Regional Metabolic Activity Research Articles

The metabolic pathology of the AIDS dementia complex.

A progressive dementing illness, the AIDS dementia complex (ADC) is the most frequent neurological complication of the acquired immunodeficiency syndrome. Characteristic alterations in regional cerebral metabolic rate for glucose (rCMRGlc), associated with the presence or progression of ADC, were demonstrated by [18F]fluorodeoxyglucose/positron emission tomography in 9 of 12 patients with ADC compared with 18 normal volunteer subjects. In these 9 patients, two distinct patterns of regional metabolic activity were highly correlated with intersubject gray matter rCMRGlc variation and with disease severity as assessed by neuropsychological testing. Relative subcortical (thalamus and basal ganglia) hypermetabolism was characteristic of early ADC, and disease progression was accompanied by cortical and subcortical gray matter hypometabolism.

Conjunctival oxygen tension monitoring.

The adequacy of tissue oxygenation in any anatomic region is dependent both on the perfusion and the oxygen content of the blood perfusing that site. These two variables are integrated in the calculation of oxygen delivery (DO2), which represents the product of arterial oxygen content (CaO2 = [1.36 · Hgb · SaO2] + [0.003 · PaO2]) and cardiac index (CI). In addition, oxygen concentration in peripheral tissues will be dependent on regional metabolic activity and oxygen consumption, as well as local differences in vascular resistance and blood flow.

Brain organization in schizophrenia.

Brain metabolism was measured with positron emission tomography and [11C]deoxyglucose during baseline and during a visual task in 12 normal subjects and 18 schizophrenic patients. Global measures of metabolism for 11 brain regions were transformed into relative values by dividing them by the metabolic value for whole brain. Factor analysis was accomplished on the matrix of intercorrelations among the relative regional values for the normal and for the schizophrenic patients under baseline and under the task. Four factors that revealed independently varying metabolism in frontal, occipital, left-versus-right hemisphere, and subcortical structures were obtained. The frontal and subcortical factors discriminated between normal subjects and schizophrenic patients, whereas the occipital factor discriminated between baseline and task. Although activity in these individual regions varied significantly, it was the pattern of differences in regional metabolic activity that best discriminated between diagnostic groups and testing conditions.

Regional metabolism of experimental brain tumors.

Experimental brain tumors were produced in rats by stereotactical implantation of various neoplastic cell lines (RG 2, RG1 2.2, G 13/11, F 98, RN 6, B 104, and E 367). Using autoradiographic, bioluminescence, and fluoroscopic methods, the following regional hemodynamic and metabolic parameters were measured on intact brain sections: blood flow, glucose utilization, pH, and the tissue content of ATP, glucose, and lactate. Tumors exhibited a considerable diversity of regional blood flow and metabolic activity which did not correlate with the implanted cell line, location, or growth pattern. In solid regions of tumors the most consistent finding was a higher glucose utilization rate, a higher lactate, and a higher pH than in the surrounding brain tissue. Tumor ATP was slightly higher and glucose slightly lower than in the brain. In large spherical tumors a declining gradient of blood flow, glucose, and ATP from the periphery to the central parts was frequently observed, the decline being more pronounced for glucose than for ATP. In regions with high ATP tissue pH was usually higher than in the brain, but it decreased in areas in which ATP was depleted. The results obtained indicate that tumors are able to control tissue pH despite increased glycolysis and lactate production, as long as the energy state is not impaired. The mechanisms of pH regulation, therefore, have to be considered for establishing therapeutic procedures which intend to lower tumor pH for induction of tissue necrosis.

Subcortical changes in the regional uptake of [3H]-2-deoxyglucose in the brain of the monkey during experimental choreiform dyskinesia elicited by injection of a gamma-aminobutyric acid antagonist into the subthalamic nucleus.

Hemichorea/hemiballismus was induced in monkeys by localized injections of a gamma-aminobutyric acid antagonist into the contralateral subthalamic nucleus. During active dyskinesia, [3H]-2-deoxyglucose was administered and, subsequently, regional cerebral metabolic activity was examined by autoradiographic exposure of brain sections. The results indicate that during dyskinesia there was an overall decrease in local cerebral glucose utilization in a number of structures on the side of the brain contralateral to the abnormal movements (ipsilateral to the drug injection). These structures included the injected subthalamic nucleus, both medial and lateral segments of the globus pallidus, the substantia nigra, and the ventral anterior and ventral lateral nuclei of the thalamus. On the basis of evidence that changes in the energy requirement of neurons are due mainly to changes in synaptic activity, the autoradiographic findings are interpreted as indicating that during experimental hemichorea/hemiballismus there was an overall decrease in synaptic activity of subthalamopallidal, subthalamonigral and pallidothalamic pathways on the side of the brain contralateral to the dyskinesia. This interpretation is discussed in relation to current theories of the pathophysiology of choreiform dyskinesias.

