What are the technical limitations of DTI?
- Relative long scanning time to obtain good SNR
- DW are sensitive to motion artefacts
- Effects of eddy currents
- Effects of susceptibility gradients (geometric distortion, signal drop-outs)
- Constraints in scanner hardware
Specific to MS:
1. Different pathological processes can result in similar diffusion changes (e.g. increase in MD to oedema, axonal loss, demyelination)
What is the clinical radiological paradox in MS?
The number of lesions that the patients have -lesion burden- doesn’t necessarily correlate with clinical conditions
What is DTI?
MRI technique that provides information about random motion of water molecules in vivo
What happens in the white matter?
Water diffusion is generally greater in the direction parallel to the axons
= Diffusion anisotropy
What happens in lamda 1 and principal eigen vector?
vector direction water molecule diffuses through
How can tensor be represented?
Three dimensional shape
Look like an ellipsoid
What does lamda 1 represent?
Long axis of the diffusion
What is the mean diffusivity?
Average
How much diffusion there is in that voxel
What is Fractional Anisotropy (FA)?
A measure of the directionality of the diffusion
What is an example of isotropic diffusion?
Water droplets
What does grey matter have?
Low Anisotropy
The microstructural architecture is not as coherent or organised as it is in white matter
What does CSF have?
Low FA
as diffusion happens in multiple directions at the same time
What is VBM-sytle analysis?
- Take brains of different people and warp them into a common space
- Map them to each other [all the voxels]
What occurs in demyelination?
Radial diffusivity goes up as a result of more inter-neuronal prespace for the water to diffuse
Axonal degeneration + demyelination
Reduction in the longitudinal diffusivity
