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Biomedical subjects

T Greitz

Publications and source records attributed to T Greitz.

At least 37 records · Page 2Linked to original sources

Regional brain glucose metabolism in drug free schizophrenic patients and clinical correlates.

Regional brain glucose metabolism was investigated in healthy volunteers (n = 10) and in drug free schizophrenic patients (n = 20). The metabolism was determined by positron emission tomography (PET) with 11C-glucose as the tracer. Diagnosis of schizophrenia was made according to RDC and DSM III. Eight patients had their first psychotic episode, four patients had a subchronic course and eight patients had a chronic course with an exacerbation of their illness. Computed tomography (CT) of the brain were made in all the subjects. Regions of interest (n = 35) were drawn on displayed CT images and the marked regions were transferred to the corresponding slice of the PET examination. The PET investigation was made in a dimly lit, quiet room with the eyes of the subject covered. The time course of the 11C-glucose uptake was measured by a four ring PET scanner (PC-384-7B). Metabolic rates of glucose varied greatly among the schizophrenic patients investigated. The variance was significantly greater than that of the controls in most regions. Decreases in mean levels of metabolic rates were related to patients with subchronic or chronic courses. Changes in metabolism were not related to previous duration of neuroleptic treatment of the patients. Left-right asymmetries were found in the temporal lobe (area 22) and the basal frontal cortex (area 11), the metabolic rates of the patients being lower on the left side compared to the controls. Asymmetry of the metabolic rate of the amygdala in hebephrenic patients was the opposite of that found in paranoid patients and controls. Negative correlations between regional metabolic rates and autistic or negative symptoms were found. Thus, the lower the metabolic rate was, the more autistic the patient. Metabolic rates were not correlated to atrophic changes of the brain. No basis for a specific alteration in frontal cortical metabolism of schizophrenics was obtained. Changes in regional metabolic rates in schizophrenia are suggested to reflect disturbances in more general mechanisms which are of importance in neuronal function.

Adult

Altered relationships between metabolic rates of glucose in brain regions of schizophrenic patients.

Regional brain glucose metabolism was studied with positron emission tomography (PET) in healthy volunteers (n = 9) and schizophrenic patients (n = 15). The patients were in an acute phase of the disease and drug free. Cerebral metabolic rate with 11C-glucose as the tracer (CMRgl) was determined in both cortical and subcortical structures. In the healthy volunteers significant correlations were found between metabolic rates of some regions, but no relationships were found between CMRgl of limbic cortical areas and that of neocortical or subcortical structures. In the patients, high and significant positive correlations were found between metabolic rates in the neocortical areas, the limbic cortical areas and the subcortical areas. The results indicate differences in the neuronal interplay between regions of healthy and schizophrenic subjects. It is proposed that neuronal systems guiding the specificity and diversity in neuronal functions between different brain regions, are abnormal in schizophrenic patients. Such a disturbance may be the basis for the diversity of psychiatric symptoms in schizophrenics.

Adult

A method of stereotaxic localization adopted for conventional and digital radiography.

A method for the determination of stereotaxic coordinates in radiography, e.g. angiography, pneumoencephalography or digital vascular radiography, is described. A special localization frame containing radiopaque structures and scales defines a diagnostic coordinate system. This frame is fixed to the X-ray-table prior to the radiographic procedure and two projections are obtained at arbitrary angles to each other. The focus-film distances do not how to be fixed. The target coordinates are then determined either by a simple graphical procedure or with the use of a digitizing x-y-table, by a computer. With the computer method the films are placed on the digitizing table and the target and a few reference points are marked using a cursor. From the relative positions the computer calculates the coordinates. With the special head fixation system, coordinates of structures visualized in radiographic examinations can be transferred to various therapeutic or diagnostic stereotaxic devices.

Angiography

Regional cerebral glucose metabolism in anxiety disorders studied with positron emission tomography before and after psychosurgical intervention. A preliminary report.

Regional cerebral metabolic rate of glucose (rCMRGl) was studied with positron emission tomography in patients suffering from severe anxiety disorders undergoing capsulotomy, an anti-anxiety psychosurgical intervention in which fronto-limbic connections are interrupted. Preliminary observations on five patients show a statistically significant reduction in rCMRGl postoperatively in the orbitomedial frontal cortex, a region knonw to be of relevance for the capsulotomy effects. Clinically, 4 of 5 patients improved after surgery. The study may provide new information on the pathophysiology of anxiety.

