Magnetisation Transfer Theory, Measurement and Analysis Flashcards
What is mainly given by protons in relatively free environments: intra- and extra-cellular water?
The signal measured with conventional MRI
What are the other compartment that exist in WM and GM tissue?
- Protons attached to macromolecules, or in water trapped within myelin layers
- Protons attached to macromolecules have a signal decay too rapid to be observed directly with MRI
- But they exchange magnetisation with other proton compartments
What was first described by McConnell; modified by Edzes and Samulski?
- Two-pool Bloch model
2. Binary spin bath model
What displays different behaviour under RF excitation?
Protons in tissue exist in two ‘pools’/compartment
What is free proton pool?
Proton mainly in water
What is bound (‘restricted’) proton pool?
- Protons bound to macromolecules
2. ‘Semi-solid’ environment
What are features of free protons (in water)?
- 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)
- Invinsible on conventional MRI
- Very broad line in spectrum (>10kHz)
What tissues exhibiting MT effect?
- Myelinated white matter
- Grey matter
- Muscle
- Blood
- CSF
What does CSF have?
only free protons and no bound protons [not much of an MT effect]
What are the 3 pool models?
- Myelin
- Myelinated axons
- Intra and extra-cellular water
- Biologically more meaningful
What has the symbol Su?
Free protons pool when unsaturated
- tall very narrow line in the spectrum centred at omega 0 [Larmor frequency]
What has a more broader spectrum but still with the central Larmor frequency?
Semi-solid pool
Where is the off-set frequency from?
Central resonance frequency
What happens when RF pulse is applied?
The free protons are not affected but the bound semi solid pool are affected - this leads to saturation of the macromolecular pool
What does saturation mean?
Moving the protons out the longitudinal plane into the transverse plane
What is the consequence of protons constantly exchanging?
Its reduction in the semi-solid pool tries to balance itself out with the free proton pool
How is the reduction compensated ?
Magnetisation from free pool is transferred to the semi-solid pool
What does off-resonance irradiation mean?
Apply an RF pulse at W Larmor frequency
What is selective saturation of the macromolecular pool?
Saturation is transferred to the free pool via MT exchange
- Reduction of the MRI signal
What are the 2 parameters that control the MT-weighting?
- MT pulse power
2. Offset frequency
How can you minimise direct saturation of free pool?
Choose omega off
Why was continuous wave irradiation used previously?
Impractical in vivo due to hardware limitations, SAR restrictions and the fact that the MT pulse must be turned off for imaging
Why is pulsed irradiation more common?
- Well-defined RF pulse (known bandwidth)
2. Off resonance frequency chosen to minimise direct saturation of free pool
What does binomial pulses have?
Relative flip angles in proportion to a binomial sequence, with delays in between to allow free precession of magnetisation
What is on resonance saturation: binomial pulses
Net flip angle of 0 º
Can be exploited to selectively excite certain spins on basis of their T2 value or frequency
Apply a set of RF pulses with different amplitudes and signs
What does free protons have?
Very long T2
Magnetisation flipped into the transverse plane
«_space;T2
magnetisation flipped back again.
No net effect on longitudinal magnetisation
What does restricted protons have?
Very short T2
Magnetisation flipped into the transverse plane
»_space; T2
magnetisation dephases before it can be returned to the longitudinal axis.
Longitudinal magnetisation decreases i.e. signal is ‘saturated
What is the advantage of binomial pulses technique?
is very time-efficient (binomial pulse durations are typically < 3 ms), and causes a large signal reduction
What is the disadvantage of binomial pulses technique?
there is intrinsic direct saturation associated with the technique caused by the poor Fourier Transform profile of the pulses, therefore it is not so widely used now.
How do we use the MT effect to investigate
tissue?
