Biomedical subjects

S Valind

Publications and source records attributed to S Valind.

At least 37 records · Page 2Linked to original sources

PubMed1998

Brain networks affected by synchronized sleep visualized by positron emission tomography.

Nineteen lightly sleep-deprived healthy volunteers were examined with H2(15)O and positron emission tomography (PET). Scanning was performed during wakefulness and after the subjects had fallen asleep. Sleep stage was graded retrospectively from electroencephalogram (EEG) recordings, and scans were divided into two groups: wakefulness or synchronized sleep. Global flow was quantified, revealing no difference between sleep and wakefulness. A pixel-by-pixel-blocked one-way analysis of variance (ANOVA) was performed after correcting for differences in anatomy and global flow. The sum of squares of the z-score distribution showed a highly significant (P < 0.00001) omnibus difference between sleep and wakefulness. The z-score images indicated decreased flow in the thalamus and the frontal and parietal association cortices and increased flow in the cerebellum during sleep. A principal component (PC) analysis was performed on data after correction for global flow and block effects, and a multivariate analysis of variance (MANOVA) on all PC scores revealed significant (P = 0.00004) differences between sleep and wakefulness. Principal component's 2 and 5 correlated to sleep and revealed distinct networks consisting of PC 2, cerebellum and frontal and parietal association cortices, and PC 5, thalamus.

Analysis of Variance↗

PubMed1997

High uptake of [2-11C]acetyl-L-carnitine into the brain: a PET study.

The brain uptake of acetylcarnitine was investigated in rhesus monkeys using different position labeled acetyl-L-carnitine and related molecules with 11C by positron emission tomography. The uptake values of radio-labeled acetylcarnitine into the brain were quite different depending on the labeling positions of 11C. That is, the uptake values of L-[methyl-11C]carnitine and acetyl-L-[methyl-11C]carnitine were almost the same and extremely low, while the uptake of [1-11C]-acetyl-L-carnitine was slightly higher. The uptake value of [2-11C]acetyl-L-carnitine was by far the highest among the 11C-labeled acetyl-L-carnitine and L-carnitine. The uptake of [2-11C]acetyl-L-carnitine into the brain was suppressed by the intravenous administration of glucose. These results suggest that endogenous serum acetyl-L-carnitine has some roles on conveying an acetyl moiety into the brain especially under an energy crisis, and that an unknown metabolic pathway of [2-11C]acetyl moiety might be rather active in the brain.

Acetylcarnitine↗

PubMed1997

No difference in cerebral glucose metabolism in patients with Alzheimer disease and differing apolipoprotein E genotypes.

BACKGROUND: Recent findings of a reduced cerebral metabolic rate of glucose (CMRGlu) in at-risk relatives of patients with Alzheimer disease (AD) who carry the apolipoprotein E (APOE) epsilon 4 allele suggest a causative role for the E4 isoform in cognitive changes that lead to AD. It is not known whether epsilon 4 allele-associated deficits exist in patients with clinical AD. OBJECTIVE: To determine whether distinct patterns of cerebral hypometabolism exist in patients who carry the epsilon 4 allele. PATIENTS AND METHODS: Information on the CMRGlu and APOE genotype was available for 46 patients at a memory disorders clinic: 31 patients were diagnosed as having probable AD, 3 demented patients did not meet criteria for AD, and 12 patients had mild memory complaints. Positron emission tomography with the use of 18F-fludeoxyglucose was used to calculate the CMRGlu in the frontal and temporoparietal regions of the cortex. Estimates were standardized to the sensorimotor area of the cortex. Linear regression models were constructed to relate the APOE genotype to the CMRGlu, adjusting for cognitive status (ie, the Mini-Mental State Examination score). RESULTS: Distinct patterns of the CMRGlu did not emerge for patients with different APOE genotypes. Bilateral deficits in the CMRGlu were found in the patients with AD. Left-right asymmetry was found in 8 of 12 patients with mild memory complaints: 7 of 8 had CMRGlu ratio less than 0.85 in the left side of the temporoparietal region of the cortex. CONCLUSIONS: The APOE epsilon 4 allele does not appear to be associated with specific deficits in brain metabolism in patients with AD despite evidence that the epsilon 4 allele is associated with preclinical alterations. This finding is consistent with previous epidemiologic results that have demonstrated a higher risk for AD in carriers of the epsilon 4 allele, but no change in the rate of progression of AD.

