Using quantitative PET, the authors studied the binding of [11C]PK11195, a marker of activated microglia, in the thalamus of patients with chronic middle cerebral artery infarcts. All patients showed increased [11C]PK11195 binding in the ipsilateral thalamus, indicating the activation of microglia in degenerating projection areas remote from the primary lesion. A persistent increase in [11C]PK11195 binding suggests active, long-term thalamic microstructural changes after corticothalamic connection damage.

Using position emission tomography (PET) and equilibrium imaging with oxygen-15 labelled gases, the cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF) and oxygen consumption rate (CMRO2) were measured in multiple regions of interest over the cerebral cortex of 5 control subjects, 4 patients with strictly unilateral longstanding carotid artery occlusion, 1 patient with middle cerebral artery embolic stroke in the acute stage, and 4 patients with subcortical stroke and no cervical arterial disease. In each control subject, the regional CBV was linearly and positively correlated with both CBF and CMRO2, while the local mean transit time (t = CBV/CBF) was uniformly distributed, reflecting the local adaptation of both the vascular tone and the capillary density to the metabolic demand at constant cerebral perfusion pressure that characterizes the normal brain. In patients with subcortical stroke, cortical blood volume was reduced in proportion to the matched reduction in CBF and CMRO2, suggesting that the metabolic depression resulting from cortical deafferentation increases the resting tone of pial vessels. Unilateral carotid occlusion induced larger CBV and t, and steeper slopes of the CBV-CBF relationship, particularly on the occluded but also on the patent side. The assessment of the local cerebral perfusion pressure (CPP) as judged by the ratio CBF/CBV in 3 patients with focally raised OEF and preserved or reduced CMRO2, allowed the demonstration in multiple cerebral regions of single patients of two well-known physiological phenomena: the autoregulation of CBF, followed by the rise of the OEF as local CPP falls further. In addition, the depression of CMRO2 in the ischaemic cortex was associated with a trend for CBV to return towards normal values, compared with the maximally elevated CBV found in oligaemic but metabolically normal areas. This suggests that a process of metabolic vasoconstriction may participate, among other factors, in the vascular collapse that occurs, and would serve to regenerate some haemodynamic reserve, at very low CPP levels.

These data indicate that circumscribed frontal dysfunctions may occur in chronic alcoholic subjects before clinically obvious neurological complications, and may account for some of the alcohol-related neuropsychological and behavioural impairments.

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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...

N-(llC) methyl, N-(methyl-1 propyl), (chloro-2 phenylj-1 isoquinoleine carboxamide-3 (PK 11195) o r ( l l C ) MPCI was synthetized in a short time (45 min) and high s p e c i f i c a c t i v i t y (769 Ci/mmol) for the positron emission tomography of peripheral benzodiazepine receptors in heart, kidney and brain. The precursor used was the N-desmethyl MPCI (PCI). The radioactive reagent was the ( l k ) methyl iodide obtained from nuclear reaction 14N ( p , a ) 11C vit: 11CO2 and 11CH30H. The chemical p u r i t y of the end-product was checked, a f t e r HPLC p u r i f ication, by chemical ionisation mass spectrometry i n the para1 l e l synthesis of cold MPCI. The methylation, reversed phase HPLC p u r i f i c a t i o n , evaporation times were 10, 6 min respectively so t h a t s t e r i l e and i s o t o n i c i n j e c t a b l e solution o f ( l k ) MPCI ready f o r use may be obtained, i n l e s s t h a n 45 min a f t e r the end of nuclear bombardment.

Lesions causing so-called rubral tremors frequently involve the substantia nigra or the nigrostriatal fibers, suggesting dopaminergic denervation as possibly contributory. We examined this hypothesis using PET and [18F]-fluorodopa in six patients with a contralateral tremor following a peduncular lesion. The denervation revealed by PET was even more marked than in severe parkinsonian patients. All patients showed partial to complete improvement with levodopa therapy. PET evaluation of D2-receptors with [76Br]bromolisuride showed no asymmetry of the D2 binding despite the important asymmetry of 18F-fluorodopa uptake. Our results indicate an important involvement of the nigral dopaminergic system in peduncular tremors that appears to be independent of postsynaptic dopamine receptors.