Oxygen extraction in the aging brain.
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Adult↗
Biomedical subjects
R S Frackowiak
Publications and source records attributed to R S Frackowiak.
In vivo disturbance of the oxidative metabolism of glucose in human cerebral gliomas.
Abnormalities in the oxidative metabolism of glucose in human cerebral gliomas have been studied in seven patients using positron emission tomography. Measurements of regional cerebral blood flow and oxygen consumption were obtained using the oxygen-15 steady-state inhalation technique. Values of regional cerebral glucose consumption were obtained using fluorine 18-labeled 2-fluoro-2-deoxy-D-glucose and a simplification of the method of Sokoloff. Functional values were obtained for regions of tumor and brain tissue in the middle cerebral artery territory of the contralateral cortex. Values of regional glucose consumption were calculated for both regions using a value of the lumped constant quoted for normal brain tissue (0.42). Tumor regional cerebral blood flow was comparable to that in the contralateral cortex, whereas regional cerebral oxygen consumption was depressed. This depression resulted in low tumor values of the fractional oxygen extraction ratio (0.21 +/- 0.07), indicating that oxygen supply exceeded the metabolic demand. In contrast, tumor regional cerebral glucose consumption was not depressed and regional glucose extraction ratios were similar for tumor and brain tissue. The metabolic uncoupling between regional oxygen consumption and regional glucose consumption (CMRO2/CMRGlu = 0.24 +/- 0.07 ml of oxygen per milligram of glucose) is indicative of increased aerobic glycolysis.
Adult↗
Disturbance of oxidative metabolism of glucose in recent human cerebral infarcts.
Eight patients with recent cerebral hemispheric infarction were studied with positron emission tomography and the oxygen-15 steady-state inhalation and [18F]deoxyglucose techniques to obtain values of regional cerebral blood flow, oxygen consumption, and glucose metabolism. The Sokoloff equation, used to calculate glucose metabolism, was simplified to exclude the exponential terms containing the rate constants. A value of the lumped constant quoted for normal brain (0.42) was used for infarcted regions and contralateral hemisphere. Mean regional cerebral blood flow, oxygen consumption, and glucose metabolism were all significantly depressed within the infarcts compared with the mirror regions in the contralateral cerebral hemisphere. The mean fractional extraction of oxygen was low, indicating an adequate supply of oxygen for residual oxidative metabolism. Regional oxygen consumption and glucose metabolism were significantly correlated within the infarcts, but with a relationship of 2 moles of oxygen per mole of glucose--one-third that in the contralateral hemisphere and in normal brain. Although these results suggest that the metabolizing tissue of a recent cerebral infarct utilizes aerobic glycolysis, caution about the validity of this pathophysiological observation is dictated by limitations in current positron emission tomographic tracer methodology.
Adult↗
Correction for the presence of intravascular oxygen-15 in the steady-state technique for measuring regional oxygen extraction ratio in the brain: 2. Results in normal subjects and brain tumour and stroke patients.
Values of regional cerebral oxygen extraction ratio and oxygen utilisation obtained with the oxygen-15 steady-state inhalation technique have been found to be overestimated due to the signal from intravascular oxygen-15. A previously described method to correct for this intravascular component has been applied to a series of studies on normal subjects, and on brain tumour and stroke patients. With this correction the regional cerebral oxygen extraction ratio in normals becomes comparable to the global values previously reported with arteriovenous sampling techniques. Within the lesions of brain tumour and stroke patients, the corrections have been found to be variable and often substantial. It is concluded that failure to apply this correction may result in major errors in the values for regional oxygen extraction ratio and oxygen utilisation. This is especially true when the regional blood flow and oxygen extraction ratio of a tissue is low and regional blood volume is high.
Blood Volume↗
Serial observations on the pathophysiology of acute stroke. The transition from ischaemia to infarction as reflected in regional oxygen extraction.
Regional cerebral blood flow, fractional oxygen extraction and oxygen metabolism have been measured in 34 patients after acute nonhaemorrhagic cerebral hemispheric infarction. Nine cases showed elevated oxygen extraction in the region of the early infarct, and these were the patients studied earliest after the onset of stroke. The results of serial studies to follow the evolution of the pathophysiology of acute stroke in these 9 patients are presented. The elevated oxygen extraction within the early infarct showed a significant reduction over the week following the onset of stroke. The reason for this fall in the fractional use of available oxygen varied in individual cases, and at the extremes was associated with a marked reduction in oxygen metabolism with a further small fall in residual blood flow, or a return of flow without recovery of oxygen metabolism. The significance of oxygen extraction in terms of potential viability of the tissue is discussed. The finding of a lower oxygen extraction in subcortical grey and white matter compared to cortex within the first hours or days of a major stroke is considered indicative of an earlier change from ischaemia to infarction in the deep tissues, probably related to the anatomy of the microvasculature. The interpretation of the results in the light of knowledge accumulated from studies of ischaemia in animals is presented, and problems imposed on data analysis by current limitations in positron emission tomography are discussed.