Evaluation of the cardiovascular system using NMR

The current status and suggestions of the future potential for nuclear magnetic resonance imaging of the cardiovascular system are described. With many of the potential applications, there is overlap with existing methods. For example, imaging of the left ventricle can be accomplished with either echocardiography or radionuclide techniques with adequate evaluation of the left ventricular function. At current costs these conventional techniques may provide a more cost-effective approach for morphologic and functional assessment of the cardiovascular system. For this type of imaging, the advantages of NMR include its excellent resolution, the inherent tissue contrast, the sensitivity to blood motion, the 3-dimensional measure, and the lack of ionizing radiation. Because of these, NMR could provide an important adjunct for evaluation of the cardiovascular system. However for NMR to achieve its full promise as a cardiovascular imaging technique, some of its unique potentials need to be developed. These include: the ability to reliably image at least the proximal coronary arteries, the ability to delineate regional myocardial blood flow distribution, the ability to evaluate regional metabolic activity such as high-energy phosphate metabolites, and the ability to characterize myocardial disease using proton T1 and T2 alterations.

3H-2-deoxyglucose uptake after electrical stimulation of cardioactive sites in anterior medial cortex in rabbits

The anterior medial cortex is an important integrative area for cardiovascular adjustments occurring during learning and conditioning. The autoradiographic 3H-2-deoxyglucose ( 3H-2DG) method for regional cerebral metabolic activity was used to identify other forebrain regions associated with cardiovascular adjustments elicited by electrical stimulation of anterior medial cortex. Rabbits that received anterior midline stimulation that produced bradycardia and depressor responses showed increased metabolic activity in the ipsilateral mediodorsal (MD) nucleus of the thalamus and the dorsal aspect of the claustrum. Two additional animals with anterior cortical placements in the infralimbic and anterior limbic areas showed ipsilateral increased activity in perirhinal cortex, but more dorsolateral placements in the precentral agranular area did not produce increased perirhinal activity. Control animals did not show this pattern of activity. These data suggest that MD and claustrum participate in a neural circuit which mediates cardiovascular adjustments similar to those elicited by Pavlovian conditioning contingencies.

Regional Metabolic Activity in the Rat Brain During Sleep-Wake Activity

[14C]2-Deoxyglucose autoradiography was used to demonstrate regional metabolic activity in the rat brain during wake, slow-wave sleep (SWS), and REM sleep. Data are expressed as values of relative metabolic activity (RMA, regional optic density/mean brain optic density), which show the level of metabolic activity in a region, relative to the mean level of the brain. Regions exhibiting obviously decreased RMA during SWS include the cerebellum, cortical layer IV, and most of the thalamus, including the massa intermedia and lateral geniculate nuclei. Low levels of RMA in sensory relay regions during SWS reflect functional deafference of the brain. In contrast, some limbic regions, including the hypothalamic core and hippocampal dentate fascia, exhibit increased RMA during SWS. Regions exhibiting increased RMA may have functions which are carried on at high levels during sleep. The metabolic appearance of the brain in REM is very different from that in SWS. The reticular core, substantia nigra, hippocampal dentate fascia, and stratum moleculare, and many regions associated with the extrapyramidal motor system, exhibit increased RMA. The cerebellum and ventral thalamic nucleus show decreased RMA, while the lateral thalamic nuclei and cortical layer IV show no metabolic state dependency. In sum, SWS is associated with a general decrease in RMA of sensory and motor areas, and with increased RMA in some limbic regions. RMA is similar in cerebellar and hippocampal regions during REM and SWS. In contrast, RMA in many sensory relay regions does not decrease during REM, and there is REM-specific increase of RMA in some pontomesencephalic regions associated with motor function.

I-123 Labeled Radiotracers in Cardiovascular Nuclear Medicine

Radiohalogens (particularly 18F, 34mCl, 77Br, 75Br, 123I, 125I and 211At) produced in a cyclotron are nuclides of choice for radiopharmaceuticals. It has long been recognized that I-123 is the most desirable radioisotope of iodine for in vivo applications. I-123 labeled substrates suitable for imaging the myocardium include receptor binding agents, muscarinic antagonists and analogs of fatty acids. Radioiodinated (I-123) fatty acid analogs have gained significiant attention because of the possibility that these might give quantitative information regarding the regional myocardial metabolic activity by noninvasive scintigraphic methods. Incorporation of tellurium hetero into a carbon skeleton or beta methylation of a long chain phenyl fatty acid tends to prolong the retention of radioactivity in the myocardium of experimental animals. It is recognized that the radioiodine needs to be placed on a phenyl ring attached (in the ?-position) to a long chain fatty acid for the in vivo stabilityof the C-I-bond. Among the methods of radioiodination of ?-phenyl fatty acids, a method developed in our laboratory using an organo-thallium intermediate has been found to be simple, efficient, reproducible, and suitable for routine application.

Aspects of blood-brain barrier in clinical brain imaging.

