The talk
was divided into three parts. The first part recapped previous studies which
were done using 1.5 T MRS. The second part went over a recent MRS study
which was done using the highest field strength ever, 3T, used in ME studies
and the third part discussed a recent pilot structural MRI study which also
used the field strength of 3T.
The
previous three studies ( Puri et al 2002, Chaudhuri et al 2003, Tomoda et al
2000) all found elevated free choline in the brain of ME patients. The
studies by Puri et al. and Chaudhuri et al. were systematic comparison
studies and Tomoda et al. published a non systematic case series of three
juvenile sisters with ME compared to a database on non matched controls.
This is
relevant in respect of infectious aetiology. The structure of outer cell and
organelle membranes are composed of two layers - lipid bylayers. Polar head
groups are often choline and it has occurred to some researchers that if one
suffers from certain infections then some organisms are able to prevent
cells from biosynthesising. Therefore one can’t produce sufficient
quantities of phospholipids and this would lead to the rise of free choline
and this has been measured by the three 1.5 T MRS studies.
The
second part of the talk discussed a recent proton neuro spectroscopy study
by Puri et al. using 3 T field strength. Based on preliminary evidence of
oxidative stress the question was how does this manifest in the brain itself
as well as in the periphery. It has been hypothesized that glutathione (GSH)
particularly might be reduced. On the other hand an Australian study has
found no significant difference between patients and controls (Richards,
Roberts et al. 2000). Nevertheless the hypothesis is still there that one
could find reduced GSH and this would be associated with increased blood
brain barrier (Bested et al).
The great
thing about proton neuro spectroscopy at 3 T is that one can open up the
field and see a large number of peaks. The peaks are fitted mathematically
in a way so one can work out the levels of GSH. This is what was done, 64
signal averages were used and there was careful optimisation of magnetic
field homogeneity both globally and in terms of the voxels being looked at.
The
result is while the mean value of glutathione seems to be lower than that in
gender and age matched controls, 2.7 versus 5.2, taken into account the
higher variants of standard deviation of the control group data there was in
fact no significant difference. These data are consistent with the
erythrocyte GSH results from the Australian study.
Finally
professor Puri talked about a pilot structural MRI study also at a field
strength of 3 T on 26 essentially severe ME patients. He decided to use a
technique called voxel based morphometry because this is a very fair way of
assessing whether or not there are changes between voxels between the two
groups. It is rather important because a lot of this is single handed study.
He knew who belonged to which group. Totally unblinded in that sense and had
to find a method which was particularly operator independent. The groups
were dicotomized into two age, gender and ethnicity matched groups and
professor Puri used his intial T1 weighted sagittal MRI scans which were
acquired early on at each protocol.
The data
images have to be transformed on to a standard space and a non linear
transformation is the method of choice these days so he constructed a MRI
template and produced a suitable statistical design. Registration (mapping
of one set of data to another accurately) method used Affine registration
which is a fair and appropriate way of doing this. Cluster based correction
for multiple comparisons was also used. The whole thing was also randomised
with 5000 permutations making it highly robust.
Results:
Grey matter areas which were less dense in ME patients compared to age and
gender matched controls: R inferior frontal gyrus, cingulate gyrus, L
precentral gyrus, L middle frontal gyrus and cerebellum.
In
conclusion:
- There are
clear biochemical and structural brain changes in ME.
- These
strongly argue in favour of a biological basis of this neurological disease.
- Further
detailed biological biochemical and neuroimaging studies are clearly
warranted.
