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Biomedical subjects

W D Heiss

Publications and source records attributed to W D Heiss.

At least 145 records · Page 8Linked to original sources

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↗

Halothane, but not alpha-chloralose, blocks potassium-evoked cortical spreading depression in cats.

The effects of two anesthetics, halothane and alpha-chloralose, on induction of spreading depression and on extracellular glutamate elevation after intracortical potassium administration were investigated in artificially ventilated (30% oxygen/70% nitrous oxide) cats. High potassium concentrations were achieved using either direct KCl injections (7 microliters, 150 mM via a micropipette) or microdialysis by supplementing 100, 300 or 500 mM KCl, respectively, for 10 min to the perfusion solution (Ringer's). Changes of the cortical DC potential were recorded adjacent (1-2 mm: electrode DC1) and distant (6-7 mm: electrode DC2) to the injection site. Either under halothane (0.75% in the respiratory gas mixture) or under alpha-chloralose (60 mg/kg i.v.) anesthesia, prolonged negative shifts of the DC potential reflecting the elevated potassium levels after KCl injection were measured near the injection site (electrode DC1). In contrast, spreading depressions (transient short DC deflections) were almost exclusively observed under alpha-chloralose. Spreading depressions recorded with electrode DC1 were superimposed on the prolonged negative DC shifts and they propagated frequently to the more distant site (DC2). Upon KCl administration, dose dependent elevations of extracellular glutamate were measured. These elevations were not significantly altered by the type of anesthesia. Our results suggest that in cats, spreading depression induction is affected by anesthesia, i.e., spreading depression induction is inhibited by halothane as compared to alpha-chloralose. Furthermore, factors other than glutamate or high potassium seem to contribute to spreading depression induction.

Animals↗

Hypnotic catalepsy-induced changes of regional cerebral glucose metabolism.

In an attempt to elucidate the physiological basis of hypnosis, we investigated the changes of whole-brain and regional cerebral glucose metabolism, from a state of resting wakefulness to a hypnotized state with whole-body catalepsy, using positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly hypnotizable adults. Neither the random order of study conditions nor any of the other experimental factors had a measurable effect, and there was no statistically significant global activation or metabolic depression. However, repeated measures analysis of variance revealed a statistically significant heterogeneity of symmetric regional responses: Mainly the occipital areas, including visual and paravisual cortex, became relatively deactivated, while some metabolic recruitment was found in structures involved in sensorimotor functions. The observed pattern of changes of regional cerebral activity corresponds with the shift of attention away from normal sensory input that hypnosis is known to produce.

Adult↗

Long-term prognosis of poststroke aphasia studied with positron emission tomography.

OBJECTIVE: To evaluate positron emission tomography with the use of fludeoxyglucose F 18 as a predictor of the long-term outcome of poststroke aphasia. BACKGROUND: Positron emission tomography shows functional deficits after stroke even in morphologically intact brain regions. The regional metabolic impairment can be related to the clinical deficit. Little is known about whether regional hypometabolism early after stroke predicts the long-term prognosis of stroke sequelae. PATIENTS AND METHODS: Twenty-two patients with language disturbance caused by a single lesion in the territory of the left middle cerebral artery were studied with fludeoxyglucose positron emission tomography and with a neuropsychological test battery that included a test of receptive language (Token Test) and a test of word fluency (/f/, /a/, /s/ test). The neuropsychological test was readministered about 2 years after the initial test. RESULTS: Regional cerebral metabolic rates of glucose measured early after stroke showed a highly significant correlation with the results of the 2-year follow-up test. The receptive language disorder best correlated with cerebral metabolic rates of glucose in the left superior temporal cortex, and word fluency correlated with cerebral metabolic rates of glucose in the left prefrontal cortex. CONCLUSION: Cerebral metabolic rates of glucose in speech-relevant brain regions measured early after stroke are a predictor of the eventual outcome of aphasia.

Aged↗

Planum temporale and Brodmann's area 22. Magnetic resonance imaging and high-resolution positron emission tomography demonstrate functional left-right asymmetry.

