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K Wienhard

Publications and source records attributed to K Wienhard.

At least 55 records · Page 3Linked to original sources
PubMed1994

Individual metabolic anatomy of repeating words demonstrated by MRI-guided positron emission tomography.

The anatomical localization of brain areas involved in repeating words was examined in six right-handed non-aphasic subjects. Their individual metabolic activation was studied with positron emission tomography (PET) and [18F]2-fluoro-2-deoxy-D-glucose (FDG) using a new data processing technique that includes three-dimensional coregistration with magnetic resonance images. Left superior temporal gyrus (cortical convexity surface, Brodmann area 22), right superior temporal lobe (superior temporal sulcus and bottom of transverse sulcus), sensorimotor cortex (vocalization area) bilaterally, and supplementary motor cortex were consistently activated in each individual. Cerebellar activation was more variable. In contrast to previous blood flow activation studies with averaging across subjects, this new technique permits the anatomical localization and quantitation of activated areas in each individual. It can therefore also be applied to patients with brain lesions.

Adult↗
PubMed1994

Discordant twins with Parkinson's disease: positron emission tomography and early signs of impaired cognitive circuits.

We evaluated 7 pairs of twins (2 monozygotic and 5 dizygotic) discordant for Parkinson's disease (PD), of whom the cotwins showed no signs of motor impairment on neurological examination. All subjects underwent positron emission tomographic measurements of cerebral glucose metabolism and dopaminergic, nigrostriatal function following injection of 2-[18F]fluoro-2-deoxy-D-glucose and L-6-[18F]fluorodopa ([18F]dopa), respectively, as well as testing for anterograde, verbal episodic, and semantic memory performance. Statistical analysis demonstrated significant reduction of striatal [18F]dopa uptake not only in the twin patients with PD but also in all of the cotwins, who showed significantly (p < 0.05) impaired [18F]dopa metabolism in at least one of the striatal measures including caudate, putaminal, and the rostrocaudal putaminal gradient of [18F]dopa uptake. Compared with age-matched controls, regional glucose metabolism was unchanged in all the twins. Neuropsychological testing showed significant (p < 0.05) impairment in verbal memory processing in the twin patients with PD and in 6 of the cotwins. Semantic memory skills were affected in 2 twin patients only. A significant correlation was found between scores obtained in Buschke's Selective Reminding Test and striatal [18F]dopa uptake, further substantiating the role of dopaminergic pathways in memory processing. The present study is the first to reveal not only significant disturbance of nigrostriatal dopaminergic function in verbal episodic memory that is known to be affected in PD. Larger studies with a longitudinal design will be necessary to answer the question of whether cognitive changes found in the cotwin group are signs of incipient PD.

Aged↗
PubMed1994

Automatic control device for the continuous administration of (15)O labeled gaseous tracers for PET measurements.

An automatic control device for the administration of (15)O labelled gaseous PET tracers with constant dose per time (continuous inhalation) is presented. The system controls the flow through the target, the flow to the patient and the dose to the patient simultaneously. The desired values for the dose and the flow to the patient are variable. The dose to the patient is kept constant with +/- 4% even if the beam current raises or if the beam is off for some seconds.

Administration, Inhalation↗
PubMed1994

Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats.

