Mohammed T. Abou-Saleh

Principles and Practice of Geriatric Psychiatry.Editors: Professor John R. M. Copeland, Dr Mohammed T. Abou-Saleh and Professor Dan G. BlazerCopyright & 2002 John Wiley & Sons LtdPrint ISBN 0-471-98197-4 Online ISBN 0-470-84641-067Single-photon Emission Computerized Tomography(SPECT)Mohammed T. Abou-Saleh 1 and D. P. Geaney 21St George’s Hospital Medical School, London, UK, and 2 Warneford Hospital, Oxford, UKThe introduction of single-photon emission computed tomography(SPECT) has markedly enhanced the study of brain function.The development of SPECT was the culmination of a series ofinvestigations of cerebral blood flow (CBF) pioneered by Ketyand Schmidt 1 in the late 1940s, combined with the introduction oftransmission computed tomography (CT) in the early 1960s, inwhich three-dimensional images are derived from two-dimensionaldata. This chapter provides a review of the principles andbasic techniques of SPECT, its present utility and application toclinical practice.PRINCIPLES AND TECHNIQUESKety and Schmidt 1 pioneered CBF studies in man using nitrousoxide as a diffusible agent. These early studies required inhalationof nitrous oxide and sampling of arterial and internal jugularvenous blood and could only provide a measure of whole-brainblood flow. Techniques to measure regional rCBF followed andused freely diffusible radionuclides, such as 85 krypton and133 xenon, which were injected into the carotid artery 2 . 133 Xenonemits g-radiation, which can be detected through the intact skull,and multiple scintillation probes allow the measurement of CBFin specific regions of the brain. Further technological advances indetector sensitivity and data analysis allowed the replacement ofintra-arterial injections by intravenous infusions or inhalation ofgaseous 133 Xe, so that the measurement of rCBF became a noninvasiveprocedure. The rCBF data were initially presented in twodimensions and essentially reflected cortical flow, but with thedevelopment of the tomographic technology for SPECT, a threedimensionalmeasurement of rCBF could be obtained. Theradiotracers used in SPECT emit a single g-ray (or photon), asopposed to the dual simultaneous g-rays of PET radiotracers, andhence the term ‘‘single-photon’’.Recently, new radiotracers labelled with 123 iodine and99m technetium have been introduced. These lipophilic radiopharmaceuticalscross the blood–brain barrier and distribute inproportion to the rCBF shortly after intravenous injection. Theyare trapped in the brain and have a stable or static distributionover time, unlike freely diffusible, dynamic radiotracers such as133Xe, enabling images of higher resolution to be obtained. Theseagents can be used with the conventional rotating g-cameras thatare widely available in most nuclear medicine departments,whereas 133 Xe-labelled agents are not. The most advancedSPECT systems are now capable of a resolution of 8 mm andimaging times as short as 2–3 min for rCBF.Unlike PET, there is no current prospect of SPECT being ableto provide a direct measure of regional cerebral metabolism.However its use to measure neurotransmitter receptors is anevolving technique. The radioligand 123 I,3, quinuclidinyl 4-iodobenzilate (QNB) has been developed for the measurementof muscarinic acetylocholine receptors and has been applied to thestudy of Alzheimer’s disease 3 .NORMAL SUBJECTS AND NORMAL AGEINGDynamic tomographic studies with 133 Xe produce similar valuesfor grey matter flows as found with PET, but substantiallyoverestimate white-matter rCBF and consequently give a limiteddistinction between grey and white matter. Static tomographicstudies with 123 I- and 99m Tc-labelled radiotracers cannot, as yet,provide an absolute measure of rCBF, but the pattern of rCBF,which can be expressed semiquantitatively, is similar to that foundin PET studies, and the resolution is better than with 133 Xedynamic tomographic studies.The pattern of rCBF reported in normal subjects reflects, atleast in part, the conditions of the subjects at the time. Forexample, if subjects are studied with eyes open, the visual cortexhas the highest individual rCBF, but if the eyes are closed, therCBF is reduced 4 . At present there are no generally acceptedstandard conditions for the control or resting state but it is clearthat these should be standardized in any individual study.CBF is reduced in relation to both advancing age andprogressive cerebrovascular disease, and hypertension is themost important predisposing factor for a significant reduction inCBF.The reduction in rCBF with age is confined to the grey matter—the white matter is unaffected and is more marked in anteriorcortical regions. Females have higher rCBF than males forsubjects up to 60 years of age, but the difference lessens above thisage.In the normal individual at rest, the rCBF is closely coupled tothe regional metabolism of glucose and oxygen and is felt toreflect the underlying cerebral function. PET studies have shownthat during visual stimulation, the rCBF and metabolic rate ofglucose have similar marked focal increases in the visual cortex,while the regional cerebral metabolic rate of oxygen has a muchsmaller increase 5 . This uncoupling of glucose uptake and oxygenmetabolism suggests that most of the extra glucose taken upduring physiological stimulation is not oxidized and presumablylactate production by glycolysis increases. The implication ofPrinciples and Practice of Geriatric Psychiatry, 2nd edn. Edited by J. R. M. Copeland, M. T. Abou-Saleh and D. G. Blazer&2002 John Wiley & Sons, Ltd