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Biomedical subjects

R S Frackowiak

Publications and source records attributed to R S Frackowiak.

At least 271 records · Page 15Linked to original sources
PubMed1987

Measurement of glucose utilisation with [18F]2-fluoro-2-deoxy-D-glucose: a comparison of different analytical methods.

A number of different analytical methods were applied to dynamic scans obtained with [18F]2-fluoro-2-deoxy-D-glucose and positron emission tomography. In particular, methods applying three, four, standard, or no rate constants were compared in four studies on three normal subjects. In addition, regional cerebral blood flow, oxygen utilisation, and blood volume were measured using the oxygen-15 steady-state inhalation technique. There was a large difference between values of glucose utilisation obtained with the various analytical methods, in particular between methods using three or four rate constants. This difference was not due to contamination of the tracer with [18F]2-fluoro-2-deoxy-D-mannose. For dynamic techniques, the separate measurement of regional cerebral blood volume was essential. Static techniques (single scans with standard or no rate constants) were best related to dynamic techniques utilising four rate constants. From the results, it followed, however, that these static techniques can only be applied clinically if relatively large disturbances of glucose metabolism and no changes in rate constants are anticipated. The lumped constant was assessed from the combined measurement of oxygen and glucose utilisation and was higher than previously reported.

Deoxy Sugars↗
PubMed1987

Acute cerebral ischaemia: concurrent changes in cerebral blood flow, energy metabolites, pH, and lactate measured with hydrogen clearance and 31P and 1H nuclear magnetic resonance spectroscopy. I. Methodology.

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. This has been correlated with changes in local pH, tissue lactate, and phosphorus energy metabolites measured in the same animals with 1H and 31P nuclear magnetic resonance (NMR) spectroscopy. The NMR measurements were made with two surface coils, one on each hemisphere. This article describes the experimental details and shows that in acute unilateral or bilateral forebrain ischaemia metabolic changes can be monitored by NMR with no significant interhemispheric cross talk. The metabolic effects of reperfusion are also shown. The model allows the definition of the time course of the metabolic consequences of regional ischaemia and reperfusion in individual laboratory animals.

Acute Disease↗
PubMed1987

Acute cerebral ischaemia: concurrent changes in cerebral blood flow, energy metabolites, pH, and lactate measured with hydrogen clearance and 31P and 1H nuclear magnetic resonance spectroscopy. II. Changes during ischaemia.

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anesthesia. This has been correlated with changes in local pH, tissue lactate, and phosphorus energy metabolites measured in the same animals with 1H and 31P nuclear magnetic resonance spectroscopy. We demonstrate a threshold flow value for the metabolic changes associated with energy failure at a level similar to the values previously reported for electrical failure and tissue water accumulation, but higher than that associated with breakdown of extracellular potassium homeostasis.

Animals↗
PubMed1987

Regional brain hematocrit in stroke by single photon emission computed tomography imaging.

Nineteen studies on 18 subjects were performed by single photon emission computed tomography (SPECT) of the head after the successive intravenous administration of a plasma label (99mTc-human serum albumin [HSA]) and 99mTc-labeled autologous red blood cells (RBC). Two sets of cerebral tomographic sections were generated: for cerebral 99mTc-HSA alone and for combined 99mTc-HSA and 99mTc-RBC. By relating counts in regions of interest from the cerebral tomograms to counts from blood samples obtained during each tomographic acquisition, regional cerebral haematocrit (Hct) was calculated by the application of a simple formula. Results show 1) lower cerebral Hct than venous Hct (ratio of HCT brain/Hct venous 0.65-0.90) in all subjects, and 2) comparison between right and left hemisphere Hct in 3/3 normal subjects, 6/6 patients with transient ischaemic attacks and 3/8 patients with stroke showed no significant difference. However, in 3/8 patients with stroke (most recent strokes) significant differences were found, the higher Hct value corresponding to the affected side.

Adult↗
PubMed1986

Inhibition of L-[18F]fluorodopa uptake into human brain by amino acids demonstrated by positron emission tomography.

The brain uptake of L-[18F]fluorodopa was measured by positron emission tomography in a healthy male volunteer both under fasting conditions and during intravenous amino acid loading. A significant reduction of tracer uptake into the brain was demonstrated with amino acid loading. This finding represents the first direct evidence for competition between L-dopa and other amino acids for uptake across the blood-brain barrier obtained in vivo in a human subject. It underlines the possible importance of interference by dietary amino acids with the therapeutic actions of L-dopa in Parkinson's disease.

Adult↗
PubMed1986

Ipsilateral blepharospasm and contralateral hemidystonia and parkinsonism in a patient with a unilateral rostral brainstem-thalamic lesion: structural and functional abnormalities studied with CT, MRI, and PET scanning.