The blood-brain barrier (BBB) is selectively permeable and shows a wide range of permeability to various substances in health and becomes generally permeable to all small molecules in almost all disease states. The capillary bed in brain (the BBB) is uniquely impermeable to many polar substances. The mechanism by which the capillary bed is maintained in this state is unknown, but may be an astrocytic function. In most major neuropathology, the BBB is lost because these unique structural features creating the BBB come to resemble the permeable capillaries in other tissues. Early isotopic brain scans using polar isotopes such as 99m-TcO4 depend upon this increased permeability to demonstrate focal lesions. Positron emission tomography has made it possible to label interesting biochemical substrates allowing the tracing of certain aspects of regional brain metabolic activity. The equipment required is very expensive, but single photon tomography using lipophilic tracers is much less expensive and provides tomographic representation of regional blood flow. To penetrate a healthy BBB requires that radiotracers either be lipid soluble or have an affinity for one of the selective BBB transport systems.

The effects of the GABAergic agonist muscimol upon the relationship between local cerebral blood flow and glucose utilization

The relationship between cerebral blood flow and glucose utilization was studied in conscious rats using the [ 14C]iodoantipyrine and [ 14C]2-deoxyglucose quantitative autoradiographic techniques respectively. Both blood flow and glucose use decreased in parallel in the 38 areas of the brain analyzed following administration of the GABA agonist muscimol, thus maintaining the relationship observed in control rats. The present study offers no evidence for a direct vasodilatatory action for muscimol in the conscious rat, but points to underlying regional metabolic activity as the primary determinant of cerebral blood flow.

Harmaline-induced tremor. I. Regional metabolic activity as revealed by [14C]2-deoxyglucose in cat.

Changes of local cerebral glucose consumption under the effect of tremogenic doses of harmaline were studied. To find the brain structures activated by the drug, the autoradiographic method using [14C]2-deoxyglucose was applied to young cats. After administration of harmaline, the animals were paralized with flaxedil. Results were compared to a group of control animals not injected with the drug, but submitted to the same experimental protocol. Increases of neuronal activity were observed in several structures. A) Among the relays of the olivo-cerebello-fastigio (and vestibulo)-reticulo-spinal circuit that had been claimed to fire at the frequency of the tremor, labeling was found in: 1. selected portions of the inferior olive including the medial accessory olive and the caudolateral part of the dorsal accessory olive; 2. the molecular layers of the cerebellar cortex including vermian and paravermian zones. Labeling of the olivo-cerbellar system was therefore larger than the compartment controlling the fastigial nucleus and extended to that controlling the interpositus nucleus. B) Other structures not under the direct control of the olivo-cerebellar system displayed increased radioactivity under harmaline: lateral reticular nucleus, nucleus reticularis tegmenti pontis, red nucleus and basal ganglia. Part of the nucleus ambiguus, intensely labeled in the control animals, showed decreased radioactivity under harmaline. The experiments were repeated with the same protocol in another group of animals with unilateral sections of the inferior cerebellar peduncle in order to distinguish between a direct pharmacological influence and a nervous one. Marking of the basal ganglia was not affected by pedunculotomy, suggesting a direct "pharmacological" action of the drug in this cases. On the other hand, marking of the other labeled structures was asymmetric or suppressed by pedunculotomy, and therefore could result from a "nervous" effect secondary to activation of the inferior olive.

Brain functional activity during PAG stimulation-produced analgesia: A 2-DG study

The autoradiographic 2-deoxyglucose method for regional cerebral metabolic activity was modified for use with tritium label to determine which brain stem and spinal cord nuclei changed their functional neural activity during periaqueductal gray stimulation-produced analgesia. The greatest changes in activity during electrical stimulation of the periaqueductal gray occurred in nucleus paragigantocellularis, the ventral portion of the nucleus reticularis gigantocellularis, and the nucleus cuneiformis. Substantial increases in metabolic activity were also evident in the spinal trigeminal nucleus and the substantia gelatinosa. Many of the regions which displayed increased functional activity in the present study have been shown to possess substantial enkephalin immunoreactivity. While several of these structures have previously been implicated in modulation of nociceptive transmission, this study raises the possibility that other brain stem nuclei may also participate in analgesic mechanisms.

Correlation Between Regional Cerebral Blood Flow and Oxidative Metabolism

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.

Stress distribution in lungs: a model of pulmonary elasticity.

MEAD, JERE, TAMOTSU TAKISHIMA, AND DAVID LEITH. Stress distribution in lungs: a model of pulmonary elasticity. J. Appl. Physiol. 28(5) : 596-608. 1970.Although lungs are exposed to transpulmonary pressure, the air spaces within are distended solely by forces applied from surrounding tissues. By relating these forces to the areas on which they operate, we derive the effective pressure distending air spaces. In uniformly expanded lungs this pressure probably approximates transpulmonary pressure. In nonuniformly expanded lungs the effective distending pressure differs from transpulmonary pressure, and in the appropriate sign to reduce the nonuniformity. This interdependence of air-space distention bears on a number of aspects of pulmonary function, including the size of air spaces which may be expanded from the gas-free state, the static and dynamic stability of air spaces, the dryness of air spaces, the forces distending airways and blood vessels within lungs, and the distribution of pulmonary edema. The principal function of the mechanical interdependence would appear to be to support uniform expansion of air spaces. The principal functional risk that it entails is increase in capillary transmural pressure in regions which become subjected to abnormally high outward-acting stress.