Adult↗

PubMed1997

Do organic solvents induce changes in the dopaminergic system? Positron emission tomography studies of occupationally exposed subjects.

OBJECTIVES: The objective of this study was to test the hypothesis that long-term occupational exposure to organic solvents may effect the levels and turnover of dopamine in man. METHODS: A study was performed on 17 patients with neuropsychiatric symptoms due to occupational solvent exposure, and 11 healthy non-exposed male volunteers (controls). Positron emission tomography (PET) was used to assess striatal dopaminergic function, using L-[11C]DOPA, [11C]nomifensine and [11C]raclopride as tracers. RESULTS: The rate of dopamine synthesis was significantly increased among subjects with occupational exposure to organic solvents compared with non-exposed controls. After controlling for the difference in age between exposed and controls, the effect of solvent exposure became less apparent and was reduced from +32% (P = 0.009) to +25% (P = 0.07). There were no differences with regard to the binding of [11C]nomifensine. Patients with and without the diagnosis of toxic encephalopathy did not differ with regard to their putaminal uptake of L-[11C]DOPA, [11C]nomifensine and [11C]raclopride. CONCLUSION: The data support the hypothesis that long-term exposure to organic solvents may increase the rate of dopamine synthesis in the brain without affecting the number of presynaptic terminals or postsynaptic dopamine receptors.

Brain↗

PubMed1997

Identification of human brain loci processing esophageal sensation using positron emission tomography.

BACKGROUND & AIMS: Brain loci that process human esophageal sensation remain unidentified. The aim of this study was to identify the brain loci that process nonpainful and painful human esophageal sensation. METHODS: In 8 healthy subjects (7 men; age range, 24-47 years), distal esophageal stimulation was performed by repeatedly inflating a balloon at volumes that produced either no sensation, definite sensation, or pain. Two positron emission tomography scans were performed for each sensation using H2(15)O. Magnetic resonance brain scans were also performed in each subject, and the positron emission tomography data were coregistered with magnetic resonance scans. Analysis of covariance-corrected t images showing the contrasts definite sensation-baseline, pain-baseline, and pain-definite sensation were created. RESULTS: Nonpainful stimulation elicited bilateral activations along the central sulcus, insular cortex, and frontal/parietal operculum (P < 0.01). Painful stimulation produced more intense activations of the same areas and additional activation of the right anterior insular cortex and the anterior cingulate gyrus. Multiple areas of decreased activation were also observed; prominent among these was the right prefrontal cortex, which was inhibited during both nonpainful and painful stimulation. CONCLUSIONS: Esophageal sensation activates bilaterally the insula, primary somatosensory cortex, and operculum. The right anterior insular cortex and anterior cingulate gyrus process esophageal pain.

Adult↗

PubMed1997

Synthesis of O-[11C]Acetyl CoA, O-[11C]Acetyl-L-carnitine, and L-[11C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey.

The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with 11C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1-11C]acetyl CoA and O-[2[11C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1-11C]acetyl-L-carnitine and O-[2-11C] acetyl-L-carnitine in 70-80% yield, based on [1-11C]acetate or [2-11C]acetate, respectively. By an N-methylation reaction with [11C]methyl iodide, L-[methyl-11C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl-11C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [11C]methyl iodide. Initial data of the kinetics of the different 11C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented.

Acetyl Coenzyme A↗

PubMed1997

Regional cerebral blood flow and oxygen metabolism during migraine with and without aura.

Eleven cases of migraine with and without aura were investigated with positron emission tomography (PET). Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO2) and oxygen extraction (rOER) were measured during baseline (n = 11), aura (n = 6), headache (n = 10) and after treatment with sumatriptan (n = 4). Data were analysed using an ROI-based approach from 26 different anatomically defined regions, and also an exploratory approach whereby all subjects were normalized to a stereotactic brain atlas; t-maps were constructed by depicting significant changes between states. The exploratory approach revealed a region corresponding to the primary visual cortex with significant reductions in rCBF (23.1%) and rCMRO2 (22.5%), but no change in rOER during the headache phase compared to baseline. These data suggest that cerebral ischemia was not the primary cause of the attacks in these cases.

Adult↗

PubMed1997

A positron emission tomography study of cerebral blood flow and oxygen metabolism in healthy male volunteers anaesthetized with eltanolone.

