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K Wienhard

Publications and source records attributed to K Wienhard.

At least 37 records · Page 2Linked to original sources
PubMed1998

Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke.

BACKGROUND AND PURPOSE: Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since gamma-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [11C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas. METHODS: In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke. RESULTS: In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO2 was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO2 (<60 micromol/100 g per minute) corresponded to regions with decreased FMZ binding (<4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow. CONCLUSIONS: These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies.

Aged↗
PubMed1998

11C-methionine PET for differential diagnosis of low-grade gliomas.

Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.

Adult↗
PubMed1998

[F-qi-FDG PET of the thyroid gland in Graves' disease].

AIM: This study evaluates F-18-FDG PET of the thyroid in Graves' disease. METHODS: Thirty patients were investigated the day before radioiodine therapy, 15 patients 3-10 days after radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. RESULTS: F-18-FDG uptake was higher in Graves' disease patients than in controls. Negative correlations of F-18-FDG uptake with half-life of radioiodine and absorbed radiation dose due to radioiodine therapy were found along with a positive correlation to autoantibody levels. CONCLUSION: Thus F-18-FDG PET is likely to give information on the biological activity of Graves' disease as well as on early radiation effects.

Adult↗
PubMed1997

Functional effects of striatal dysfunction in Parkinson disease.

BACKGROUND: Concepts of basal ganglia organization suggest structually and functionally segregated pathways that link putamen and caudate function to motor and cognitive performance, respectively. OBJECTIVE: To investigate whether motor and cognitive impairment in Parkinson disease is attributable to selective disturbance in nigrostriatal, dopaminergic function and regional cerebral glucose metabolism. DESIGN: Twenty patients with probable Parkinson disease underwent positron emission tomographic measurements of dopaminergic, nigrostriatal function (positron emission tomography with fluorodopa F 18), regional glucose metabolism (positron emission tomography with fludeoxyglucose F 18), memory testing, and evaluation of locomotor disability. RESULTS: Memory performance in the patient cohort strongly correlated with the individual disease duration and degree of locomotor disability (P < .05). Striatal uptake rates of fluorodopa F 18 were significantly reduced in all patients (P < .05) compared with those in normal control subjects, and putaminal rates correlated significantly with the patients' degree of locomotor disability (P < .01) but not with memory performance. In the patients with an advanced stage of disease, there was a significant correlation between reduced caudate uptake rates of fluorodopa F 18 and the patients' impairment in delayed recall performance of the memory task (P < .05) but not with the individual degree of locomotor disability. No changes were found for regional glucose metabolic rates in the patients compared with the controls. CONCLUSIONS: The present study provides evidence for the hypothesis that on the level of the striatum, motor impairment in Parkinson disease may be assigned to altered dopamine neuronal integrity in the putamen but not in the caudate, whereas memory impairment in the more advanced cases may be attributed to caudate but not putaminal dysfunction.

Aged↗
PubMed1997

Spatial transformation during 3D reconstruction in positron emission tomography.

Spatial transformations of positron emission tomographic data for aligning images or transforming to standard anatomical space are usually performed with reconstructed images. However, they can also be performed during the reconstruction process, thereby interpolating the raw data fewer times. We investigated the performance of spatial transformations during reconstruction, implemented it in a standard 3D reconstruction algorithm, and tested it on phantom and patient H215O activation studies for the application of aligning both transmission and emission scans. Performing the transformations during reconstruction was shown to be equivalent to performing the transformations with reconstructed images for this particular application.

Algorithms↗
PubMed1997

Performance of a randomization test for single-subject (15)O-water PET activation studies.

We adapted and implemented a permutation test (Holmes 1994) to single-subject positron emission tomography (PET) activation studies with multiple replications of conditions. That test determines the experimentwise alpha error as well as location and extent of focal activations in each individual. Its performance was assessed in five normal volunteers, using (15)O-H2O-PET data acquired on a high-resolution scanner, with septa retracted (3D mode), during functional activation by repeating words versus resting (four replications each). Calculated alpha errors decreased and the size of activated tissue volumes (voxels with P < or = 0.05) increased with increasing filter kernel size applied to the difference images. At a filter kernel of 12 mm Gaussian full width at half maximum, significant focal activations were seen bilaterally in superior temporal cortex, including Brodmann's areas 41 and 42, in all five subjects. Additional foci were detected in the precentral gyrus, left inferior frontal gyrus, supplementary motor area, and cerebellum of several subjects. The average CBF increase in activated voxels ranged from 17.6% to 28.7%. Activated volumes were smaller than those detected with a standard parametric test procedure. We conclude that the permutation test is a less sensitive procedure, having the advantage of not depending on unproven distributional assumptions, that detects strong activation foci in individual subjects with high reproducibility.