Adult

Applications of a computerized adjustable brain atlas in positron emission tomography.

A computerized brain atlas, adjustable to the patient's anatomy, has been developed. It is primarily intended for use in positron emission tomography (PET), but may also be employed in other fields utilizing neuro-imaging, such as stereotactic surgery. The atlas is based on anatomic information obtained from digitized cryosectioned cadaver brains. It can be adjusted to fit a wide range of individual brains with reasonable accuracy. The corresponding transformation is chosen so that the modified atlas agrees with a set of CT or MR images of the patient. The computerized atlas can be used to facilitate and improve the quantification and evaluation of PET data by: enabling the merging and comparison of results from different individuals or groups of individuals; serving as a vehicle in the comparison of different examinations of the same patient, thus reducing the need of reproducible fixation systems; supplying external information to be used in the image reconstruction, such as proper three-dimensional regions of interest; improving the attenuation and scatter corrections; helping to select suitable patient orientation during the PET study. By applying the inverse atlas transformation to the PET data volume it is possible to relate the PET information to the anatomy of the reference atlas. Reformatted PET data from different patients can thus be averaged, and averages from different categories of patients can be compared. The method will facilitate the identification of statistically significant differences in the PET information from different groups of patients.

Brain

Method for quantification of low flow velocities by magnetic resonance phase imaging.

The aim of this study was to compare the influence of flow in the velocity range 0 to 25 mm/s on modulus, phase, real and imaginary images obtained with a standard magnetic resonance scanner (Siemens Magnetom, 0.5 T), and to develop a simple method for determination of flow velocities in vivo from this information. Using a flow phantom, the flow dependent magnetic resonance imaging (MRI) signal has been studied as a function of flow perpendicular to the image slice with non-doped water (simulating moving cerebrospinal fluid) as well as with water doped with Mn2+ (simulating moving blood) for each of the four mentioned image types. The results show a marked flow dependence on all types of images studied. The variation of the signal with flow in the modulus images is relaxation-time dependent in the studied velocity range and it is non-monotone for non-doped water. In the phase images, however, the variations are monotone and not dependent on relaxation times. In modulus images the curve shape is relatively independent on flow direction, while phase images are clearly dependent on flow direction in the studied velocity range. The signal versus velocity curves for the real and imaginary images show resemblance to those for the modulus and the phase images, respectively. It is concluded that the phase information can be used to generate a signal versus velocity calibration curve, which can be used to quantify low flow velocities in vivo.

Magnetic Resonance Imaging

11C-2-deoxy-D-glucose: synthesis and preliminary comparison with 11C-D-glucose as a tracer for cerebral energy metabolism in PET studies.

11C-2-Deoxy-D-glucose has been prepared by the reaction of 11C-hydrogen cyanide with a stable precursor, 1-deoxy-2,3:4,5-di-O-isopropylidine-1-iodo-D-arabitol, thereby avoiding the synthesis of starting material immediately prior to labeling. Fast, efficient, and reproducible solvent change from dimethyl sulfoxide to ether by flash chromatography enabled the use of diisobutylaluminium hydride in the reduction of the intermediate nitrile. Hydrolysis of the imine-aluminum complex with sulfuric acid, removal of the isopropylidine protecting groups with formic acid, and HPLC purification with an Aminex HPX-87P column yielded 11C-2-deoxy-D-glucose in an aqueous solution, sterile, pyrogen-free, and ready for use in human studies. The radiochemical yield was approximately 20% after a synthesis time of 50 min. The 11C-2-deoxy-D-glucose thus obtained is presently being compared with photosynthetically prepared 11C-D-glucose in PET studies of cerebral metabolism. A preliminary report of the regional cerebral metabolic rate of glucose obtained with the two tracers in a healthy subject with visual stimulation is presented.

Brain

Preparation of 11C-labelled Raclopride, a new potent dopamine receptor antagonist: preliminary PET studies of cerebral dopamine receptors in the monkey.

A new dopamine receptor antagonist, Raclopride (S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl)]methyl-2-hydroxy- 6-methoxybenzamide, FLA 870) (1), has been labelled using [11C]ethyl iodide for alkylation of the nitrogen of the pyrrolidine ring in the corresponding secondary amine (5). The synthesis of 5 and an efficient method for the preparation of [11C]ethyl iodide are described. The 11C-labelled FLA 870 (1) was purified by HPLC and then used in positron emission tomography to visualize the dopamine receptor-rich areas of the monkey brain. The images obtained show selective accumulation of FLA 870 in striatum and a 10-fold separation between the binding to caudate vs cerebellum.