BACKGROUND: The effects of eltanolone anaesthesia in humans on regional cerebral blood flow, regional cerebral metabolic rate of oxygen and oxygen extraction ratio were to be evaluated using positron emission tomography (PET). METHODS: Six healthy male volunteers were studied. Series of PET-measurements with 15O and H2(15)O were carried out in the awake state (baseline)(n = 6), during eltanolone anaesthesia (n = 5) and during early recovery (n = 5), when the subjects were oriented with respect to person, place and time. Eltanolone was given as a programmed infusion. RESULTS: Cerebral blood flow (rCBF) was reduced in almost all cortex regions studied by 31 +/- 16% (mean +/- SD, P < 0.01). During recovery rCBF increased to 109 +/- 26% of pre-anaesthetic baseline levels (P < 0.01). Eltanolone in the doses administered lowered oxygen metabolism (rCMRO2) by 52 +/- 8% (P < 0.01) in cortex regions. During recovery rCMRO2 increased to 90 +/- 13% of baseline (P < 0.01). The oxygen extraction (OER) in cortical regions decreased by 32 +/- 23% (P < 0.01) during anaesthesia and returned to 82 +/- 10% of baseline (P < 0.01) during recovery. Less reduction in cortical blood flow during eltanolone anaesthesia was seen in the uncus (P < 0.01), though no differences in the depression of oxygen metabolism were seen. Oxygen extraction remained homogeneous throughout the brain. CONCLUSION: Eltanolone anaesthesia was shown to reduce cerebral oxygen metabolism and cerebral blood flow in healthy volunteers. There were no signs of ischaemic effects.

Adult↗

PubMed1997

Positron emission tomography studies of healthy volunteers--no effects on the dopamine terminals and synthesis after short-term exposure to toluene.

Despite extensive research, the mechanisms for the effects of organic solvents on the central nervous system are still unknown. One mechanism proposed is that solvents interfere with the synthesis of neurotransmitters. In the present study 11 male healthy volunteers were exposed during 15 min to 100 p.p.m. toluene at light physical exercise, and the dopamine decarboxylase activity and number of terminals in putamen were measured before and after exposure by positron emission tomography. Two different tracers were used [beta-11C]L-DOPA for decarboxylase activity during the in vivo synthesis of dopamine, and [11C]nomifensine to estimate the number of terminals. Although there was a slight increase in the rate of dopamine synthesis in the putamen after the exposure, this difference was not statistically significant (P = 0.4). No effect was observed with regard to the uptake of nomifensine. There was no significant relationship between the dose of toluene and rate of dopamine synthesis, and no significant correlation between the time from end of exposure to start of the PET-camera and DOPA. Our findings indicate that short term exposure to 100 p.p.m. of toluene does not affect the rate of dopamine synthesis or the number of presynaptic terminals.

Adult↗

PubMed1996

Acylcarnitine metabolism during fasting and after refeeding.

Carnitine metabolism during starvation and just after refeeding was studied by the measurement of acylcarnitine (ACR) and total carnitine (TCR) concentration in the serum and liver of mice. Starvation caused marked increases in the concentration of serum ACR, and of acid-soluble ACR in the liver. The refeeding caused the quick decrement of serum ACR with a concomitant marked increase in the level of acid-soluble TCR in the liver. Through the use of positron emission tomography in a rhesus monkey, a marked increase in [2-11C]acetyl-L-carnitine uptake in the liver was observed after the administration of glucose accompanying the decrease of serum ACR. From this study, it is clear that the mammalian liver can salvage and conserve the unused ACR when the state of energy metabolism is improved.

Acylation↗

PubMed1996

Activation PET scanning in pretreatment evaluation of patients with cerebral tumours or vascular lesions in or close to the sensorimotor cortex.

Treatment of tumours and vascular lesions in or close to eloquent cortex may inflict neurological deficits. Intra-operative mapping procedures have been used for many decades in efforts to minimize neurological sequelae. The possibility for non-invasive pre-operative brain mapping has emerged with the advent of positron emission tomography (PET). In this paper we report on 11 patients with a tumour or vascular lesion in or close to the sensorimotor (10 patients) or visual cortex (one patient). The patients were subjected to activation PET scanning by means of vibrotactile or visual stimulation. The results show that in most of the patients the important relation between the lesion and the sensorimotor cortex could be determined. The patient with a lesion in the occipital lobe had involvement of the entire visual cortex as judged by comparison with activated areas on the nonlesion side.

