| Summary: | Magnetic resonance imaging (MRI) has become an invaluable tool for studying brain
and its associated pathologies. Multiple sclerosis (MS) is one such pathology and attempts
are being made to use MRI to characterise the myelination state of MS lesions.
Two techniques have been proposed which appear to be sensitive to myelination:
magnetization transfer (MT) and T₂ relaxation. Quantification of these techniques uses
magnetization transfer ratios (MTR) for MT and myelin water percentages for T₂ relaxation.
If the two techniques are both related to myelin content then they are expected to
be related to each other. It was found by in vivo MRI measurements that white matter
from normal volunteers and normal appearing white matter from MS patients had significantly
larger MTRs and myelin water percentages than grey matter. However, only a
weak correlation was found between MTRs and myelin water percentages in MS lesions
(R=0.5,P=0.005) indicating that each technique provides an independent measure of M S
pathology.
Since water in white matter resides in two main compartments, in intra/extracellular
spaces and between myelin bilayers, it was thought that MT would have a different effect
on each water pool. This was examined by combining a T₂ relaxation sequence, which
separates the two water pools, with an MT pulse. It was found using in vivo MRI measurements
on normal human white matter that the myelin water pool was significantly
more affected by an MT pulse than the intra/extracellular water pool (P=0.00001 to
p=0.04 for different white matter structures). It was also found that small offset frequencies
caused more direct saturation of the myelin water pool than the intra/extracellular pool resulting in different contrast. Finally, at long delay times between the MT pulse
and the initiation of the T₂ relaxation sequence (>500 ms), the difference in MT between
the two pools was eliminated indicating exchange within that timescale.
In vitro experiments on bovine brain were performed on a ¹H - NMR spectrometer. A
4-pool model was proposed to explain the different relaxation times measured in bovine
white matter. These pools included intra/extracellular water, myelin water, non-myelin
molecules and myelin molecules. Exchange between the myelin water and myelin, and
the intra/extracellular water and non-myelin molecules were rapid with the former being
slightly faster than the latter. There was no evidence for exchange between the two water
pools within the timescale of 1 s.
For human brain, a diffusion model was proposed to investigate exchange between
the water pools. Results showed that variations in parameters associated with the intra/
extracellular water pool affected only that pool. Variations in the myelin water pool,
however, influenced the relaxation times and amplitudes of both water pools. Finally, it
was found that changes in the axonal diameter and myelin thickness resulted in changes
in the myelin water percentages and T₂ relaxation times. This could account for some
of the differences in myelin water percentages and T₂ times measured in different white
matter structures in the human brain.
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