Summary: With the use of positron emission tomog raphy (PET) and the 150 steady-state- [ISF]fluorode oxyglucose combined method, the local interrelationships between the cerebral metabolic rate for oxygen (CMR02) and the cerebral metabolic rate for glucose (CMRGlc) were investigated in control subjects and in stroke pa tients. In addition to the classic in vivo autoradiographic approach, a kinetic method was used to measure CMRGlc because it was expected to be more reliable in cerebral ischemia. In control subjects local coupling be tween CBF, CMR02, and CMRGlc was confirmed, and acceptable values for the CMR02/CMRGlc ratio were found; the latter, however, was lower in white matterThe recent development of independent methods for measuring in the human brain the rates of ox ygen consumption (CMR0 2 ) and glucose utilization (CMRGlc) using positron emission tomography (PET) has revived the study of the coupling be tween CMR0 2 and CMRGlc, previously restricted to the whole brain only (Finkle stein et aI., 1981; Baron et aI., 1982; Rhodes et aI., 1982). Such in vivo studies may help us understand better the con ditions required for the occurrence and the prog nostic significance of enhanced anaerobic glycol ysis in cerebral ischemia.Address correspondence and reprint requests to Dr. Baron at Service Hospitalier Frederic Joliot, CEA Departement de Biol ogie, 91406 Orsay, France.Abbreviations used: CBV, Cerebral blood volume; CMRGlc, cerebral metabolic rate for glucose; CMR02, cerebral metabolic rate for oxygen; CT, computerized tomography; GlcAV, arterio venous glucose difference; ICA, internal carotid artery; MR, metabolic ratio; OEF, oxygen extraction fraction; OM, orbito meatal; PET, positron emission tomography.140 than in gray. Uncoupling between CMR02 and CMRGlc was observed in all stroke patients, suggesting that (1) enhanced anaerobic glycolysis occurred both in reper fused recent infarcts and in chronically ischemic tissue, and (2) substrates other than blood-borne glucose were being oxidized at the borders of recent infarcts. However, methodological uncertainties presently make such obser vations only tentative. Finally, a coupled depression of CMRO, and CMRGlc was found in the contralateral cer ebellu m . Key Words: Cerebral glucose utilization-Ce rebral oxygen consumption-Oxygen-IS -Positron emission tomography. METHODS AND PATIENTS MethodsThe steady-state oxygen-IS method of measuring CBF and CMR02 (Jones et aI., 1976) was combined with the [ISF]fluorodeoxyglucose eSFDG) technique for measuring CMRGlc (Phelps et aI., 1979; Reivich et aI., 1979). A detailed account of the combined measurement has been given earlier (Baron et aI., 1982). Briefly, consecutive continuous inhalation of trace amounts of CI502 and 1502 was performed first. Once completed, 16 min (eight pe riods) were allowed to elapse before rapid (=20 s) intra venous injection of IsFDG (3-8 mCi). Generally, three contiguous head levels, parallel to the orbitomeatal (OM) line, were studied. The coincidence photons were col lected by an EC...

Brain protein synthesis may be evaluated in vivo by a PET three compartment methionine model. 14 human brain tumor patients were studied. Protein synthesis rate (PSR) was increased in any glial tumor even in low grades, but this increase was statistically more important in anaplastic tumor. Radiotherapy action was evaluated in two patients. Local tumoral PSR was reduced to normal brain PSR after treatment. No difference was seen in normal cortex contralateral to the lesion between pre and post radiotherapy examination. 11 C-L-Methionine incorporation measured by PET looks as a very sensitive method for studying tumor metabolism and treatment effects.

Treatment of gliomas remains disappointing in spite of a great number of experimental biological data and of randomized therapeutic studies. This could be partly explained by the inefficiency of our conventional methods to assess the regional metabolism of these tumors. The use of positron emission tomography (PET) brings encouraging possibilities in this field. We report our preliminary experience of measuring regional cerebral methionine uptake with PET after intravenous injection of [11C]L-methionine. Twenty-two patients with histologically confirmed gliomas were studied. An ECAT II positron emission tomograph was used for scanning. The position of the plane was chosen to include a major section of the tumor in the reconstructed brain slice. The protocol required a two-step examination: 1) after injection of 15 to 25 mCi of [11C]L-methionine, 12 scans were performed over a period of 46 minutes; and 2) 18 hours later, regional cerebral blood volume was measured in the same slice after intravenous injection of 2 to 4 mCi of 68GaCl3. The tumoral region of interest was determined as being the area of maximum activity. For each patient we calculated the ratio, R, between the activity in this tumor region of interest and the activity in the contralateral healthy symmetric region of interest which was used as an "internal standard" for the same patient. We correlated the ratio R with the histological grading. In 22 patients, mean values of R were calculated for each tumor: Grade II (n = 5): R = 1.04 +/- 0.27; Grade III (n = 5): R = 1.68 +/- 0.22; and Grade IV (n = 12): R = 2.33 +/- 0.86.(ABSTRACT TRUNCATED AT 250 WORDS)