Experimental models of focal cerebral ischemia have provided important data on early circulatory and biochemical changes, but typically their correspondence with metabolic and hemodynamic findings in stroke patients has been poor. To fill the gap between experimental studies at early time points and rather late clinical studies, we repeatedly measured CBF, CMRO2, oxygen extraction fraction (OEF), cerebral blood volume (CBV), and CMRglc in six cats before and up to 24 h after permanent middle cerebral artery (MCA) occlusion (MCAO), using the 15O steady state and [18F]fluorodeoxy-glucose methods and a high-resolution positron emission tomography (PET) scanner. Likewise, three sham-operated control cats were studied during the same period. Final infarct size was determined on serial histologic sections. In the areas of final glucose metabolic depression that were slightly larger than the histologic infarcts, mean CBF dropped to approximately 40% of control values immediately on arterial occlusion. If further decreased to < 20% during the course of the experiment. This progressive ischemia was most conspicuous in border zones. CMRO2 fell to a lesser degree (55%), eventually reaching approximately 25% of its control level. At early stages, OEF increased mainly in the center of ischemia. With time, areas of increased OEF moved from the center to the periphery of the MCA territory. Concurrently, progressive secondary decreases in OEF in conjunction with further reductions of CBF and CMRO2 indicated the development of central necrosis. The findings are highly suggestive of a dynamic penumbra. In five cats with complete MCA infarcts, CBF decreased and OEF increased in the contralateral hemisphere after 24 h, suggesting whole-brain damage. This effect may be explained by the widespread brain edema found histologically in addition to the nonspecific CBF reductions and OEF elevations observed also in the sham-operated controls after 1 day in the experimental condition. In one cat, cortical OEF increased only transiently. Normal CMRO2 and CMRglc were eventually restored, and the final infarct was small. This study demonstrates that acute regional pathophysiologic changes can be repeatedly assessed by multivariate PET in cats. Viable tissue can be detected up to several hours after MCA occlusion, and the transition of misery-perfused regions into necrosis or preserved tissue can be followed over time. The present results support the concept of a dynamic penumbra, in which for up to 24 h tissue damage spreads progressively from the center to the periphery of ischemia. Sequential high-resolution PET provides insight into the dynamics of regional pathophysiology and may thus further the development of rational therapeutic strategies.

Animals↗
PubMed1994

[Assessing myocardial viability in chronic myocardial infarct with 18F-fluoro-D-glucose positron emission tomography and 99mTc-MIBI SPECT].

The determination of residual viability in regions of myocardial infarcts is of considerable clinical interest. In order to assess residual viability in regions with chronic myocardial infarction, 18 patients with anterior myocardial infarcts and 14 patients with inferior myocardial infarcts as confirmed by ECG and cine ventriculography underwent 99mTc-methoxyisobutyl-isonitrile single photon emission computed tomography (MIBI-SPECT) and 18F-fluoro-D-glucose positron emission tomography (FDG-PET). Tracer uptake was quantified in 13 segments for each patient (a total of 416 segments). MIBI uptake was normalized to the maximal uptake in the heart, FDG uptake was normalized to the maximal uptake of left ventricular segments with normal contraction by cine ventriculography and without significant stenosis of the coronary artery supplying this region. MIBI-SPECT scar and FDG-PET scar were defined as tracer uptake of less than 2.5 SD below mean values of a healthy control group. Both methods scored 258 segments concordantly viable and 74 segments concordantly scar; 61 segments were scored scar by MIBI-SPECT and viable by FDG-PET, 23 segments were scored viable by MIBI-SPECT and scar by FDG-PET (p < 0.0001). In patients with anterior myocardial infarction, 136 segments were scored viable and 53 segments were scored scar by both methods, 29 segments were scored scar by MIBI-SPECT and viable by FDG-PET, 16 were scored discordantly viable by MIBI-SPECT and scar by FDG-PET (p < 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Single-breath inhalation or rebreathing of gases labelled with positron emitters: some technical aspects of dispensing and waste gas management.

A simple and reliable system for the single-breath inhalation and for short-term rebreathing of radioactive gases used in positron emission tomography is described. It comprises a collection- and radioactivity measurement-device, an inhalation bag for single-breath application, a modified anaesthetic system for rebreathing and a patient exhaled gas management system. The system is mainly used with 15O-labelled gases, but allows also the use of longer lived tracers such as methyl fluoride labelled with 18F or 11C.

Administration, Inhalation↗
PubMed1992

The FDG model and its application in clinical PET studies.

The FDG method, as it is applied in clinical PET studies is reviewed. The influence of different implementations of the method and instrumental inaccuracies on the values of cerebral metabolic rate of glucose is discussed. For the comparison of the results between different groups standardized procedures are recommended.

