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shown that voxel-based analysis of SPECT blood flow studies, specifically of the difference
between ictal and inter-ictal cerebral blood flow as a Z-score of the interscan variation of
SPECT scans, was more accurate than just thresholding the subtraction images132.

Ictal SPECT may be useful as a non-invasive presurgical method of investigation by
optimising the placement of intracranial electrodes to define sites of seizure onset, but there
must be caution as the technique may identify sites of seizure spread, rather than the site of
onset133. Ictal 99mTc-HMPAO scans must always be interpreted with caution. Simultaneous
video-EEG is essential to determine the relationship between the onset of a seizure and tracer
delivery; without this there is the risk of confusing ictal and post-ictal data. Further, spread
to other areas of the brain, such as the contralateral temporal lobe, may occur within seconds
of seizure onset and so an image of cerebral blood flow distribution 12 minutes after the
onset of a seizure may indicate other than the site of onset.

Until recently, 99mTc-HMPAO had to be constituted immediately prior to injection, resulting
in a delay of up to one minute. A preparation has now been developed which is stabilised
with cobalt chloride. This allows the labelled tracer to be prepared in advance and injected
into a patient at any time over the subsequent six hours. The advantage of this development
is that the interval between seizure onset and tracer delivery to the brain can be significantly
reduced. An alternative is to use ready constituted 99mTc-ECD, or bicisate, which is stable for
several hours, may be injected within 220 seconds of seizure onset and demonstrates a focal
increase in CBF134. The interval between seizure onset and injection may also be shortened
by the use of an automated injection device that may be activated by the patient when they
detect the beginning of a seizure135,136. Extratemporal seizures may be very brief, increasing
the need for injection of blood flow tracer as soon as possible after the start of a seizure. With
the inevitable interval between injection and fixation of the tracer in the brain, however, it
may not be possible to obtain true ictal studies.

In conclusion, inter-ictal SPECT imaging of CBF is only moderately sensitive and ictal
SPECT improves the yield. The place of the investigation is in the presurgical work-up of
patients with refractory partial seizures and normal MRI scans, in order to generate a
hypothesis that may then be tested with intracranial EEG recordings.

POSITRON EMISSION TOMOGRAPHY STUDIES OF CEREBRAL BLOOD
FLOW AND GLUCOSE METABOLISM

Positron emission tomography (PET) may be used to map cerebral blood flow, using 15O-
labelled water, and regional cerebral glucose metabolism using 18F-deoxyglucose (18FDG).
PET produces quantitative data with superior spatial resolution to SPECT. PET data should
always be interpreted in the light of high quality anatomical MRI, providing a structural-
functional correlation. The development of programmes to coregister MRI and PET datasets
on a pixel-by-pixel basis has been fundamental to making these correlations. Statistical
parametric mapping has been shown to be useful in the evaluation of 18FDG-PET scans for
clinical purposes, with the advantages of allowing a rapid and objective evaluation137. In
addition, quantitative analysis of data, with correction for partial volume effects add a further
useful dimension to the analysis, and this is facilitated by the use of a template to objectively
delineate multiple volumes of interest51.

An epileptogenic focus, studied inter-ictally, is associated with an area of reduced glucose
metabolism, and reduced blood flow that is usually considerably larger than the pathological
abnormality. Comparison of 18FDG-PET scans with 11C-flumazenil (FMZ) scans138-140
indicate that neuronal loss is confined to a more restricted area than the region of reduced
metabolism.
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