Adult↗
PubMed1997

Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats.

BACKGROUND AND PURPOSE: Ligands for cerebral benzodiazepine receptors were used in the past to indicate the intactness of cortical neurons in subacute to chronic states after stroke and thus to differentiate among brain regions with complete or incomplete infarction and with functional deactivation. For planning acute interventional therapy, however, a marker of irreversible damage in early ischemia is needed. We studied the applicability of [11C]flumazenil (FMZ) for differentiation between tissue with and without potential of recovery in the first hours after focal experimental ischemia. METHODS: In 11 cats, cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction, and FMZ binding were studied repeatedly by positron emission tomography before, during, and up to 12 hours after transient middle cerebral artery occlusion (MCAO) (30 minutes in 2, 60 minutes in 7, and 120 minutes in 2 cats, respectively). Development of the defects in energy metabolism were compared with the defects in FMZ binding (2 to 3 hours and 8 to 9 hours after MCAO), with the pattern of disturbed glucose metabolism (determined 12 hours after MCAO), and with the size of the infarcts (determined approximately 15 hours after MCAO). RESULTS: Irrespective of the level of reperfusion, defects in FMZ binding (2 to 3 hours after MCAO) were closely related to areas with severely depressed oxygen consumption and predicted the size of the final infarcts, whereas preserved FMZ binding indicated intact cortex. Depression of glucose metabolism was in all animals larger than the defects in FMZ binding and the infarcts, indicating functional deactivation of brain areas beyond the permanent morphological damage. In addition, FMZ distribution within 2 minutes after injection was significantly correlated to flow and yielded reliable perfusion images. CONCLUSIONS: The reduction of FMZ binding early after focal ischemia reflects irreversible neuronal damage that otherwise only can be detected by multitracer studies. Our experimental data and first clinical applications suggest that FMZ has potential as an indicator of developing infarction. Since FMZ distribution additionally images perfusion, this tracer might be useful for the selection of patients who would benefit from acute therapeutic intervention.

Animals↗
PubMed1996

MRI-guided flumazenil- and FDG-PET in temporal lobe epilepsy.

In temporal lobe epilepsy (TLE) patients without lesions, major hippocampal sclerosis, or atrophy on magnetic resonance imaging (MRI), the localizing power of [11C]flumazenil (FMZ) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was compared using high-resolution positron emission tomography (PET) studies and individually coregistered MRI scans. Following complete clinical, neuropsychological, and electrophysiological evaluation, benzodiazepine receptor density was assessed using the FMZ equilibrium method. Thirty minutes later, interictal FDG-PET was performed under resting conditions. PET images were matched to three-dimensionally coregistered, T1-weighted MRI. Each temporal lobe (TL) was divided into 12 volumes of interest. The regional FMZ data were normalized with respect to average cortical values. For each patient the right-left asymmetries of rCMRGlc and normalized FMZ data were calculated. In 7 to 10 patients, mesial TL structures showed reduced FMZ binding, with a decrease by at least 10% in the affected TL. Reductions of 10% or more of rCMRGlc usually were more widespread than FMZ reductions and often involved lateral temporal cortex. The regions of most pronounced disturbances are not necessarily identical in both methods. Three patients had a complex correspondence of lateralization with PET, neuropsychological, and EEG data. In 4 patients, lateralization was less clear from EEG or neuropsychological results but was still consistent with lateralization by PET. In 3 of 10 patients, however, major discrepancies were found. These data suggest that the combination of neuropsychological testing, EEG, and MRI-guided FMZ- and FDG-PET will help to select patients with clearly defined epileptogenic foci especially in mesial TLE. Even in cases without MRI lesions, TL epileptic foci can be lateralized with consistency across the methods; FMZ-PET shows the pathologic focus more circumscribed than FDG-PET.

Adult↗
PubMed1996

Individual functional anatomy of verb generation.

Examination of the individual functional anatomy of language is of particular interest in clinical neurology to explain the variability of aphasic symptoms after focal lesions and to avoid damage of language-related brain areas by surgery. For a silent verb generation task, we examined whether activation PET with 3D data acquisition, multiple replication of conditions, and coregistration with MRI provides results that are consistent and reproducible enough to be useful clinically. Visual analysis was performed on PET-MRI fusion images, including renderings of the brain surface. Quantitative analysis was based on volumes of interest. In seven right-handed normals, activation of the triangular part of the left inferior frontal cortex [Brodman area (BA) 45] was the most significant finding that was present in each subject. Two subjects showed minor anatomical variants of the ascending or horizontal ramus of the sylvian fissure that were associated with the least activation of BA 45. In the left hemisphere the other frontal gyri, the superior temporal and posterior part of the middle temporal gyrus, and the paracingulate gyrus were also significantly activated. There was significant bilateral cerebellar activation, but it was significantly more intense on the right than on the left side. The consistency and high interindividual reproducibility of these findings suggest that this technique may be useful for clinical assessment of language-related areas.