Data Interpretation, Statistical↗
PubMed1992

Positron emission tomography in degenerative disorders of the dopaminergic system.

21 patients who had Parkinson's disease (PD), PD plus dementia of Alzheimer type (PDAT) or progressive supranuclear palsy (PSP), were studied with positron emission tomography (PET) using (18F)-2-fluoro-2-deoxy-D-glucose (FDG). In one patient with strictly unilateral PD side differences in striatal dopa uptake were studied with 6-(18F)fluoro-L-dopa (F-dopa). In patients with PD PET with FDG did not show any significant change in regional cerebral metabolic rates for glucose (rCMR(Glu)). In PDAT glucose metabolism was generally reduced, the most severe decrease was found in parietal cortex. The metabolic pattern was similar to that typically found in patients with Alzheimer's disease (AD). In the patient with strictly unilateral PD rCMR(Glu) was normal, F-dopa PET, however, revealed a distinct reduction of dopa uptake in the contralateral putamen. In PSP glucose metabolism was significantly decreased in subcortical regions (caudatum, putamen and brainstem) and in frontal cortex. Thus PET demonstrated a clear difference of metabolic pattern between PDAT and PSP.

Adult↗
PubMed1992

Progressive derangement of periinfarct viable tissue in ischemic stroke.

Sixteen patients were studied by multitracer positron emission tomography (PET) within 6-48 (mean of 23) h of onset of a hemispheric ischemic stroke and again 13-25 (mean of 15.6) days later. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) were measured each time by standard methods, and the sets of brain slices obtained at the two studies were matched using a three-dimensional alignment procedure. On matched brain slices, regions of interest (ROIs) for infarct and peri-infarct tissue, contralateral mirror regions, and major brain structures were outlined. In the core of infarction, blood flow and metabolism were significantly lower than in the corresponding contralateral regions at the first study, and did not change during the observation period. In the peri-infarct tissue, CMRO2 was moderately decreased at the first measurement; over time, the CMRO2 deteriorated progressively while flow did not change. When peri-infarct regions were selected on the basis of increased OEF (25 +/- 29.8% above corresponding contralateral regions) on the early scans, the CBF was significantly decreased (23 +/- 6.6%) while the CMRO2 showed only a slight difference from the mirror region. Within the observation period, the CBF improved but the CMRO2, OEF, and CMRglc deteriorated. Only in a few regions with increased OEF and slightly impaired CMRO2 was metabolism preserved close to normal values. These data from repeat PET studies in reproducibly defined tissue compartments furnish evidence of viable tissue in the border zone of ischemia up to 48 h after stroke. While this viable peri-infarct tissue exhibits some potential for effective treatment of ischemic stroke, therapeutic routines available today cannot prevent subsequent metabolic derangement and progression to necrosis. Multitracer PET studies identifying viable tissue could be of value in the development of effective treatment of ischemic stroke.

Adolescent↗
PubMed1991

Positron emission tomography with (18F)methylspiperone demonstrates D2 dopamine receptor binding differences of clozapine and haloperidol.

Four schizophrenic patients were investigated with dynamic positron emission tomography (PET) using (18F)fluorodeoxyglucose (FDG) and (18F)methylspiperone (MSP) as tracers. Two schizophrenics were on haloperidol therapy at the time of MSP PET. The other two schizophrenics were treated with clozapine, in one of them MSP PET was carried out twice with different daily doses (100 mg and 450 mg respectively). Neuroleptic serum levels were measured in all patients. Results were compared with MSP PET of two drug-free male control subjects and with a previous fluoroethylspiperone (FESP) study of normals. Three hours after tracer injection specific binding of MSP was observed in the striatum in all cases. The striatum to cerebellum ratio was used to estimate the degree of neuroleptic-caused striatal D2 dopamine receptor occupancy. In the haloperidol treated patients MSP binding was significantly decreased, whereas in the clozapine treated patients striatum to cerebellum ratio was normal. Even the increase of clozapine dose in the same patient had no influence on this ratio. Despite the smaller number of patients the study shows for the first time in humans that striatal MSP binding reflects the different D2 dopamine receptor affinities of clozapine and haloperidol.