Adult↗

PubMed1996

Simultaneous intracerebral microdialysis and positron emission tomography in the detection of ischemia in patients with subarachnoid hemorrhage.

Intracerebral microdialysis (MD) was applied in patients with subarachnoid hemorrhage. The regional CBF, the CMRO2, and oxygen extraction ratio (OER) were measured with simultaneous positron emission tomography (PET). The aim was to directly correlate alterations in dialysate levels of energy-related metabolites (lactate, lactate/pyruvate ratio, hypoxanthine) and excitatory amino acids (EAAs) (glutamate and aspartate) to the energy state in the MD probe region as determined by PET. Regional ischemia was defined according to Heiss et al. and Lassen (Heiss et al., 1992; Lassen, 1966). Whole-brain ischemia was considered present when the OER for the whole brain exceeded the mean whole-brain OER + 2 SD of six reference patients. In general, the presence of whole-brain ischemia and/or regional ischemia within the region of the MD probe was associated with increased levels of energy-related metabolites and EAAs retrieved by MD. Increased levels of energy-related metabolites and EAAs were only occasionally seen when PET did not show any signs of ischemia or when signs of regional ischemia were found remote from the MD probe region. Thus, the energy-related metabolites and EAAs may be used as extracellular "markers" of ischemia. PET may be of use in defining critical ischemic regions (tissue at risk) where the MD probe can be inserted for chemical monitoring.

Aged↗

PubMed1995

[PET in clinical work. A refined instrument for imaging].

Positron emission tomography (PET) enables in vivo studies to be performed in patients to investigate the binding or metabolism of biologically/functionally active substances labelled with short-lived positron-emitting radionuclides. The procedure has been used for discriminative analysis of physiology and function, both normal and pathological. The range of clinical applications includes studies of cerebral ischaemia and heart diseases, tumor diagnosis and treatment follow-up, presurgical work-up in cases of epilepsy, and characterization and treatment follow-up in cases of dementia. The clinical uses of PET are outlined in a review of the last three years' experience at the PET centre at Uppsala University.

Alzheimer Disease↗

PubMed1995

A method for coregistration of PET and MR brain images.

UNLABELLED: Combining MRI morphological data with functional PET data offers significant advantages in research as well as in many clinical situations. Automatic methods are needed, however, to coregister the data from the two modalities. METHODS: Simulated PET images were created by simple and automatic segmentation of MR images followed by the assignment of different uptake values to various tissue types. The simulated PET images were registered to actual PET images using a pixel-by-pixel, PET-PET registration method. The transformation matrix was then applied to the MR images. The method was used to register MRI data to PET transmission scans and emission scans obtained with FDG, nomifensine and raclopride. Validation was performed by comparing the results to those obtained by matching internal points manually defined in both volumes. RESULTS: Emission and transmission PET images were successfully registered to MR data. Comparison to the manual method indicated a registration accuracy on the order of 1-2 mm in each direction. No difference in accuracy between the different tracers was found. The error sensitivity for the method's assumptions seemed to be sufficiently low to allow complete automation of the method. CONCLUSION: We present a rapid, robust and fully automated method to register PET and MR brain images with sufficient accuracy for most clinical applications.

Adult↗

PubMed1995

End-organ damage in treated severe hypertension: close relation to nocturnal blood pressure.

In an attempt to improve therapeutic decision-making in severe hypertension, different blood pressures (BP) were correlated with target organ damage in a cross-sectional study of 20 asymptomatic patients. Casual BP was 197/117 (s.d. 31/10) mmHg despite therapy. Each subject was assigned an end-organ score on the basis of the number of silent cerebrovascular damages detected by magnetic resonance imaging, funduscopic retinopathy, cardiac hypertrophy by echocardiography, and renal involvement evaluated by isotopic renography. The pooled scores for target organ damage showed significant correlations with an elevated asleep mean ambulatory (amb-) brachial systolic (r = 0.84) and diastolic BP (r = 0.88) but not with either awake amb-BP (means or peak values), causal BP or invasive radial BP at the clinic. Night-time amb-DBP increased with age in contrast to the daytime DBPs. Furthermore, the nocturnal fall in mean arterial amb-BP was significantly less in patients aged > or = 60 years, average 5%, than in patients < 60 years, 16%. This may have prognostic implications even if, after age adjustment, the inverse relation (r = -0.78) between the end-organ scores and the dip in BP did not reach independent significance. The close association of cardiovascular complications with night-time rather than daytime BP emphasises the importance of making a prospective study in this field, trying to optimise the nocturnal BP in severe hypertension.