Acoustic Stimulation↗
PubMed1996

Vascular dementia: perfusional and metabolic disturbances and effects of therapy.

Positron emission tomography (PET) has elucidated basic pathophysiological mechanism that produce the cognitive decline in vascular dementia (VD). The typical pattern of glucose metabolism seen in VD with scattered areas of focal cortical and subcortical hypometabolism differs from that in AD with marked hypometabolism affecting the association areas. The total volume of metabolically inactive tissue is significantly related to severity of dementia. Rather than the quantity of tissue destruction, the critical effect may be the quantity of cortical hypometabolism caused by subcortically induced disconnection. Studies with HMPAO SPECT have shown focal deficits in VD and AD patients that are comparable to those seen with FDG PET. In mildly demented patients performance for the classification AD versus VD is much better by PET because it might be more sensitive for imaging small functional pathological changes. A longitudinal analysis of rCMRGl in VD showed that the progression of dementia can be delayed by the adenosine uptake blocker propentofylline and that neuropsychological and metabolic changes are closely related.

Brain↗
PubMed1996

Diaschisis of specific cerebellar lobules: pontine haematoma studied with high-resolution PET and MRI.

Cerebellar glucose metabolism was studied in one patient with a hemipontine haematoma in order to investigate remote metabolic effects within the cerebellar lobules. In the patient, who suffered a circumscribed hemipontine haemorrhage, and in three normal subjects cerebellar glucose metabolisms was studied using 18F-2-fluoro-2-deoxy-D-glucose and high-resolution positron emission tomography (PET). Regions of interest were placed on sagittal brain slices of co-registered magnetic resonance images for quantitative evaluation of glucose metabolism in each cerebellar lobule. Interruption of corticopontine fibres caused inactivation of pontine nuclei with subsequent contralateral cerebellar diaschisis, mainly in the anterior lobe and the posterior portion of the quadrangular lobule. Damage within the ponto-cerebellar part of the cortico-ponto-cerebellar pathway, e.g. pontine nuclei and crossing ponto-cerebellar fibres from contralateral pontine nuclei, led to ipsi- and contralateral cerebellar diaschisis within the semilunar, gracile and biventral lobules. High-resolution PET is capable of demonstrating bilateral diaschisis involving specific cerebellar lobules to a different degree that is consistent with the pontine anatomy of the cortico-ponto-cerebellar pathway and with the location of the haemorrhagic lesion.

Adult↗
PubMed1996

Temporal lobe epilepsy: evidence for interictal uncoupling of blood flow and glucose metabolism in temporomesial structures.

Measurements of regional cerebral glucose metabolism (rCMRGlc) and blood flow (rCBF) are widely considered exchangeable for the detection of dysfunctional zones in temporal lobe epilepsy (TLE). However, the underlying assumption of preserved coupling of rCBF and rcMRGlc is questionable and requires verification. Thirteen patients with unilateral mesiolimbic TLE underwent interictal positron emission tomography (PET) measurements of rCBF using [15(O)]butanol and of rcMRGlc using (18)FDG. rcMRGlc, rCBF and glucose extraction fraction (rGEF) were obtained from temporomesial and temporolateral structures. When compared to the respective homotopic contralateral reference region, in temporomesial structures ipsilateral to the EEG-defined focus ('dysfunctional zone'), average rCMRGlc and rGEF were decreased while rCBF was unaffected. Analysis of (18)FDG kinetics revealed that (18)FDG transport was unaltered but the hexokinase reaction was specifically decreased. In the temporolateral structures, no such mismatch between metabolism and blood flow was observed. In mesiolimbic TLE, interictal rCMRGlc-PET is superior to rCBF-PET with respect to the sensitivity to detect regional functional abnormalities. This seems to be due to focal uncoupling of glucose metabolism and blood-brain barrier transport or blood flow. We hypothesize that the observed uncoupling of transport and metabolism may be characteristic of epileptogenic zones in TLE of typical etiology.

Adult↗
PubMed1996

F-Dopa as an amino acid tracer to detect brain tumors.

A 57-yr-old woman suffering from light movement disorder of the left arm and hand was referred for 18F-Dopa PET. The PET study not only proved asymmetrically reduced dopamine uptake in the putamen (influx constant Ki right 0.0064/min, left 0.0086) but also revealed pathologically increased 18F-Dopa accumulation in the right frontal lobe. Further PET examinations demonstrated increased 11C-methionine uptake and low glucose metabolism in this right frontal region. MRI and 1H-MRSI showed a heterogeneous lesion with reduced N-acetyl-aspartate and increased choline and lactate, suggesting a mixed, low-grade glioma. In 15O-water studies, during intentional movements of one hand the respective motor areas were identified, indicating asymmetries due to the mass occupying lesion. The tumor could be removed in open surgery, thus sparing the motor areas; a mild postoperative motor deficit resolved to the presurgical state. Histology confirmed the diagnosis of a grade 2 oligo-astrocytoma. This case impressively demonstrates that 18F-Dopa can be used as an amino acid tracer for brain tumor detection in addition to its established application to assess aromatic acid decarboxylase activity.