Animals

11C-labeled 4-isopropylantipyrine: preparation and biological evaluation as a blood flow tracer in positron emission tomography (PET).

Radiolabeled 4-isopropylantipyrine (1) has been synthesized and evaluated as a tracer for the measurement of cerebral blood flow (CBF). Methylation of 4-isopropyl-3-methyl-1-phenylpyrazol-5-one (2) with [14C]methyl iodide in acetonitrile gave [14C]-1 in radiochemical yields of 10-20%. Its blood-brain partition coefficient in rats was determined to be 0.62 +/- 0.03 (mean +/- SE). Autoradiographic determination of regional cerebral blood flow under normal flow conditions indicated that [14 C]-1 gives results essentially identical with those obtained with the widely used tracer [14C]-4-iodoantipyrine ( [14C]-IAP). Studies performed in high-flow states indicated that [14C]-1 is not more diffusion limited than [14C]-IAP. A rapid synthesis was therefore developed for the preparation of [11C]-1. Radiochemical yields were increased to 40-50% when the alkylation of 2 with [11C]methyl iodide was performed in dimethyl sulfoxide using solid potassium hydroxide as a base. Since the 11C-labeled compound can easily be produced in large quantities and since the tracer is not diffusion limited at flow rates commonly observed in normal and most pathological states in man, [11C]-4-isopropylantipyrine will be used for in vivo studies of CBF using positron emission tomography.

Animals

Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography.

Two substituted benzamides, FLB 524 and raclopride, were labeled with 11C and examined for their possible use as ligands for positron emission tomography (PET)-scan studies on dopamine-2 (D-2) receptors in the brains of monkeys and healthy human subjects. Both ligands allowed the in vivo visualization of D-2 receptor binding in the corpus striatum caudate nucleus/putamen complex in PET-scan images. [11C]Raclopride showed a high ratio of specific striatal to nonspecific cerebellar binding, and the kinetics of binding of this ligand made it optimal for PET studies. The in vivo binding of [11C]raclopride in the striatum of cynomolgus monkeys was markedly reduced by displacement with haloperidol. This and previous in vitro data indicate that [11C]raclopride binds selectively to striatal D-2 dopamine receptors. In healthy human subjects, [11C]raclopride binding in the caudate nucleus/putamen was 4- to 5-fold greater than nonspecific binding in the cerebellum. In comparison with previously available ligands for PET-scan studies on central dopamine receptors in man, [11C]raclopride appears to be advantageous with regard to (i) specificity of binding to D-2 receptors, (ii) the high ratio between binding in dopamine-rich (caudate, putamen) and dopamine-poor (cerebellum) human brain regions, and (iii) rapid association and reversibility of specific binding. [11C]Raclopride should be a valuable tool for characterizing D-2 receptors in the brains of patients with neuropsychiatric disorders.

Animals

Effects of prenalterol and volume loading with dextran on haemodynamics and oxygen consumption in dogs during high epidural block with special reference to the splanchnic region.

High lumbar epidural block was induced in seven dogs, causing a fall in mean arterial blood pressure (AP) from 24.5 +/- 2.9 to 12.0 +/- 3.1 kPa owing to reductions in cardiac output (QT) and systemic vascular resistance (SVR) to 67% and 68% of the pre-epidural values. Volume loading with dextran 10 ml X kg-1 b.w. increased QT nearly to the pre-epidural value. SVR decreased further to 61% of the pre-epidural value and AP was only slightly increased to 14.9 +/- 2.7 kPa. Subsequent administration of prenalterol 20 micrograms X kg-1 b.w. caused a further increase in QT to 17% above the pre-epidural value due to an increase in heart rate of 51 beats/min. AP did not change since SVR decreased further to 49% of the pre-epidural value. The hepatic arterial blood flow (QHA) was essentially unchanged during epidural block as well as during volume loading, while the portal venous blood flow (Qpv) was changed concurrently with (QT). In spite of the decrease in SVR, the preportal and hepatic arterial vascular resistances were not diminished following prenalterol. The increase in OT must therefore have favoured other vascular beds. Hepatic and pre-portal tissue oxygen uptakes were unchanged during the experimental procedure, while whole-body oxygen uptake decreased by 20% following the epidural block and increased nearly to the pre-epidural level following volume loading in combination with prenalterol.