Adult↗
Late onset post-traumatic hypothalamic hypothermia.
A case of post-traumatic hypothalamic hypothermia is described. An unusually selective defect in thermoregulatory function was demonstrated together with a defect in thyroid function suggestive of impaired hypothalamic control.
Body Temperature Regulation↗
An interictal study of partial epilepsy using positron emission tomography and the oxygen - 15 inhalation technique.
Data from ten patients with complex partial seizures who underwent positron emission tomography using the 15-0 inhalation technique are presented. Decreased flow and metabolism are noted in the hemisphere ipsilateral to the EEG focus, but, in patients with unilateral foci, bilateral changes in temporal cortex are detected. Other areas maximally affected include the basal ganglia, and the cerebellum. The possible role of anticonvulsant drugs in these findings is discussed.
Adult↗
Positron tomography in ischemic cerebrovascular disease.
The authors briefly review the advances in the field of cerebrovascular disease because of PT and show that considerable insight into the pathophysiology of acute ischemic infarction is being obtained in humans.
Cerebellar Diseases↗
Cerebral energy relationships in dementia: a prospective study with positron emission tomography.
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Brain↗
Measurement of regional cerebral blood flow, oxygen extraction ratio and oxygen utilization in stroke patients using positron emission tomography.
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Brain↗
Measurement of regional cerebral blood flow and oxygen utilisation in patients with cerebral tumours using 15O and positron emission tomography: analytical techniques and preliminary results.
Regional cerebral blood flow and oxygen utilisation have been studied in 8 patients with brain tumours using continuous inhalation of C15O2 and 15O2 and positron emission tomography. The methods used to analyse the regional cerebral pathophysiology are presented. A relative uncoupling between oxygen consumption and blood flow was observed in all tumours as indicated by a decreased regional fractional extraction of oxygen (rOER). This suggest that a major proportion of these tumours had sufficient blood supply to meet oxygen metabolic demand. A decrease of blood flow in grey matter was found both in the affected and contralateral hemispheres of the brain. Matched reductions of flow and oxygen utilisation were observed in oedematous tissue.
Aged↗
Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction.
Fifteen patients with acute cerebral hemispheric infarcts have been studied with positron emission tomography and the oxygen-15 steady-state inhalation technique. Thirteen follow-up studies were also performed. The values of cerebral oxygen metabolism (CMRO2), cerebral blood flow (CBF), and oxygen extraction ration (OER) have been calculated for the infarcted regions, their borders, the symmetrical regions in contralateral cerebral hemispheres, and the cerebellar hemispheres. This study demonstrates that in the completed stroke there are thresholds for regional CMRO2 and regional CBF below which the general clinical outcome of the patients is usually poor. The ischaemic lesions invariably produce an uncoupling between the greatly decreased metabolic demand and the less affected blood supply, with very frequent instances of relative hyperperfusion. Remote effects of the hemispheric infarcts have been demonstrated, such as crossed cerebellar diaschisis and contralateral transhemispheric depression. The level of consciousness correlates with oxygen uptake and blood flow both in the posterior fossa and in the contralateral cerebral hemispheres. The follow-up studies of individual patients underline the high variability of metabolism-to-flow balance during the acute phase of the illness, and stress the need for more studies focused on repeated assessments of homogeneous patient populations.
Aged↗
A statistical study of the steady state technique for measuring regional cerebral blood flow and oxygen utilisation using 15O.
Regional cerebral blood flow and oxygen utilisation can be measured using positron emission tomography and the continuous inhalation of 15O-labelled carbon dioxide and molecular oxygen. However, there is concern about the propagation of errors in this technique. This arises from statistical uncertainties, inherent in the transmission and emission scans, being amplified in the steady state model used for calculating the physiological parameters. The magnitude of this effect has been studied using a series of repeat transmission and emission phantom measurements in which pixel count densities equivalent to those seen in the clinical data were recorded. These measurements have been used to determine the final propagated errors that occur in the calculated values of regional cerebral blood flow, oxygen extraction fraction, and oxygen utilisation rate.
Brain↗
Re: compartmental analysis of the steady-state distribution of 15O2 in the total body.
