THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES SPECIAL FEATURE Positron Emission Tomography in Movement Disorders

Positron emission tomography provides a method for the quantitation of regional function within the living human brain. Studies of cerebral metabolism and blood flow in patients with Huntington's disease, Parkinson's disease and focal dystonia have revealed functional abnormalities within substructures of the basal ganglia. Recent developments permit assessment of both pre-synaptic and post-synaptic function in dopaminergic pathways. These techniques are now being applied to studies of movement disorders in human subjects. RESUME: La tomographic par emission de positrons dans les desordres du mouvements La tomographie par Amission de positrons (PET scan) est une m6thode de quantification des fonctions regionales dans le cerveau humain vivant. L'erude du mdtabolisme c6r6bral et du flot sanguin chez des patients souffrant de chorde de Huntington, de maladie de Parkinson et de dystonie focale montre des anomalies fonctionnelles a l'inte>ieur meme des sous-structures des noyaux gris centraux. Des ddveloppements regents permettent d'6tudier les fonctions prd et post-synaptiques dans les voies dopaminergiques. Ces techniques sont maintenant utilisdes pour l'6tude des ddsordres du mouvement chez l'humain. Can. J. Neurol. Sci. 1985; 12:6-10 Positron emission tomography (PET) is a method which is used to measure the concentration of positron-emitting radiopharmaceuticals in the human brain in vivo. The use of this technique in conjunction with appropriate labelled compounds and tracer kinetic models enables the quantitation of regionally selective biochemical and physiological processes in health and disease. This review is divided into two parts. The first section deals with the methodology which is in routine use at a number of PET centres for the measurement of cerebral metabolism and blood flow, and clinical studies which have been performed using these methods in patients with movement disorders. The second section deals with PET techniques which have been developed more recently to study functions in dopaminergic pathways in man. CEREBRAL METABOLISM AND BLOOD FLOW The major energy expenditure in the brain is utilised by ion transport mechanisms for pumping sodium and potassium across neuronal membranes to maintain the electrochemical gradients necessary for the generation of action potentials (Mata et al., 1980). Aerobic glucose metabolism is responsible for the bulk of the necessary energy production. Therefore, the mapping of regional cerebral glucose metabolism (CMRG) or oxygen metabolism (CMR02) provides a functional image of brain activity. The approach which has been used with PET for CMRG measurement is based on the C-2-deoxyglucose (DG) autoradiographic method developed by Sokoloff and co-workers (1977) for use in animals. This method depends on the following unique properties of DG. The bidirectional transport of DG across the blood brain barrier and its initial hexokinase-catalyzed phosphorylation is similar to that of glucose. Unlike glucose, however, the product of this reaction (DG-6-phosphate) cannot be metabolized further and is essentially trapped within the tissue. Dephosphorylation by g4ucose-6-phosphatase does occur, but only very slowly. The accumulation of DG-6-P in the tissue is therefore directly related to the rate of DG phosphorylation by hexokinase. An operational equation has been derived (Sokoloff et al., 1977) which expresses glucose consumption per unit mass of tissue in terms of measurable variables. This method has been used extensively with tissue autoradiography in animals for the measurement of regional CMRG in both physiological and pathological studies (for review see Sokoloff, 1981). As originally designed, this method required direct measurement of the regional radioactivity concentration in the brain after DG administration and therefore could not be applied to This paper is based on a special lecture presented at the Fifth Dystonia Workshop held in Calgary, Alberta on February 9-10, 1984 From the Division of Neurology, Health Sciences Centre Hospital, University of British Columbia, Vancouver Reprint requests to: Dr. Wayne Martin, Division of Neurology, Health Sciences Centre Hospital, University of British Columbia, 2211 Wesbrook Mall, Vancouver, B.C., Canada V6T1W5 LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES man. The development of PET, however, made it possible to make these measurements noninvasively. Reivich et al. (1979) demonstrated the use of this model for CMRG measurements in man with PET and the tracer F-fluoro-2-deoxyglucose (FDG) which behaves in a similar fashion to DG. The Sokoloff model was subsequently extended to include the dephosphorylation reaction which was found to be significant for the later times employed with PET measurements (Phelps et al., 1979; Huang et al., 1980) . This model is now utilized for in vivo measurements of CMRG in man in numerous. PET centres throughout the world. Cerebral oxygen extraction may be measured using inhaled 0-labelled oxygen. Two major approaches have been developed for this measurement. A steady-state approach with continuous tracer inhalation has been widely used (Jones et al., 1976; Subramanyam et al., 1978; Frackowiak et al., 1980). More recently, an approach which combines the data obtained from PET measurements of cerebral blood flow and blood volume with that from a single breath inhalation of O0 has been described and validated (Mintun et al., 1984). With either of these techniques, cerebral oxygen utilization is calculated from the extraction, the measured regional cerebral blood flow, and the arterial oxygen content. CLINICAL STUDIES OF MOVEMENT DISORDERS