A patient developed progressive right hemidystonia in childhood. Subsequently, left-sided blepharospasm, slurred and stuttering speech, and right-sided rigidity and bradykinesia, responsive to dopamine agonists, appeared. Investigation with computed tomography and magnetic resonance imaging (MRI) at age 43 years revealed a left-sided calcified rostral brainstem-thalamic lesion of uncertain aetiology. Although no structural lesion was seen in the striatal regions, L-[18F]-fluorodopa uptake was severely diminished in the left striatum but normal on the right. Dopamine receptor binding identified by [11C]-methylspiperone was in the normal range on both sides.

Adult↗
PubMed1986

Brain energy metabolism and dopaminergic function in Huntington's disease measured in vivo using positron emission tomography.

A 48-year-old man with typical Huntington's disease was investigated with computed tomography (CT) and positron emission tomography. Regional cerebral blood flow, oxygen extraction, oxygen and glucose utilisation, L-Dopa uptake, and dopamine (D2) receptor binding were measured using several positron-labelled tracers. CT showed slight atrophy of the head of caudate but no cortical atrophy, although distinct frontal lobe dysfunction was present on psychometric testing. Oxygen and glucose metabolism and cerebral blood flow were decreased in the striata and to a lesser extent in frontal cortex. Cerebral blood flow was in the low normal range throughout the remainder of the brain. A normal metabolic ratio was found in all regions, since the changes in glucose utilisation paralleled those in oxygen consumption. The capacity of the striatum to store dopamine as assessed by L-[18F]-fluorodopa uptake was normal, but dopamine (D2) receptor binding was decreased when compared to normal subjects.

Carbon Radioisotopes↗
PubMed1986

Glucose transport across the blood-brain barrier in normal human subjects and patients with cerebral tumours studied using [11C]3-O-methyl-D-glucose and positron emission tomography.

The kinetics of the regional cerebral uptake of [11C]3-O-methyl-D-glucose ([11C]MeG), a competitive inhibitor of D-glucose transport, have been studied in normal human subjects and patients with cerebral tumours using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and blood flow enabled corrections for the contribution of intravascular tracer signal in PET scans to be carried out and regional unidirectional cerebral [11C]MeG extractions to be determined. A three-compartment model containing an arterial plasma and two cerebral compartments was required to produce satisfactory fits to experimental regional cerebral [11C]MeG uptake data. Under fasting, resting conditions, normal controls had mean unidirectional whole-brain, cortical, and white matter [11C]MeG extractions of 14, 13, and 17%, respectively. Mean values of k1 and k2, first-order rate constants describing forward and back transport, respectively, of tracer into the first cerebral compartment, were similar for [11C]MeG and [18F]2-fluoro-2-deoxy-D-glucose (18FDG), a second competitive inhibitor of D-glucose transport. k3, a rate constant describing FDG phosphorylation, was 20 times higher for cortical FDG uptake than the k3 fitted for [11C]MeG cortical uptake. Glioma [11C]MeG extractions ranged from normal levels of 12% to raised levels of 30%. Transport of [11C]MeG in and out of contralateral cortical tissue was significantly depressed in patients with gliomas. It is concluded that under fasting, resting conditions, regional cerebral glucose extraction remains relatively uniform throughout normal brain tissue. Gliomas, however, may have raised levels of glucose extraction. The nature of the second cerebral compartment required to describe [11C]MeG uptake is unclear, but it could represent either a useless phosphorylation-dephosphorylation cycle or nonspecific tracer uptake by a cerebral subcompartment.

3-O-Methylglucose↗
PubMed1986

A comparison between regional cerebral blood flow measurements obtained in human subjects using 11C-methylalbumin microspheres, the C15O2 steady-state method, and positron emission tomography.

Regional cerebral blood flow (rCBF) values were measured in nine normotensive subjects with known previous myocardial infarctions using 15 mu 11C-methylalbumin microspheres and positron emission tomography (PET). Microspheres were injected directly into the left ventricle of each subject during routine cardiac angiography and blood flow calibrated using the reference sample technique. rCBF values were compared with those obtained for a group of fifteen age-matched normal controls using the C15O2 steady-state inhalation technique. Using 1 cm radius circular regions of interest, the 11C-microspheres approach yielded mean blood flow values of 51 ml/100 ml/min and 48 ml/100 ml/min for regions of interest dominated by temporal and frontal cortical grey matter respectively. An rCBF value of 32 ml/100 ml/min was obtained for regions of interest dominated by frontal white matter. Mean rCBF values obtained for these regions using the C15O2 method were not significantly different (52 ml/100 ml/min, 44 ml/100 ml/min, and 28 ml/100 ml/min respectively), but the C15O2 approach gave a significantly lower rCBF value than the 11C-microspheresfor regions of interest dominated by occipital grey matter. Although the two groups of subjects studied were not strictly equivalent, the good agreement between blood flow values obtained using the 11C-microspheres and the C15O2 techniques is of interest, and suggests that the assumptions of the C15O2 steady-state approach do not lead to large errors in practice.

Aged↗
PubMed1986

Regional cerebral blood flow and oxygen metabolism in dementia due to vascular disease.