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Body Fluid Compartments↗
Measurement of CBF and CMRO2 using the continuous inhalation of C15O2 and 15O. Experimental validation using CO2 reactivity in the anaesthetised dog.
Experimental support for the steady state 15O inhalation technique, as used to measure cerebral blood flow (CBF) and oxygen utilisation (CMRO2), was obtained by describing the response of the cerebral vasculature to variations in arterial PCO2 in 6 anaesthetised dogs. Measurements were made using a positron emission tomography (ECAT II) and arterial blood sampling, during the sequential constant inhalation of C15O2 and 15O2. Values of CBF and CMRO2 were calculated for a mixture of white and grey matter, using the steady state tracer equations derived by Jones et al. (1976). The mean CMRO2 was 3.58 +/- 0.81 ml O2 . 100 ml-1 . min-1, whilst the mean CBF and OER (oxygen extraction ratio) values (for an arterial PCO2 of 40 mm Hg) were 39.9 ml . 100 ml-1 and 0.50 +/- 0.06, respectively. Arterial PCO2 was varied between 20 and 150 mm Hg. CBF was found to correlate closely with arterial PCO2, resulting in a mean slope (specific reactivity) of 1.52 +/- 0.38 ml . 10 ml-1. mm Hg-1. Pooling the flow data resulted in a linear relationship between CBF (% change) and arterial PCO2 in the range 20-70 mm Hg, with a slope (% reactivity) of 3.2% mm Hg-1 (2 P less than 0.001). The oxygen extraction ratio (OER) fell with increasing values of arterial PCO2 resulting in a stable CMRO2 throughout each study. There was no correlation between CMRO2 and artificially increased CBF. These results support and give confidence in the use of the 15O inhalation technique for measuring CBF, OER and CMRO2.
Animals↗
Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with oxygen-15 and positron tomography.
The cerebral blood flow, oxygen extraction and oxygen utilization has been measured regionally in 22 dements, and 14 aged normal volunteers. Ten demented patients were studied twice at a six-month interval from initial measurements. The use of a steady-state 15O technique and positron tomography for measuring regional cerebral blood flow, regional oxygen extraction fraction and mean cerebral oxygen utilization is discussed. The limitations of measurements are reviewed in the light of the present results and the current state of technological development in positron emission tomography is discussed. A decline in cerebral blood flow and mean cerebral oxygen utilization was correlated with increasing severity of dementia in both degenerative and vascular dements. The decline was coupled, both for the cerebral hemisphere as a whole and regionally. There was no increase in oxygen extraction ratio globally, and therefore no evidence to support the existence of a chronic ischaemic brain syndrome. Focal abnormalities in oxygen utilization were observed for both vascular and degenerative groups. In the vascular group, parietal defects were the most pronounced. Individual derangements of the regional pattern varied, reflecting the different unique patterns of ischaemic damage in these patients. In the degenerative group, parietal and temporal defects were seen in the less severe group, but a profound depression in the frontal regions with relative sparing of occipital area characterized the severe degenerative dements.
Aged↗
A theoretical study of the steady-state model for measuring regional cerebral blood flow and oxygen utilisation using oxygen-15.
There is a growing interest in the tomographic measurement of regional cerebral blood flow and oxygen utilisation using continuous inhalation of C15O2 and 15O2. This paper examines the influence of certain assumptions in the underlying steady-state model. Estimations are made for possible errors in the actual measurement of these quantities in grey and white matter.
Blood Flow Velocity↗
CMRO2 and CBF by the oxygen-15 inhalation technique. Results in normal volunteers and cerebrovascular patients.
The oxygen-15 inhalation technique has been applied to the quantitation of regional CBF, CMRO2 and OER with positron emission tomography. The introduction of corrections for gamma-ray attenuation, and for recirculation, has allowed us to obtain values for CBF, CMRO2 and OER in close agreement with values obtained using other techniques. In 27 normal volunteers mean CMRO2 shows values ranging from 4.98 to 3.79 ml/100/min, depending on the region evaluated. Mean CBF values range from 55.3 to 38.8 ml/100ml/min. Mean OER is more constant, ranging from 0.56 to 0.49, with a mean of 0.53 +/- 0.04, thus reflecting the close matching between metabolism and blood supply. We have further identified corrections for cerebral blood volume, which is measurable, and for water partition coefficient, which remains uncertain. In preliminary studies these corrections decrease the OER over the physiological range of flow by 10%, with a 15% lower CMRO2. The reproducibility of the results and the effects of aging have been studied. A series of 27 studies on acute ischaemic CVD are reported. The course of the clinical condition has been correlated with the quantitation of oxygen utilization and blood flow performed at different intervals from the onset of symptoms.
Adult↗