OBJECTIVE: To describe the registered analysis of magnetic resonance imaging and glucose metabolic data acquired with positron emission tomography to determine the relationship between structure and function of temporal lobe cortical structures between the left and right hemispheres. BACKGROUND: The dominance of the left cerebral hemisphere is associated with a preponderance of the left planum temporale. SUBJECTS AND METHODS: Fifteen subjects without signs or symptoms of a neurological disorder. Three-dimensional-registered magnetic resonance imaging and positron emission tomography with the use of fludeoxyglucose F18 and a high-resolution positron emission tomography scanner. Analysis of regional metabolic activation during single-word repetition on matched parasagittal magnetic resonance imaging and positron emission tomography. RESULTS: The planum temporale was bilaterally activated without left-right asymmetry. The metabolic increase was asymmetric within the left Brodmann's area (BA) 22. The part of the left BA 22 that was buried in the superior temporal sulcus was significantly less activated than the part of BA 22 on the surface of the superior temporal gyrus. The metabolic activation in the sulcal part of the left BA 22 had a significant inverse correlation with the anatomical predominance of the left planum temporale (r = .71, P = .003) and a significant direct correlation with the metabolic activation in the surface aspects of the right BA 22 (r = .82, P < .001). CONCLUSION: Brodmann's area 22 is a critical feature of language dominance and is also important with regard to the exchange of information between the two hemispheres.

Adult↗

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↗

Neurological sequelae of cyanide intoxication--the patterns of clinical, magnetic resonance imaging, and positron emission tomography findings.

We report 2 patients with neurological sequelae of oral cyanide intoxication who were evaluated clinically and neuropsychologically, with high-resolution magnetic resonance imaging and one of them with positron emission tomography. The clinical syndrome was characterized by extrapyramidal motor and cerebellar symptoms such as bradykinesia, hypomimia, slowed speech, anteropulsion, and marked retropulsion, but little tremor. The sensory and pyramidal motor systems were normal or relatively spared. On neuropsychological testing the intellectual capacity and memory functions were normal, whereas the speed of motor reaction and verbal fluency were reduced. Magnetic resonance imaging showed damage of the globus pallidus, putamen, substantia nigra, subthalamic nucleus, and cerebellum in both patients, whereas the sensory-motor cortex and hippocampus were relatively spared. 18F-6-Fluoro-dopa positron emission tomography revealed a symmetrical reduction of striatal dopa uptake by 42% on average that was similar in the putamen and caudate. 18F-2-Fluoro-2-deoxyglucose positron emission tomography showed a regional reduction of the glucose metabolism in the posterior putamen and temporo-parieto-occipital and cerebellar cortex.

Adult↗

Cognitive impairment in Alzheimer's disease correlates with ventricular width and atrophy-corrected cortical glucose metabolism.

We compared the correlation of PET and MRI with neuropsychological tests in 26 patients with probable Alzheimer's disease (AD). The width of the temporal horns and the third ventricle, regional metabolic rates of glucose (rCMRGlu) and the proportion of cerebrospinal fluid space in mesial temporal and temporoparietal cortical regions were measured with three-dimensionally coregistered PET and MRI in two planes perpendicular to the Sylvian fissure. Highly significant correlations between rCMRGlu and neuropsychological tests were found mainly in the temporoparietal cortex, with and without correction for atrophy. Correlations of similar magnitude were seen also between most tests and the width of the temporal horns and third ventricle. Changes in the third ventricle and mesial temporal lobe were best seen with MRI, whereas PET most clearly depicted alterations in neocortical association areas. These two aspects of the disease correlated with the severity of dementia to a similar degree.

Aged↗

P300 in Alzheimer's disease: relationships to dementia severity and glucose metabolism.