Adult↗
PubMed1991

Quantification of baboon cortical S2 serotonin receptors in vivo with 3-N-(2'-F18)fluoroethylspiperone and positron emission tomography.

We used the ligand 3-N-(2'-F18)fluoroethylspiperone (FESP) and positron emission tomography (PET) to quantify in vivo serotonin S2 neuroreceptor density and affinity in the baboon frontal cortex. In the cortex, FESP binds specifically and exclusively to S2 receptors, and an equilibrium is reached when the rate of ligand-receptor association and dissociation become equal. Using multiple studies in the same baboon, an equilibrium (saturation) analysis approach provided a linear Hill plot with a slope of 1.02 (r2 = 0.988, P less than 0.0001), indicative of ligand binding to a single receptor class. Using serial PET scans, a dynamic approach was also used to quantify S2 receptors in the frontal cortex of the baboon, which provided an estimate of receptor density Bmax = 35.6 +/- 10.9 pmol/g. The rate constants corresponding to transport into and out of tissue were K1* = 0.2720 +/- 0.0299 mol/min.g and k2* = 0.0786 +/- 0.0315 min-1, respectively. The ligand-receptor dissociation constant was k4* = 0.0154 +/- 0.0109 min-1.

Animals↗
PubMed1991

Estimation of local cerebral glucose utilization by positron emission tomography: comparison of [18F]2-fluoro-2-deoxy-D-glucose and [18F]2-fluoro-2-deoxy-D-mannose in patients with focal brain lesions.

A comparative PET study of [18F]2-fluoro-2-deoxy-D-glucose (FDG) and [18F]2-fluoro-2-deoxy-D-mannose (FDM) uptake was performed in 13 patients with focal brain lesions. Differences between FDG and FDM with respect to model rate constants, lumped constant, and estimated metabolic rate for glucose were determined on a regional basis. Across whole brain, the transport rate constant K1* was almost unchanged, whereas k2*, describing the transport back from tissue to plasma, was 6% higher, and the phosphorylation rate constant k3* was 9% lower for FDM compared to FDG. This implies a 20% lower lumped constant for FDM. No significant regional variability of this differential tracer behavior was observed in normal or in lesioned brain tissue. Thus, results from previous FDG studies, where the radiotracer was not 100% pure FDG but contained varying amounts of FDM, can easily be corrected by adjustment of the lumped constant employed in metabolic quantitation.

Adult↗
PubMed1991

Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine.

The uptake of L-(2-18F)fluorotyrosine (F-Tyr), a newly synthetized amino acid tracer, was studied in 15 patients with various brain tumors by dynamic PET. The higher F-Tyr accumulation in tumors (mean 27% above contralateral tissue) was associated with two-fold transport rates into tumors, while the rate constants describing irreversible incorporation were decreased. The increased F-Tyr transport was not correlated to 68Ga-EDTA accumulation and cannot be explained by disruption of the blood-brain barrier. Kinetic analysis of 2-(18F)-fluoro-deoxy-glucose accumulation in the same patients demonstrated that increased metabolic rates in tumors are mainly caused by altered phosphorylation rates while transport of glucose is less affected. Since F-Tyr transport rates clearly separated tumors from normal tissue and since F-Tyr accumulation was related to tumor grade, PET studies of F-Tyr uptake are of clinical value for diagnosis and classification of brain tumors.

Adult↗
PubMed1990

PET studies of dopamine receptor distribution using [18F]fluoroethylspiperone: findings in disorders related to the dopaminergic system.