SUMMARY Using the '8f-fluoro-2-deoxy-d-glucose technique and positron emission tomography (PET), the local cerebral glucose utilisation (lCMRGlc) was measured in four non-demented patients with early-onset, bilateral Parkinson's disease characterised by the predominance of akinesia. The study was done twice, first in the untreated condition, and then after levodopa had been resumed. Despite a marked clinical improvement, we found no alteration in lCMRGlc between the first and second studies in any of the brain structure analysed. Compared to control values, lCMRGlc in the basal ganglia was moderately increased in both studies. These essentially negative findings agree with most previous human or animal studies, and indicate that the functional alterations in the central dopaminergic systems of patients with Parkinson's disease have metabolic correlates that are too small to be demonstrated by current PET devices.The typical symptomatic triad of Parkinson's disease, that is akinesia, rigidity, and tremor, implies that functional alterations take place in certain cerebral structures. Since energy metabolism in the brain has been shown to be coupled to function,' changes in regional energy mnetabolism specific to the functional abnormalitves of Parkinson's disease might be expected to occur. Such changes should be found in the structures deprived of their normal dopaminergic afferences, principally the striatum2 and the cortico-limbic areas3 and, as a secondary effect, in the structures receiving projections from these structures.In the attempt to use local energy metabolism as a marker of disordered dopaminergic transmission systems, several studies of the local cerebral glucose utilisation (lCMRGlc) using '4C-2-deoxy-D-glucose ('4CDG) autoradiography in rats with unilateral destruction of the dopaminergic systems have failed to show any consistent pattern of changes,4-9 although some reported striking alterations.4 5 Human studies of Parkinson' s disease patients have been, for methodological reasons, restricted to 2-dimensional '33xenon regional cerebral blood flow (rCBF)'0-'2 or Address for reprint requests: JC Baron, MD, Service Hospitalier Fr6d&ric Joliot,

Treatment of gliomas remains disappointing in spite of a great number of experimental biological data and of randomized therapeutic studies. This could be partly explained by the inefficiency of our conventional methods to assess the regional metabolism of these tumors. The use of positron emission tomography (PET) brings encouraging possibilities in this field. We report our preliminary experience of measuring regional cerebral methionine uptake with PET after intravenous injection of [11C]l-methionine. Twenty-two patients with histologically confirmed gliomas were studied. An ECAT II positron emission tomograph was used for scanning. The position of the plane was chosen to include a major section of the tumor in the reconstructed brain slice. The protocol required a two-step examination: 1) after injection of 15 to 25 mCi of [11C]l-methionine, 12 scans were performed over a period of 46 minutes; and 2) 18 hours later, regional cerebral blood volume was measured in the same slice after intravenous injection of 2 to 4 mCi of 68GaCl3. The tumoral region of interest was determined as being the area of maximum activity. For each patient we calculated the ratio, R, between the activity in this tumor region of interest and the activity in the contralateral healthy symmetric region of interest which was used as an “internal standard” for the same patient. We correlated the ratio R with the histological grading. In 22 patients, mean values of R were calculated for each tumor: Grade II (n = 5): R = 1.04 ± 0.27; Grade III (n = 5): R = 1.68 ± 0.22; and Grade IV (n = 12): R= 2.33 ± 0.86. Correlations between hypermetabolism and grading are highly significant for Grades II/III (P = 0.0045) and II/IV (P = 0.00019), but not for Grades II/IV (P = 0.3141). We assessed the effects of radiotherapy: in 3 glioblastomas studied before and after radiotherapy, a significant decrease of R was observed: from 2.84 ± 1.43 to 1.35 ± 0.05. In one Grade II glioma, there was no change. Last, we assessed the early effects of intra-arterial chemotherapy: 8 patients were studied before and after the first course of treatment with an intracarotid injection of 1,3-bis-(2-chloroethyl)-l-nitrosourea (BCNU). Early modifications of R were correlated with clinical evolution after completion of treatment (intracarotid BCNU every 6 weeks). Despite a patient in whom a dramatic decrease of R was followed by a long survival with normalization of the computed tomographic scan, no significant correlation could be displayed between modifications in R and the length of survival. This approach will have to be developed in future studies.