In 45 patients (aged 48-85 years) with probable Alzheimer's disease (AD) according to current research criteria (NINCDS-ADRDA) with different stages of dementia severity (Mini Mental Status Examination (MMSE) 7-27) the auditory evoked P300 waves were mapped and regional cerebral metabolic rates of glucose were measured by positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose. Age adjusted P300 latency was significantly correlated to dementia severity (r = -0.33, p = 0.028), but no significant relationships were found for P300 amplitudes. Dependencies existed among cortical glucose metabolic rates and MMSE with the highest correlation coefficient for the metabolic ratio of regions typically affected and non-affected in AD (r = 0.75, p = 0.0001). A significant correlation was also calculated between P300 latency and metabolic ratio (r = -0.44, p = 0.002), but no relationships were observed among P300 amplitudes and glucose metabolic rates of individual brain regions. These results indicate that P300 latency and metabolic rates but not P300 amplitudes qualify as measures of severity in AD. The lack of regional correlations among P300 amplitudes and glucose metabolism is not consistent with a cortical contribution to P300 generation.

Aged↗

Regional cerebral blood flow and metabolism in Sturge-Weber disease.

A 50-year-old man with Sturge-Weber syndrome (SWS) and left cerebral hemisphere atrophy was studied using PET with O-15 oxygen and O-15 water in order to evaluate regional cerebral blood flow and energy metabolism in this condition. PET demonstrated decreased perfusion and increased oxygen extraction fraction in the affected left cerebral hemisphere and ipsilateral cerebellum. These findings suggest that a chronic state of reduced perfusion may be the etiology for the cerebral hemiatrophy seen in some patients with SWS.

Cerebrovascular Circulation↗

Metabolic changes in acute and subacute cerebral infarctions: findings at proton MR spectroscopic imaging.

PURPOSE: To analyze the advantages of proton magnetic resonance (MR) spectroscopic imaging in the evaluation of acute and subacute cerebral infarcts. MATERIALS AND METHODS: Metabolite maps of choline-containing compounds, total creatine consisting of creatine and phosphocreatine, N-acetyl aspartate (NAA), and lactate were obtained in 23 patients with acute and subacute cerebral infarctions 1-35 days after onset of symptoms. Maps were obtained with a 1.5-T MR system with 32 x 32 phase-encoding steps. RESULTS: Distinct abnormal metabolite distributions could be detected in all lesions larger than 1 cm in diameter. In the center of infarcts with a diameter larger than the section thickness of 2 cm, NAA values decreased to 20% +/- 8 compared with contralateral brain as early as 1 day after onset of symptoms (P < .0001). Choline was reduced to 67% +/- 30 (not significant) and creatine to 51% +/- 22 (P = .0025). Large amounts of lactate were detected in all acute infarcts. Choline, creatine, and lactate values declined during the first 5 weeks after stroke. CONCLUSION: MR spectroscopic imaging allows visualization of metabolic changes in stroke with a reasonable spatial resolution.

Acute Disease↗

Dysfunction of visual cortex contributes to disturbed processing of visual information in Alzheimer's disease.

The relation between visual impairment and regional cerebral metabolic rate of glucose (rCMRGl) was studied in 31 patients with probable Alzheimer's disease (AD) by using positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose. To exclude any precortical cause of visual dysfunction only patients were included who had amplitudes and latencies of visually evoked potentials (flash and pattern reversal) within the normal range. Visual information processing was evaluated psychometrically by a fragmented picture test (FPT), which is a combined perception (identification score) and memory (reidentification score) task and refers to Gollin's incomplete pictures. The identification and reidentification scores were significantly worse than in normals. Reductions of the rCMRGl in the primary visual fields, and in the secondary visual fields were found. A significant partial correlation with adjustment for age between the reidentification score of the FPT and the rCMRGl of the secondary visual fields (r = -.39, p < .05) in AD patients was found, indicating involvement of the secondary visual cortex in the pathological changes in AD.

Aged↗

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↗

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↗

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↗

Assessment of pathophysiology of stroke by positron emission tomography.