Contrast manipulation – 1 image
Magnetisation Transfer Ratio (MTR) – 2 images
With/without MT saturation pulses
‘semi-quantitative’ (sequence dependent and affected by e.g. B1,T1)
Or ‘quantitative Magnetisation Transfer’ (qMT) – Many images
Fit quantitative model to data
Gives a set of parameters related to tissue structure
e.g. relative sizes of proton pools, exchange rates etc
Clear biological meaning – can also potentially be related to pathology
What can off-resonance pulse affect?
Free protons as well as the restricted proton pool
What does the free proton pool have?
Range of resonant frequencies
What happens if the MT pulse is close to the free proton peak?
It will be affected
What is MT pulse power?
A function of its amplitude and duration (width)
What may longer pulses have?
Narrower bandwith
may reduce direct saturation
What does direct saturation reduce?
The free pool magnetisation and therefore the signal seen
- Results in an artifically high MTR
- Not a result of the MT effect
What does saturation of restricted pool cause?
Signal intensity decreases in free pool
T1 decreases in free pool. (to T1sat (= T1 in the presence of MT saturation))
What is the intensity of MT weighted image Ss?
is a NOT a physically meaningful parameter
is pulse sequence and irradiation dependant
(but is related to tissue structure)
can be found from 1 MR image
What does T1sat describe?
describes return to equilibrium after saturation of bound protons
Technically defined as after complete saturation
Related to T1, but reduced by MT saturation
Can’t perform complete saturation in vivo due to SAR restrictions
Can be a useful parameter as
kf=MTR/T1sat
Where kf is the rate constant for transfer of magnetisation from free->bound pool
What is MTR equation?
MTR = 100 (SU-SS)/SU
What are the features of MTR?
measured in percent units (pu)
can be used to investigate tissue structure
is ‘semi quantitative’
pulse sequence and irradiation dependent
sensitive to errors in setting the flip angle and B1 (transmit) field non-uniformity
can be calculated from 2 MR images
What is Forward rate constant Kf?
- physically meaningful parameter
- related to tissue structure
- can be calculated from2 (or more) MR images e.g.
- long TR, unsaturated
- long TR, saturated
- Short TR, saturated
- Needs complete saturation
What is quantitative MT (qMT)?
Quantitative MT (qMT) has been developed as an extension of MT methods
Uses multiple images with different “MT weightings”
Vary MT pulse amplitude and/or offset frequency
Fit a more complex model of biological tissue to data
Extract a number of more fundamental parameters
Several variations on the method (and models)
Morrison& Henkelman 1995
Initial experiments on MT – Morrison & Henkelman 1995 Agar gel (2%, 4%, 8%) Bovine white matter 27 offset frequencies (14 Hz - 213 kHz) 7 irradiation powers (4 T - 125 T) Duration of MT pulse: 7 s - continuous wave (CW) MT To ensure steady state had been reached Room temperature (20 - 22 C)
What are the parameters in Henkelman’s model?
The parameters derived:
RB, RMoB/RA, R, 1/RAT2A and T2B
are NOT pulse sequence and irradiation dependant
can be calculated from 6 or more MR images
with a separate measurement of T1 (T1obs), the restricted proton pool fraction f can be calculated (Ramani 2002)
Acquisition: Pulse Sequences for MTR
Any pulse sequence can have MT irradiation added but to avoid confounding influences we need
proton density weighting
long TR Spin Echo
long TR/low flip angle (spoiled) Gradient Echo
MTR depends on pulse sequence timings e.g. TR/TE etc.
Tend to avoid Fast type sequences (as in FSE)
Each echo has different TE so magnetisation evolution very complex
Also some contrast in FSE is from incidental MT due to large number of (180°) pulses and SAR is already high
What does MTR also depend on?
irradiation (MT) pulse shape sinc, gaussian amplitude/duration/apparent flip angle ~10-20uT / 2-10ms / ~500-1000° repetition rate TR′ (time between MT pulses) determined by TR and number of slices for 2D sequence (TR’ = TR for 3D sequences) ~20-100ms between MT pulses
Why is MTR semi-quantitative?