Brain↗
PubMed1995

Positron emission tomography and magnetic resonance spectroscopy of cerebral glycolysis in children with congenital lactic acidosis.

Congenital lactic acidosis with neurological symptoms may be due to a variety of disorders of energy metabolism. We investigated whether positron emission tomography (PET) and proton magnetic resonance spectroscopy (1H MRS) are capable of demonstrating specific changes to facilitate diagnosis. A corresponding increase of cerebral lactate (with MRS) and rate of glycolysis (with PET) was observed in 2 children with biochemical evidence of defective mitochondrial respiration. No such increase was noted in a child with lactic acidosis due to stress and exercise but normal respiratory chain activity, and in a control case with an epilepsy syndrome without evidence of primary changes of energy metabolism. The results suggest that defects of oxidative phosphorylation may cause a massive increase of glycolysis to cover energy requirements, with corresponding accumulation of lactate in brain tissue. This mechanism can now be demonstrated in vivo and, with further experience, may potentially be used as a diagnostic marker of respiratory chain disorders in brain tissue.

Acidosis, Lactic↗
PubMed1995

Effect of tissue heterogeneity on quantification in positron emission tomography.

As a result of the limited spatial resolution of positron emission tomographic scanners, the measurements of physiological parameters are compromised by tissue heterogeneity. The effect of tissue heterogeneity on a number of parameters was studied by simulation and an analytical method. Five common tracer models were assessed. The input and tissue response functions were assumed to be free from noise and systematic errors. The kinetic model was assumed to be perfect. Two components with different kinetics were mixed in different proportions and contrast with respect to the model parameters. Different experimental protocols were investigated. Of three methods investigated for the measurement of cerebral blood flow (CBF) (steady state, dynamic, integral), the second one was least sensitive to errors caused by tissue heterogeneity and the main effect was an underestimation of the distribution volume. With the steady state method, errors in oxygen extraction fraction caused by tissue heterogeneity were always found to be less than the corresponding errors in CBF. For myocardial blood flow the steady state method was found to perform better than the bolus method. The net accumulation of substrate (i.e. rCMRglc in the case of glucose analogs) was found to be comparatively insensitive to tissue heterogeneity. Individual rate constants such as k2 and k3 for efflux and metabolism of the substrate in the pool of unmetabolized substrate in the tissue, respectively, were found to be more sensitive. In studies of radioligand binding, using only tracer doses, the effect of tissue heterogeneity on the parameter kon.Bmax could be considerable. In studies of radioligand binding using a protocol with two experiments, one with high and one with low specific activity, Bmax was found to be insensitive while Kd was very sensitive to tissue heterogeneity.

Body Water↗
PubMed1995

High-resolution PET in cats: application of a clinical camera to experimental studies.

UNLABELLED: A commercial high-resolution scanner designed for clinical PET studies was tested for its applicability to investigate cerebral metabolism and blood flow in cats. METHODS: Cerebral blood flow, CMRO2, CBV and CMRglc were determined repeatedly using 15O steady-state oxygen methods and 18F-fluorodeoxyglucose (FDG). Metabolic and blood flow images of 14 contiguous 3-mm PET slices were compared to histological sections in four control animals. In another six cats, hemodynamic and metabolic changes were followed by serial multi-tracer PET for 24 hr after permanent occlusion of the left middle cerebral artery (MCA). Pattern and extent of changes of the physiological variables were related to the final infarct verified in matched histological sections. RESULTS: At spatial resolutions (FWHM) of 3.6 mm in transaxial planes and 4.0 mm axially, details of the gross anatomy of the cat brain were distinguished best in the FDG images. Cerebral blood flow, CMRO2 and CMRglc values measured in the cortex, white matter and basal ganglia were in the range of common autoradiographic results. Immediately after MCA occlusion, there was widespread decrease in blood flow, but metabolism was preserved at values, which suggest viable tissue. With time, the areas of increased oxygen extraction fraction (OEF) moved from the center to the periphery of the MCA territory. CONCLUSION: High-resolution PET can be used for repeat, quantitative imaging of blood flow and metabolism in small animals such as the cat. After MCA occlusion, the changes in blood flow and metabolism can be followed over time and can be related to the final morphological lesion.

Animals↗