In stroke patients, multitracer positron emission tomography (PET) permits the assessment of acute changes in regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen consumption (rCMRO2) and glucose metabolism (rCMRgl), which are the initial steps in the complex molecular and biochemical process leading to ischaemic cell damage. While early infarcts exhibit low flow and oxygen consumption, increased oxygen extraction fraction (OEF) due to preserved metabolism at reduced flow suggests viability of tissue. However, most initially "viable" tissue will be metabolically deranged and will become necrotic in the further course; only in a few instances do these tissue compartments recover to normal function. Increased glucose uptake at reduced oxygen supply induces non-oxidative glycolysis with noxious lactacidosis, whereas hyperperfusion beyond the metabolic demand is of controversial effect. In subacute or chronic states after ischaemia reduced flow can be compensated by increased blood volume; when perfusional reserve is exhausted, oxygen extraction increases. Such findings may guide therapeutic decisions and predict the severity of permanent deficits. Functional deactivation of tissue remote from the lesion is found regularly as a sign of damaged connecting pathways. Flow and metabolic studies during the performance of specific tasks help to detect alternative functional loops and may yield prognostic information. Repeat studies in the course of stroke are employed for the evaluation of therapeutic strategies targeted to improve reperfusion or to effect metabolic or biochemical alterations. In the future PET may gain additional clinical importance when patients are selected for elective treatment according to the prevailing pathophysiological pattern.

Animals↗

HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison of perfusion and metabolic pattern.

Positron emission tomography (PET) of 18F-2-fluoro-2-deoxy-D-glucose (FDG) and single-photon emission tomography (SPET) of 99mTc-hexamethylpropylene amine oxime (HMPAO) were performed under identical resting conditions within 3 h in 20 patients with probable Alzheimer's disease (AD), 12 patients with vascular dementia (VD) and 13 normal persons. In the temporoparietal association cortex similar impairment of relative regional cerebral glucose metabolism (rCMRGl) and relative HMPAO uptake (rCBF) was found. In addition PET showed hypometabolism in the occipital association cortex. The functional pattern was condensed to a ratio of regional values of association areas divided by regional values of structures that are typically less affected by AD. In normals this ratio was significantly related to age for PET metabolic data (r = -0.66, P = 0.01). The ratio was significantly lower in AD than in VD and controls for both rCMRGl and rCBF. In AD only, the metabolic ratio was related to severity of dementia (r = 0.54, P = 0.003) and age (r = 0.64, P = 0.003). Metabolic differences between normals and AD patients were less obvious in old age. In contrast, there were no significant correlations between the perfusion ratio and severity of dementia or age. Comparing the metabolic and perfusion ratio by receiver operating characteristic curves, PET differentiated AD from normals only marginally better than SPET. Differentiation between AD and VD was much better achieved by PET. Our results suggest that both PET and SPET can distinguish AD patients from controls, whereas for differentiation between AD and VD SPET is of little value.

Aged↗

Quantitative topographical EEG compared to FDG PET for classification of vascular and degenerative dementia.

Quantitative topographical EEG was compared with regional glucose metabolism measured by PET with respect to the sensitivity in the classification of mild to moderate dementia. In 24 patients with probable Alzheimer's disease (DAT), 19 patients with vascular dementia (VD) and 15 age-matched healthy controls, global and regional EEG and PET data were analyzed. The metabolic ratio between typically affected and non-affected regions differentiated between DAT and VD (P < 0.001) as well as between DAT and normal controls (P < 0.001) even for the subgroup of mild dementia. In contrast to PET, global EEG changes were more sensitive than regional alterations for the classification into the respective groups. Relative theta power was most sensitive for the differentiation of demented patients irrespective of type of normal controls (P < 0.01), whereas OCC/FR alpha ratio (occipital divided by frontal power) separated between dementia types (P < 0.01) as well as between DAT and normals (P < 0.05). Additionally, EEG may help to grade severity especially in DAT. Combined use of EEG and PET was more discriminative and reached higher diagnostic specificity than each test individually. These results suggest that EEG and PET are complementary diagnostic procedures for the differentiation and classification of dementias.

Aged↗