Animals

Effects of ephedrine on haemodynamics and oxygen consumption in the dog during high epidural block with special reference to the splanchnic region.

High lumbar epidural block was induced in seven dogs with 0.5% bupivacaine, causing a fall in mean arterial blood pressure (AP) from 19.2 +/- 3.2 to 10.5 +/- 3.2 kPa, owing to equal reductions in cardiac output (QT) and systemic vascular resistance (SVR). After the administration of ephedrine (a single injection of 200-300 micrograms X kg-1 b.w. followed by a continuous infusion of 10-20 micrograms X kg-1 b.w. X min-1) AP, QT and SVR rose to pre-epidural values. Furthermore, the hypokinetic circulation following the epidural block returned to normokinetic levels. Portal venous blood flow was increased from 16.5 +/- 6.2 to 25.5 +/- 4.3 ml X kg-1 b.w. X min-1 by ephedrine, while the hepatic arterial blood flow was unchanged and remained at its pre-epidural level. In spite of a slight rise in hepatic oxygen consumption from 1.2 +/- 0.4 to 1.6 +/- 0.6 ml X kg-1 b.w. X min-1, the percentages of oxygen extracted from the portal vein and the hepatic artery decreased significantly. It is concluded that ephedrine restores central and splanchnic haemodynamics in a desirable manner during high epidural anaesthesia.

Anesthesia, Epidural

Discrepancies in brain tumor extent as shown by computed tomography and positron emission tomography using [68Ga]EDTA, [11C]glucose, and [11C]methionine.

A patient with an anaplastic (malignant) astrocytoma was examined with computed tomography (CT) and with positron emission tomography (PET), in the latter case using [68Ga]EDTA, [11C]glucose, and [11C]methionine. The CT examination as well as the [68Ga]EDTA study showed a small tumor located in the region of the head of the left caudate nucleus. The [11C]glucose examination showed increased uptake on the same region, as did the [11C]methionine examination, but the latter also showed a considerable uptake in the entire left thalamic region. The patient died 15 days after the [11C]methionine study and a histologic evaluation of thin sections obtained at autopsy showed excellent agreement between tumor extent and activity distribution after [11C]methionine administration. The tumor tissue seen only with [11C]methionine was histologically different from that part of the tumor observed with the other tracers. Although cytologically similar, the latter showed large necrotic areas and an ability to induce marked endothelial proliferation, whereas in the former neither necroses nor notable endothelial proliferation was seen. In this case more than 50% of the tumor would have remained radiologically imperceptible without the [11C]methionine PET examination.

Astrocytoma

Haemodynamics and oxygen consumption in the dog during high epidural block with special reference to the splanchnic region.

High epidural block (Th I-IV) with bupivacaine was carried out in 16 dogs. Mean arterial blood pressure decreased to 52% of control value owing to nearly equal decreases in systemic vascular resistance and cardiac output. Portal venous blood flow decreased from 25.8 +/- 8.6 to 16.7 +/- 7.2 ml/kg b.w. X min-1 following epidural block, while hepatic arterial blood flow remained unchanged at 9.1 +/- 3.1 ml/kg b.w. X min-1 owing to a reduction in hepatic arterial resistance of 51%. Hepatic oxygen uptake was maintained during the epidural block through increased oxygen extraction. However, total oxygen uptake decreased by 18% and, in spite of this, arteriovenous oxygen content difference increased by 25%, indicating circulatory depression.

Anesthesia, Epidural

Effects of dihydroergotamine on haemodynamics and oxygen consumption in the dog during high epidural block with special reference to the splanchnic region.

Dihydroergotamine (DHE) 0.02 mg X kg-1 was administered i.v. in 9 dogs with high epidural block. Mean arterial blood pressure was restored from 11.0 +/- 2.4 kPa to 18.8 +/- 2.5 kPa by DHE due to a near twofold increase in systemic vascular resistance while cardiac output was unchanged. Hepatic arterial blood flow was reduced by 50% by a marked increase in hepatic arterial resistance above the pre-epidural value, while portal venous blood flow remained unchanged. Hepatic oxygen consumption decreased following DHE in spite of an increase in total oxygen consumption, probably partly due to a reduction in hepatic arterial oxygen availability. The mechanism by which the arterial blood pressure is restored by DHE in dogs during high epidural block must be regarded as unfavourable, especially with respect to the liver.

Anesthesia, Epidural