Adult↗

PubMed1994

Synthesis of fatty acids specifically labelled with 11C in various positions, including 2H substitution, for in vivo studies of myocardium using PET.

Fatty acids were labelled with 11C in several positions by reacting [11C]carbon dioxide with the appropriate Grignard reagent or by reacting a alpha, omega-bis-(bromo magnesium) alkane with a 11C-labelled alkyl iodide followed by a reaction with carbon dioxide. The methyl and methylene 11C-labelled fatty acids were obtained in 12-36% (decay corrected) radiochemical yield within 45-65 min, and with radiochemical purities higher than 96%. Perdeuterated alpha, omega-dibromo hexane, decane and tetradecane were synthesized from dimethylacetylene dicarboxylate by means of a Raney-nickel reduction in D2O, Kolbe electrolysis and LAD reduction. The use of multiple isotopic labelling by the combination of position specific 11C labelling and 2H substitution, has the potential to highlight different aspects of a complex biochemical system by PET. This principle is illustrated by results of the kinetics of different types of 11C label of dodecanoic acid and the corresponding moieties of acetate. The combination of tracers allows the kinetics of beta-oxidation of middle length carbon chain fatty acids and citric acid cycle metabolism to be separately assured, whilst deuteration of the tracers opens the possibility of highlighting the kinetics of the proton extraction processes reflecting rate limiting steps.

Animals↗

PubMed1994

Synthesis of [1-11C], [2-11C], [1-11C](2H3) and [2-11C](2H3)acetate for in vivo studies of myocardium using PET.

Four isotopically-labelled acetates ([1-11C], [2-11C], [1-11C](2H3) and [2-11C](2H3)acetate) were synthesized and used in positron emission tomography (PET) studies of pig myocardium. The [1-11C]acetates were synthesized by carboxylation of the appropriate 1H or 2H methyl Grignard reagents immobilized on a C2 solid phase extraction column (SPE). Purification by reverse-phase HPLC, resulted in 35-45% decay-corrected radiochemical yield with a total synthesis time of 25 min, and a radiochemical purity higher than 99%. The [2-11C]acetates were synthesized by carboxylation of 11C-labelled 1H or 2H methyl lithium. Purification as above resulted in 35-55% decay-corrected radiochemical yield with a total synthesis time of 30 min, and a radiochemical purity higher than 99%. Position-specific labelling was assessed by 13C-labelling and NMR. Multiple isotopic labelling by the combination of position-specific 11C-labelling and 2H substitution, has the potential to highlight different aspects of a complex biochemical system using a selected set of tracers in comparative PET studies. An illustration of this principle is given using acetate, where citric acid cycle metabolism results in a position-specific kinetic for the 11C-label, and deuteration opens up the possibility for the proton-abstracting processes within the citric acid cycle to be assessed.

Acetates↗

PubMed1994

Biexponential pulmonary clearance of 99mTc-DTPA induced by detergent aerosol.

We measured the pulmonary clearance of technetium-99m-labeled diethylenetriamine pentaacetatic acid (99mTc-DTPA) for 3 h after perturbation of the surfactant system by administration of the detergent dioctyl sodium sulfosuccinate in aerosol. Forty-two rabbits were anesthetized with pentobarbital sodium. Tracheostomies were performed, and the rabbits were mechanically ventilated. Increasing concentrations of detergent (0.125-2%) or vehicle were given for 5 min, and clearance measurements were performed immediately or 60 min after detergent administration. No animals developed respiratory distress. After vehicle, the clearance was monoexponential with a half-life of 153 min. Detergent induced a biexponential clearance with a rapidly clearing additional pool of radioactivity with a half-life of 5-15 min. The relative amount of radioactivity clearing rapidly increased with detergent concentration. The detergent effect was partly reversible. We conclude that detergent induces a biexponential clearance of 99mTc-DTPA by accelerating the transfer of tracer across the alveolocapillary barrier in a proportion of lung units in a dose-related manner.

Aerosols↗