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Positron Emission Tomography
Positron Emission Tomography Imaging in Dementia
a report by
Karl Herholz
Director, Wolfson Molecular Imaging Centre, and Professor of Clinical Neuroscience, University of Manchester
Positron emission tomography (PET) utilises biologically active molecules in (language impairment in the dominant and visuospatial disorientation in the
micromolar or nanomolar concentrations that have been labelled with short- sub-dominant hemisphere). In contrast to other dementia types, in AD
lived positron-emitting isotopes. The physical characteristics of the isotopes glucose metabolism in the basal ganglia, primary motor and visual cortex
and the molecular specificity of labelled molecules, combined with the high and cerebellum is usually well preserved. This pattern generally reflects AD
detection efficacy of modern PET scanners, provide sensitivity for in vivo clinical symptoms, with impairment of memory and associative thinking,
measurement that is several orders of magnitude higher than with the other including higher-order sensory processing and planning of action, but
imaging techniques. While the very short half-lives of
15
O (two minutes) and relative preservation of primary motor and sensory function.
11
C (20 minutes) limit their use to fully equipped PET centres with a cyclotron
and radiopharmaceutical laboratory,
18
F-labelled tracers (half-life 110 Voxel-based comparisons with normal reference samples clearly show that
minutes) can be produced in specialised cyclotron centres for regional the posterior cingulate gyrus and the precuneus are also impaired at an early
distribution to hospitals running a PET scanner only. stage of AD.
7
This is usually not directly obvious by mere inspection of FDG
PET scans because metabolism in that area is above the cortical average in
Glucose is the main energy supply for the brain. Its metabolism maintains normal brain at a resting state,
8
and with the beginning of impairment it
ion gradients and glutamate turnover and is closely coupled to neuronal returns to the level of the surrounding cortex but does not stand out as a
function at rest and during functional activation.
1
Its measurement by
18
F-2- hypometabolic lesion. Thus, this important diagnostic sign is easily missed by
fluoro-2-deoxy-D-glucose (FDG) is based on phosphorylation of the tracer by standard visual interpretation of FDG PET brain scans. On the background of
hexokinase, which is the pivotal first step of that metabolic pathway. sufficient numbers of FDG PET scans in normal controls it is becoming
Typically, PET images are obtained 30–60 minutes after tracer injection, increasingly standard to base the interpretation of patient studies not merely
when FDG uptake is approximately proportional to glucose metabolism, and on visual interpretation of the tracer distribution, but also on quantitative
actual measurement times can be as short as five to 10 minutes. Under mapping with reference to an appropriate normal sample.
9–15
resting conditions (awake, but without external stimulation), normal grey
matter displays two to four times higher glucose metabolism than white The pattern of metabolic impairment can vary considerably among individual
matter. There is a moderate reduction of cerebral glucose metabolism with patients. It is typically more pronounced in patients with onset of the disease
age, mainly affecting the frontal association cortex.
2
Significant regional before 75 years of age than in patients who develop AD at later ages.
16,17
The
reductions of glucose metabolism indicate impairment of synaptic function, degree of metabolic impairment in frontal association cortices varies and is
and the technique is therefore applicable to all types of dementia. typically seen in more severely affected patients and in patients who are
carriers of the apolipoprotein E4 allele.
18
There are AD patients with very
There is growing interest in imaging amyloid deposits, the pathological pronounced focal impairment of occipito-temporo-parietal association areas,
hallmarks of Alzheimer’s disease (AD). There are now several PET tracers which may correspond to the clinical syndrome of posterior cortical atrophy.
19
for in vivo amyloid imaging that allow longitudinal studies of amyloid
deposition to clarify whether amyloid deposition is a cause or consequence Normal ageing and AD cause significant atrophy, including in those brain
in the pathophysiology of AD.
3,4
Furthermore, the degeneration of areas that are also hypometabolic on FDG PET.
20
Regional atrophy will cause
major neurotransmitter systems can be demonstrated in vivo by using underestimation of regional glucose metabolism on PET scans due to partial
appropriate PET tracers. Impairment of the cholinergic and dopaminergic volume effects, depending on scanner resolution. The magnitude of this
neurotransmission is of particular diagnostic interest. By these means, PET effect has been estimated in several studies. They concluded that the
can detect early stages and differentiate between various types of dementia, metabolic reduction in posterior neocortical association areas cannot be
and also monitor progression and the effect of therapeutic intervention. explained completely by atrophy-related partial volume effects,
21
while there
Alzheimer’s Disease
Karl Herholz is Director of the Wolfson Molecular Imaging
Over more than 20 years, multiple studies have demonstrated that glucose
Centre and a Professor of Clinical Neuroscience at the
metabolism and blood flow are impaired in temporal–parietal association University of Manchester. Previously, he worked at the Max-
cortices, with the angular gyrus usually being located at the centre of the
Planck Institute for Neurological Research in Cologne, as a
research fellow at the National Institute of Health (NIH) in
metabolic impairment.
5
The frontal association cortex may also be involved,
Bethesda, Maryland, and as a Professor in Neurology at the
but variably and usually to a lesser degree. The affected association cortices
University of Cologne. Dr Herholz studied physics and
medicine at the University of Erlangen in Germany.
are those that become myelinated last during brain maturation and are also
prone to cortical amyloid deposition.
6
There may be a distinct hemispheric
E:
karl.herholz@manchester.ac.uk
asymmetry, which usually corresponds to the predominant cognitive deficits
© TOUCH BRIEFINGS 2008 109
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