Uses Of MTR In MS Flashcards
What are the current MRI measures ?
- Lesion load on T1 and T2 weighted scans
- Atrophy
- Enhancing lesions [BBB leakage - some inflammation]
What is MTR not specific to?
Biophysical processes such as demyelination or remyelination
- Inflammatory lesions
- Oedema
- Gliosis
- Axonal damage
What does MTR fail to measure?
Normal appearing tissue damage
In MS, what happens beyond the lesion?
There is further damage e.g. diffuse damage
develop quantitative measure that take into account these changes that are outside the lesions
What is MTR?
More quantitative measure that relates to tissue macromolecular structure [relates to myelin in the CNS]
What is a major structural component in white matter?
Myelin
Where has correlations been found?
demyelination and remyelination
What is MTR sensitive to?
Early disease abnormalities
MTR
Feasible to implement and is available on most clinical scanners
How do we measure signal from conventional MRI?
Protons in relatively free environments
-Intra- and extra-cellular water
What are the other compartments that exist in WM and GM tissue?
- Macromolecules, water trapped within myelin layers [myelin water]
- Proteins attached to macromolecules have signal decay too rapid to be observed directly using conventional MRI
- But they exchange magnetisation with other proton compartments
- Use that to measure them indirectly
What is the “two pool model?”
Macromolecules - restricted proteins —> surface —> bulk water
At the periphery there is Dipolar interaction which causes chemical exchange then distributed by diffusion
How can magnetisation be exchanged between two pores?
Distributed by diffusion to the bulk water protons
What are the features of free protons?
- Mobile
- Fast moving
- Relatively long T2 (~50ms)
- Produces conventional MR signal
- Narrow spectrum of resonant frequencies (~20Hz)
What are features of restricted protons?
- Immobile
- Slow moving
- Very short T2 (~10-20microseconds)
- Invisible on conventional MRI
- Very broad line in spectrum (>10kHz)
What is the equation for MTR?
Acquire same sequence twice
100 (Su-Ss)/Su
What are the characteristics of MTR?
- Measured in percent units (pu)
- Can be used to investigate tissue structure
- Is “semi-quantitative”
Define semi-quantitative
- Pulse sequence and irradiation dependent
2. Sensitive to errors in setting the flip angle and B1 field non-uniformity
Why does MTR tend to be reduced in lesions?
There is loss of structure e.g. macromolecular protons
- loss of myelin
- increase in water content
What are examples of analysis of MTR data?
- Region-of-interest (ROI) analysis
- Analysis of average MTR
- Histogram analysis [Look at whole brain - all voxels]
- Voxel based statistical analysis
What is ROI analysis?
Used to study individual lesions or region in NAWM or GM to obtain information of regional changes in MTR
Automatic lesion segmentation software being developed
For ROI analysis, where was significant difference observed in?
Selenium of corpus callosum in secondary progressive MS
Reduction in thalamus
Larger MTR reductions in secondary progressive than the other groups
What is done before segmentation into different types of GM and WM?
Lesion filling
What is histogram parameters?
- Look at all the VOXELS in the brain or NAWM or particular region of brain
- Histogram is a frequency distribution that shows a number of pixels with a particular MTR value
- Peak location is the most representative MTR - modal MTR
- In MS, the MTR is reduced and therefore peak location will be shifted to the left and there is an increase in variations in a lot of MS patients
What did the analysis of MTR data show for histogram parameters?
- Low MTR in lesions
- NAWM peak position lower in SP than controls
- NAGM peak position lower in SP than RR
What is voxel-based morphometry?
- Co-register all of the images onto a template [Reduces the major differences between brains] - different anatomy between different people - smooths the data
- Each voxel is an average of itself and it’s neighbours
- Measure atrophy on 3D T1
- There are region where atrophy and MTR overlap but there are also regions where MTR is reduced prior to the volume loss
What does MTR reflect?
- Axonal loss
2. Damage to myelin
What is MTR largely dependent on?
Macromolecular density of cell membranes and phospholipids
What does low MTR reflect?
Reduced capacity to exchange magnetisation between the 2 pores - Reduction in the bound pore protons
What are GM MTR reductions likely to reflect?
Decrease in size and number of neurons and dendritic density
What are WM MTR reductions likely to reflect?
Myelin (myelin lipid such as cholesterol and sphingomyelin) changes and/or reduced axonal density
What does MTR imaging allow us to probe?
Myelin in vivo
How can MTR be accessed indirectly?
Making measurements related to amount of exchange taking place between free and restricted pools
What can MTR be used to monitor?
Progression of disease and effects of treatment as it is sensitive to demyelination and remyelination
What depends on the density of macromolecules?
Degree of signal loss in the presence of MT saturation
What is it important to distinguish between?
MT weighted and MTR images
Within MT weighted image ?
- Within WM: highest MTR values are found in the corpus callosum
- White matter contains more myelin than Grey Matter
Within MTR map
- Higher MTR values are found in WM than GM
2. Within GM, highest MTR values are found in thalamus
What does reduced MTR mean?
- Reduced capacity of free protons to exchange magnetisation with bound proton pool
- MTR as low as 0 in CSF (due to the absence of macromolecules)
- Low MTR reflects tissue damage
What is MTR correlated strongly with?
Axonal density within and outside lesions
What does MTR reflect?
Myelin content
And less strongly with axonal count
What is MTR sensitive to at 3T?
Cortical demyelination in ME
Low MTR
- Homogenous enhancing lesions
- Enhancing lesions only observed with triple dose of Gd, not subtle dose (I.e. less inflammatory leisons)
- Lesions that enhance for 1 month (not as old as chronic lesions)
- Small enhancing lesions
Very low MTR
- Ring lesions - older (chronic demyelination) - core
- Enhancing lesions observed with single dose of Gd
- Lesions that enhance for 2 or more months (older)
- Large enhancing lesions
What lesions are observed on T1-w?
Isointense (pre-Gd) lesions
What lesions are observed on T2w MRI?
Hyperintense
Very low MTR lesions
Hypointense lesions
- black holes on T1w MRI
What correlation is observed on post-Gad T1w images (best for non enhancing lesions)
Correlation between MTR and signal intensity
Where are greater MTR abnormalities found?
Perilesional NAWM
The periventricular MTR gradient
- Occurs early
- Independent of WM lesions
- Is associated with subsequent risk of developing MS by 2 years
- Is associated with subsequent risk of developing disability by 5 years
For the analysis of average lesion MTR, where is there a reduction larger in?
Relapsing Remitting than Benign MS
What does reduction in MTR mean?
- Reductions in the bound protons
- Reduction in the marcomolecular content
- Increase in water content
What can MTR be used for?
Monitor the progression of MS and are useful in clinical trials
Within WM, where is the highest MTR values found in?
Corpus Callosum
Within GM, where is the highest MTR values found in?
Thalamus
What is found in the outer cortex?
Subpial cortical GM lesion
What are Enhancing lesions?
- Observed with Gadolinium
- BBB has been compromised
- Inflammation
