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 0-470-84641-066Positron Emission Tomography (PET)Peter F. Liddle 1 and Cheryl L. Grady 21 University of British Columbia, Vancouver, British Columbiaand 2 Rotman Research Institute, Toronto, Ontario, CanadaPositron emission tomography (PET) provides quantitativeimages of the function of the brain in life. It generates an imageof the distribution of a radioactively-labelled tracer substance thatis distributed in the brain according to its pattern of physiologicalactivity. By appropriate choice of tracer substances, it is possibleto measure physiological variables such as blood flow, metabolism,neurotransmitter receptors, presynaptic neurotransmitterpools and aspects of amino acid metabolism.The essence of any tomographic technique is a mathematicalreconstruction of a two-dimensional image of the distributionof some physical variable (e.g. concentration of radioactivity),from a set of measurements of the value of that physicalvariable, averaged along a large number of intersecting straightlinepaths through the brain. The feature that distinguishesPET from single photon emission computed tomography(SPECT) is the fact that a PET camera detects the pairedphotons generated by positron annihilation. When a positron isemitted from the tracer substance, it is annihilated by collisionwith an electron in the surrounding matter. This annihilationgenerates two g-ray photons, which each have an energy of511 keV and must travel in opposite directions. When twophotons are detected simultaneously in different crystalsarranged in a ring around the head, it can be concluded thata positron annihilation event has occurred at some point alongthe straight line connecting the two detectors. This use ofcoincidence detection of pairs of photons to determine thedirection of travel of the photons is intrinsically more efficientthan the use of collimators to determine the direction of travel,as is necessary in SPECT. Furthermore, correction forabsorption in the brain tissue is straightforward in PET studies,because the amount of absorption along the straight-line pathbetween a pair of detectors can be measured directly in apreliminary transmission scan, using a ring source. It is thuspossible to quantify the local concentration of the positronemittingisotope in the brain in absolute terms.The positron-emitting isotopes used in PET are 15 O [half-lifefor radioactive decay (T/2) 2 min]; 13 N (T/2, 10 min); 11 C (T/2,20 min); and 18 F (T/2, 110 min). The relatively short half-life ofpositron-emitting isotopes presents a logistic problem, since thePET camera must be located near to the cyclotron required toproduce the isotopes. However, an advantage of short-livedisotopes is that the rapid decay of radiation minimizesunnecessary radiation exposure after the procedure is completed.In addition, in the case of 15 O, it is possible to carry outmultiple separate PET scans within a single session ofinvestigation, allowing the measurement of changes in brainfunction in response to various mental or pharmacologicalstimuli.PET TRACER SUBSTANCESIn principle, virtually any substance involved in physiologicalprocesses that can be labelled with a positron-emitting isotopemight be used in PET, but quantitative measurement requires anadequate mathematical model of the processes governing distributionof the substance in the brain.An image of regional cerebral blood flow (rCBF) can beobtained from the distribution of intravenous [ 15 O]H 2 O which isdelivered to the brain at a rate depending on cerebral perfusion.Inhaled [ 15 O]oxygen provides an image of oxygen distribution inbrain tissue which, when combined with an rCBF image, can beused to generate an image of regional oxygen metabolism(rCMRO 2 ). Intravenous [ 18 F]deoxyglucose (FDG) can be usedto provide an image of regional glucose metabolism (rCMRGlu).This technique relies upon the fact that deoxyglucose istransported into cells by the same mechanism as is responsiblefor glucose uptake, but its metabolism is arrested after the firstreaction in the glycolytic pathway. Hence, deoxyglucose accumulateswithin cells at a rate which reflects the rate of entry of glucoseinto the glycolytic pathway.The development of labelled ligands that are suitable formeasuring the characteristics of neurotransmitter binding sites is adifficult task, because of the difficulty in achieving a high level ofspecific binding at tolerable doses of the ligand. An example of awell-behaved ligand is [ 11 C]raclopride, which binds to D2dopamine receptors 1 . It associates and dissociates rapidly fromreceptors, so that equilibrium is established relatively quickly,making it possible to determine an equilibrium binding curve.From such a binding curve, it is possible to determine the strengthof binding (KD) and the density of receptors (B max ). Other ligandsthat have been used to study neurotransmitter function include[ 11 C]SCH 23390 for D1 dopamine receptors 2 ,[ 11 C]WAY-100635 3to measure 5-HT 1 serotonin receptors, and [ 18 F]altanserin 4 and[ 18 F]setoperone 5 for measurement of 5-HT 2 receptors.SOURCES OF VARIATION IN PET IMAGESIf an imaging technique is to be useful for delineating pathologicalprocesses, it is necessary that the variation in image due to thepathological process of interest should not be swamped byPrinciples 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