Depends on a lot of sequence parameters (not easy to replicate across scanners/manufacturers)
Also on e.g. T1 weighting, errors in B1
Image quality can be variable
Hardware-related issues
What are the reasons for performing qMT?
As mentioned before the MTR is heavily sequence dependent
Sequences are hard to match, particularly across manufacturers
MTR is approximately proportional to f, T1A and kf (=RM0B)
Henkelman RM et al. NMR Biomed. 2001; 14:57–64
So if f decreases and T1 increases the MTR may be less sensitive
Morrison and Henkelman
Continuous wave MT technique
Uses a varying number of pulse amplitudes and offset frequencies but generally uses >100 MT weightings
Morrison C, Henkelman RM Magn. Reson. Med.33;475-482;1995
Morrison C et al. J. Magn. Reson. Series B108:103-113;1995
The Henkelman model has been modified for in vivo studies
Sled JG, Pike GB. Magn. Reson. Med. 46:923–931;2001
Tozer D et al. Magn. Reson. Med. 50:83-91;2003
Ramani A & Tofts PS. Proc. ISMRM 2000:8;2078
Pulsed MT used
Use CWPE as defined previously by Ramani
What are alternative methods for qMT?
Selective Inversion Recovery (SIR) methods
Gochberg & Gore. Magn Reson Med 57 (2): 437-41; 2007
Selectively invert free pool magnetisation & fit to a biexponential T1 model
SIR uses only low-power pulses & requires no separate RF (B1) or static field (B0) field maps
Analysis largely independent of macromolecular pool lineshape
SSFP methods
Gloor et al. Magn Reson Med 60:691–700; 2008
Generally quicker (short TR) with good SNR – although separate T1 and T2 estimates are also needed
Vary flip angle or pulse duration to affect MT contrast (loss of steady state due to MT)
Again estimates similar parameters from model
What are choice of MT pulse parameters?
MT pulse must be offset to avoid direct saturation ~1 kHz min offset
Close enough to affect bound protons ~ 100kHz max offset
Strong enough to give a reasonable MT effect ~ 300-800° flip angle
Weak enough to avoid SAR limits – particularly at 3T
Power and offset will interact
For qMT need to use more than 1 power
~10-20 data points in clinically feasible time
Good spread of data
E.g. 2 powers 7 frequencies spread ~250 °, 500 °, 1kHz-20kHz
Spinal cord
Technical challenges: Motion Size of cord Therefore we often want: High resolution Interleaved image slices (motion insensitive) and/or co-registration techniques
Optic nerve
Technical challenges Motion Size of nerve Fat & CSF contamination We want: High resolution Fat saturation CSF suppression Interleaved
What are examples of spinal cord conditions?
Multiple sclerosis
Adrenomyeloneuropathy
Neuromyelitis optica (NMO)
What are examples of optic nerve?
Optic neuritis
Multiple sclerosis
Neuromyelitis optica (NMO)
What is Magnetisation Transfer in controls?
MTR very precise -> can use normal WM for QA
Higher in WM (varies with location in brain)
MTR linked to myelin
MTR changes as the brain develops (myelination)
Engelbrecht V et al. Am J Neuroradiol 19:1923–1929;1998
70 children age 1 week 80 months
MTR changes from ~13-19 pu in young demyelinated brain
Up to 34-37 pu in older children
R2 (MTR vs. age) 0.6-0.96 dependent on location
What are MTR reductions in MS?
MTR reduction in MS lesions and NAWM in MS patients compared to controls (e.g. Filippi et al.,1994)
Demyelination & remyelination
Remyelination can be extensive even at early stage (e.g. Prineas et al Ann Neurol (1993) 33:137-51)
Gliosis
Oedema
Axonal Loss
Axonal tissue contributes to MTR effect
What are important points for MTR reductions in MS?
MTR reduced by reduction in f Destruction of bound protons OR increase in free water In MS earlier inflammatory stage & later chronic demyelination Same is true of f specifically Inflammation more likely to resolve
