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Biomedical subjects

A Buck

Publications and source records attributed to A Buck.

At least 55 records · Page 3Linked to original sources

Human hippocampus associates information in memory.

The hippocampal formation, one of the most complex and vulnerable brain structures, is recognized as a crucial brain area subserving human long-term memory. Yet, its specific functions in memory are controversial. Recent experimental results suggest that the hippocampal contribution to human memory is limited to episodic memory, novelty detection, semantic (deep) processing of information, and spatial memory. We measured the regional cerebral blood flow by positron-emission tomography while healthy volunteers learned pairs of words with different learning strategies. These led to different forms of learning, allowing us to test the degree to which they challenge hippocampal function. Neither novelty detection nor depth of processing activated the hippocampal formation as much as semantically associating the primarily unrelated words in memory. This is compelling evidence for another function of the human hippocampal formation in memory: establishing semantic associations.

Adult↗

Synthesis and in Vivo studies of [C-11]N-methylepibatidine: comparison of the stereoisomers.

The carbon-11-labelled nicotinic acetylcholine receptor (nAChR) agonist N-methylepibatidine was evaluated in vitro and in vivo as a possible positron emission tomography (PET)-tracer for nicotinic receptors in the central nervous system (CNS). The racemic mixture and both enantiomers of N-methylepibatidine were compared. Biodistribution and metabolites for blood and brain of [C-11]N-methylepibatidine were determined in mice. Whole body rat PET data were acquired for both stereoisomers. The regional distribution of the N-methyl-(-)-epibatidine in the brain was determined by a PET scan in a pig. Characteristic differences were found for the in vivo behavior of the stereoisomers of [C-11]N-methylepibatidine.

Animals↗

Monocyte-derived dendritic cells as a model for the study of HIV-1 infection: productive infection and phenotypic changes during culture in human serum.

Dendritic cells (DC) have been implicated in the initial selection for macrophage-tropic HIV-1 during transmission and in the generation of high-level virus replication during interactions with CD4 T cells. The role of DC as viral reservoirs and the extent of productive infection is unclear, but the ability to generate large numbers of DC from blood monocytes has produced a tractable model for study of DC-HIV-1 interactions. When cultured in granulocyte-macrophage colony stimulating factor and IL-4, sorted CD14+ monocytes rapidly lost phagocytic function for both 93 nm and 977 nm latex particles and developed the surface markers and function of DC. After 7 days, when returned to medium containing human serum without cytokines, some monocyte-derived dendritic cells (MDDC) became adherent, but retained the costimulatory markers CD80 and CD86 and continued to express CD83 and CD40. The MDDC stimulated allogeneic CD4 T cells, did not express new macrophage markers and remained non-phagocytic. With or without TNF-alpha, MDDC generated in cytokines were infected by macrophage and T cell-tropic virus and produced higher reverse transcriptase levels than did the autologous monocyte-derived macrophages (MDM). When added to T cells, the infected MDDC were able to infect T cells with a wider range of viral isolates than were MDM.

Antigens, CD↗

Relation between neuropsychological and neuroimaging findings in patients with late whiplash syndrome.

OBJECTIVES: The interpretation of long term cognitive impairment after whiplash injury is still a problem for many physicians. On the grounds of nuclear medicine findings previous research speculated that brain damage is responsible for cognitive problems of patients with whiplash. To test this hypothesis the relation between neuroimaging and neuropsychological findings was analysed. METHODS: Twenty one patients (11 women, 10 men, mean age 42.2 (SD 8.6) years) with the late whiplash syndrome (average interval of trauma 26.1 (SD 20.7) months) referred for diagnostic action to the Department of Neurology were investigated. Assessment included computer assisted assessment of working memory and divided attention, neuroimaging (by the means of [99mTc]-HMPAO-SPECT, [15O]-H2O-PET and [18F]-FDG-PET), testing of emotional functioning (depression and anxiety ratings), and pain intensity at the time of testing. RESULTS: On average, scoring on tests of cognitive functioning was very low. However, no significant correlations were found between regional perfusion or metabolism in any brain area and the scores of divided attention or working memory. By contrast, significant relations were found between indices of impaired emotional functioning (state anxiety) and divided attention. In addition, low scoring in divided attention was significantly correlated with pain intensity at the time of testing. CONCLUSIONS: The present data do not provide evidence of a significant relation between detectable morphological or functional brain damage and impaired cognitive performance in the late whiplash syndrome. Results indicate triggering of emotional and cognitive symptoms on the basis of initial injury of the cervical spine.

Adult↗

Activation of the left motor cortex during left leg movements after right central resection.

A patient with Rasmussen's encephalitis underwent a right central resection at the age of 6 as a treatment for status epilepticus. She became seizure free, but suffered a left hemiplegia which improved so that she could walk. Because of the recurrence of seizures an enlargement of the resection to a hemispherectomy was carried out 17 years after the first operation. Various examinations, including H(2)(15)O PET and amytal testing, performed before this second operation indicated that a compensatory reinforcement of the ipsilateral uncrossed corticospinal and spinocortical pathways had taken place. This was confirmed postoperatively. The patient had no new sensorimotor deficits.

Adult↗

[F-18-FDG PET for primary diagnosis differential diagnosis of pleural processes].