Regional cerebral blood flow (CBF), oxygen utilisation (CMRO2) and fractional oxygen extraction (OER) were measured by positron emission tomography in patients with multi-infarct dementia. A matched reduction of both CBF and CMRO2 in the majority of patients indicated that in general, reduced cerebral perfusion in this condition is appropriate for the reduced metabolic demands of a damaged brain. Only in a very small minority of patients with dementia associated with bilateral carotid artery occlusion was CBF inappropriately low and OER raised. In these exceptional cases with critical cerebral perfusion, surgical measures to increase CBF could theoretically arrest or slow down the progress of dementia.

Brain↗
PubMed1985

Pathophysiology of human cerebral ischemia: studies with positron tomography and 15oxygen.

Patients with acute occlusion of a major cerebral artery sequentially call on a hemodynamic reserve quantifiable in terms of rCBF and rCBV and then an oxygen carriage reserve quantifiable in terms of rOER (Fig. 10). If both are exhausted, ischemia supervenes and rCMRO2 becomes linearly related to rCBF. Depending on the degree and duration of fall in rCMRO2, variable degrees of infarction occur. Infarction occurs more rapidly in subcortical than cortical tissue. The phase of maximal rOER is short, and rapid evolution by either reflow or delayed cell death results in an invariable decline of rOER to subnormal levels in the face of a low rCMRO2 (Fig. 11). This combination is characteristic of infarcted tissue. In some instances, partial infarction with a low perfusion reserve is observed with low rCMRO2, high though submaximal rOER, and no increase in rCMRO2 if rCBF is raised. This is a precarious situation predisposing to extension of infarction and suggests blood pressure should not be lowered acutely after a stroke unless the latter is caused by hypertensive encephalopathy. This pattern, however, is rare, short-lived, and usually followed by late reflow or further infarction as a further fall in rCPP occurs, transiently or permanently. Tests of rCPP and the two homeostatic mechanisms involved in maintaining rCMRO2 using non-PET techniques suggest themselves and might form an objective basis for selection of patients for prophylactic revascularization or bypass operations. PET techniques are now becoming available for assessing the blood-brain barrier, tissue pH, and amino acid metabolism, all of which may have relevance to the further understanding of the evolution of infarcts. The rapid study of very early ischemic events is now required to elucidate further the potential for cerebral salvage therapy once ischemia has occurred.

Brain↗
PubMed1985

Positron emission tomography.

Positron computed tomography allows for the in vivo measurement of the regional tissue concentration of positron-emitting radionuclides such as 15O, 11C, 13N, and 18F. By using different tracers, a variety of metabolic processes can be quantitated. These include blood flow, oxygen utilization, glucose utilization, amino acid transport, blood volume, cation exchange, pH, and others. This review will contain three sections. First, the principles of positron computed tomography and the progress in instrumentation will be discussed. Second, tracer models will be analyzed. These models are vital in the extraction of physiological data from the measurements of activity. Finally, clinical studies will be evaluated in terms of new pathophysiological information obtained.

Biomedical Engineering↗
PubMed1984

Positron emission tomographic studies in aging and cerebrovascular disease at Hammersmith hospital.

This paper attempts to place into perspective the present state of clinical investigation with PET in neurology. To this end we briefly review the work of the neurology group of the MRC Cyclotron Unit at Hammersmith Hospital, by reference to studies performed in normal subjects and in patients with cerebrovascular disease. Based on the current understanding of human physiology in health and disease as a result of this new method of clinical measurement in humans, we speculate on some possible future developments and present constraints in the application of PET to clinical research.

Acute Disease↗
PubMed1984

Positron emission tomography of the brain: new possibilities for the investigation of human cerebral pathophysiology.

In the foregoing an overview of positron emission tomography has been presented. Its theoretical, technical, and methodological implications, as well as its clinical applications have been outlined. The emphasis has been on the quantitative aspects of the method and its usefulness is investigating normal and pathological functions of brain tissue. Although the potential of this new research technique is obvious, many theoretical and practical difficulties still need to be solved. Nevertheless it provides an opportunity to bridge the gap between basic experimental research and clinical medicine.

Aging↗
PubMed1984

A method to quantitate the fractional extraction of rubidium-82 across the blood-brain barrier using positron emission tomography.

Previously, rubidium-82 and positron emission tomography (PET) have been used to assess qualitatively the integrity of the blood-brain barrier (BBB). In this report, a method is described to measure the fractional extraction of rubidium across the BBB using the constant intravenous infusion of rubidium-82. In addition, the continuous inhalation of oxygen-15-labelled carbon dioxide is needed to measure regional CBF, and it is also necessary to measure regional cerebral blood volume. The assumptions underlying the model are identified, and the impact of deviations from these assumptions is described. From radiation dose and statistical considerations, it is shown that for normal cerebral tissue and the PET scanner used in this study, the rubidium extraction fraction can be quantitated only for regions as large as a cerebral hemisphere. However, quantitation is also possible for smaller regions where the focal extraction of rubidium is increased.

Blood-Brain Barrier↗