PET studies of dopamine D2-receptor binding were performed in thirty patients with various disorders related to the dopaminergic system and in six healthy controls. Uptake of [18F]fluoroethylspiperone in caudate over three hours was analyzed in terms of several indices of receptor binding:caudate-to-cerebellum activity ratio, concentration of ligand as percentage of injected dose, caudate-to-blood radioactivity ratio, slope of tracer uptake curves, binding potential, kinetic constants of a three compartment model. In 14 patients brain glucose metabolism was also measured. Data on medicated patients demonstrate that the average values of most of the above parameters indicate the decreased number of available D2-receptors whereby, besides an age dependent decline, the caudate-to-cerebellum ratio affords the relatively best distinction among diagnostic groups. In individual cases, large variability among subjects permits only the classification of severe pathologies. Morphological damage and neuronal loss in the striatum may also cause abnormal low values both for the indices of receptor binding and for glucose consumption, thus providing a possible pathogenetic link between receptor dysfunction and impaired energy metabolism.

Adolescent↗
PubMed1990

The quantitative analysis of D2-dopamine receptors in baboon striatum in vivo with 3-N-[2'-18F]fluoroethylspiperone using positron emission tomography.

We used the ligand 3-N-[2'-18F]fluoroethylspiperone (FESP), which binds to D2-dopamine receptors in the striatum, and positron emission tomography (PET) to quantify striatal D2-dopamine densities (Bmax) and binding kinetics in baboon brain in vivo. Sequential PET scans were obtained for 4 h post injection. Various similar models based on a nonlinear kinetic four-compartment model that takes into account the effect of ligand specific activity were used. We investigated the effect of exact model configuration on the reliability of Bmax and other kinetic transfer coefficients. We found that with the ligand FESP and dynamic PET studies, the estimated values of Bmax and other model parameters are sensitive to the choice of model configuration, ligand specific activity, and data analysis technique. The limitations of the reliability of parameter estimates in a complex kinetic model for receptor ligands were studied in simulation calculations. Results showed that the accuracy of estimated values of Bmax is affected by both the ligand binding properties and the injected dose of ligand. The estimated average value of kinetic model parameters was as follows: ligand-receptor dissociation constant k4 = 0.0080 min-1; the product of ligand-receptor association constant and fraction of ligand available to bind to specific receptors f2ka = 0.0052 (min nM)-1; and D2-dopamine receptor density Bmax = 37.5 pmol g-1.

Animals↗
PubMed1990

Validity of PET studies in brain tumors.

Positron emission tomography (PET) in human brain tumors presents specific problems, such as tissue inhomogeneity and disruption of the blood-brain barrier (BBB), that are not present or at least not that important in normal brain. In addition, tracer metabolism may be different from normal brain. Mathematical arguments demonstrate that quantitation in inhomogeneous tissue is extremely difficult with tracers undergoing reversible metabolism, whereas irreversible metabolic steps can be quantified more easily. Even for metabolically inert tracers with reversible transport across the BBB, physiological identification of transport rate constants may be ambiguous, since diffusion processes within the tissue cannot be differentiated from slow transport components at the BBB. Mathematical analysis shows that transport is usually underestimated, whereas metabolism is usually overestimated in inhomogeneous tumor tissue. For accurate measurements of blood flow and BBB permeability, use of short measurement times is recommended. Measurements of tumor glucose consumption with [18F]2-fluoro-2-deoxy-D-glucose (FDG) are probably only little affected by tumor heterogeneity. There are, however, major problems caused by variation of the lumped constant, which relates the kinetics of FDG to those of glucose. Most experimental data indicate a considerable increase of the lumped constant in malignant tumors, resulting in overestimation of glucose metabolism if the standard value is used. In spite of these limitations, measurements of glucose metabolism with FDG are useful clinically to evaluate the prognosis of patients with brain tumors and to differentiate between late radiation necrosis and recurrent tumor. New tracers for measurement of protein synthesis, cell proliferation, and uptake of cytostatic drugs are of high clinical interest. As yet, little is known about the contribution of metabolites in brain and plasma to measured tissue activity, and differentiation between transport at the BBB and metabolism may be difficult. Therefore, the basis for accurate quantitation with these new compounds is still incomplete. Clinical reports suggest that some amino acid tracers can be used for localization and grading of brain tumors.

Amino Acids↗