PURPOSE: Positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) has been shown to be accurate for differentiating benign from malignant pulmonary lesions. Therefore, we evaluated the capability of FDG-PET in the characterisation of pleural lesions. PATIENTS AND METHODS: PET was performed in thirteen patients with pleural or intrapulmonal tumors (three with additional pleural effusion) and in three patients with aetiologically unclear pleural effusion demonstrated by CT. In all cases the diagnosis was confirmed histologically. The PET-imaging was carried out in fasted patients 50 minutes after injection of 400-670 MBq F-18-FDG without attenuation correction. RESULTS: Twelve patients were found to have pleural or pulmonal malignomas (9 pleural mesotheliomas, 3 bronchogenic adenocarcinoma with carcinomatous pleurisy). Four patients had benign pleural changes (1 fibroma, 1 tuberculous pleurisy, 1 pleural fibrosis, 1 empyema). With FDG-PET, all 12 pleural or intrapulmonal malignomas had high FDG-uptake and were classified correctly. Due to very low or virtually deficient FDG-uptake, four histologically benign lesions were correctly interpreted as nonmalignant. CONCLUSION: These preliminary results suggest that FDG-PET is accurate in detecting malignant pleural tumors.

Adult↗

Monoamine oxidase B single-photon emission tomography with [123I]Ro 43-0463: imaging in volunteers and patients with temporal lobe epilepsy.

Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various neurological diseases. In the past non-invasive assessment of MAO B has only been possible with positron emission tomography (PET) ligands. Given the limited availability of PET, a single-photon emission tomography (SPET) ligand would be desirable. In this study SPET imaging with the new MAO B inhibitor [123I]Ro 43-0463 was performed in five volunteers and nine patients with temporal lobe epilepsy (TLE). In two volunteers a second study was performed 12 h following blockade with deprenyl. In the TLE patients the tracer was administered as bolus (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated well with the known distribution of MAO B. In the two blocking studies ligand uptake was substantially reduced compared with baseline. In the TLE patients increased uptake was found in the ipsilateral mesial temporal lobe and, surprisingly, in the ipsilateral putamen. This study indicates the potential of the new SPET ligand [123I]Ro 43-0463 to map MAO B concentration in the human brain. The new finding of increased MAO B in the putamen of TLE patients needs further studies to elucidate its exact pathophysiology.

Adult↗

Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma: effectiveness and comparison with computed tomography.

The purpose of this study was to evaluate whole-body positron emission tomography (WB-PET) as a staging modality in Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL) and to compare it with computed tomography (CT) in a retrospective study. Seventy-one WB-PET studies using fluorodeoxyglucose (FDG) and 49 CT examinations were performed in 19 women and 31 men. Transaxial images were acquired and reformatted coronally and sagittally in PET. CT sections were obtained from the skull base to the pelvic floor. The written reports of the imaging data were compared with a reference standard constructed on the basis of all the data on the individual patients, including clinical follow-up of at least 6 months. The sensitivity and specificity of PET were, respectively, 86% and 96% for HD (n=53), and 89% and 100% for NHL (n=18). For CT sensitivity and specificity were 81% and 41% for HD (n=33) and 86% and 67% for NHL (n=16). Differences between PET and CT sensitivities were not significant, while in HD there was a significant difference in the specificity of PET and CT examinations, mainly because CT was unable to distinguish between active or recurrent disease and residual scar tissue after therapy. FDG tumour uptake was found in high- as well as low-grade NHL patients. In conclusion, PET appears to be highly sensitive and specific for staging of lymphoma. It is at least as sensitive as CT, and more specific, particularly in patients undergoing restaging, where a well-recognized diagnostic dilemma in CT is the presence of a post-therapeutic residual mass.

Adolescent↗

In vivo properties of N-(2-aminoethyl)-5-halogeno-2-pyridinecarboxamide 18F- and 123I-labelled reversible inhibitors of monoamine oxidase B.

The reversible and highly selective monoamine oxidase B (MAO-B) inhibitor Ro 19-6327, a picolinic acid derivative, was selected for the development of new radiopharmaceuticals, whereby in place of Cl either 123I or 18F was introduced. The respective labelling procedures have been described earlier. In this study, some metabolic properties were investigated. Blood and urine samples were analysed, and halogenated picolinylglycine, a more hydrophilic compound, was identified as the main metabolite. This shows that the amine is oxidised to the respective carboxylate, but the intermediate imine or aldehyde that was proposed earlier could not be detected. First experiments with single photon emission tomography and positron emission tomography (PET) showed that the iodo compound can be used to investigate MAO-B in vivo while the fluoro compound is accumulated in the brain to such a low degree that no PET studies can be performed. We conclude that the main reason for the poor uptake of the fluoro compound is its lower lipophilicity as compared to the iodo compound and, to a lesser degree, its metabolism, which is similar for both compounds.

Adult↗

Changes of cerebral blood flow during short-term exposure to normobaric hypoxia.

Decreased arterial partial oxygen pressure (PaO2) below a certain level presents a strong stimulus for increasing cerebral blood flow. Although several field studies examined the time course of global cerebral blood flow (gCBF) changes during hypoxia at high altitude, little was known about the regional differences in the flow pattern. Positron emission tomography (PET) with [(15)O]H2O was used on eight healthy volunteers to assess regional cerebral blood flow (rCBF) during short-term exposure to hypoxia corresponding to simulated altitudes of 3,000 and 4,500 m. Scans at the simulated altitudes were preceded and followed by baseline scans at the altitude of Zurich (450 m, baseline-1 and baseline-2). Each altitude stage lasted 20 minutes. From baseline to 4,500 m, gCBF increased from 34.4 +/- 5.9 to 41.6 +/- 9.0 mL x minute(-1) x 100 g(-1) (mean +/- SD), whereas no significant change was noted at 3,000 m. During baseline-2 the flow values returned to those of baseline-1. Statistical parametric mapping identified the hypothalamus as the only region with excessively increased blood flow at 4,500 m (+32.8% +/- 21.9% relative to baseline-1). The corresponding value for the thalamus, the structure with the second largest increase, was 19.2% +/- 16.3%. Compared with the rest of the brain, an excessive increase of blood flow during acute exposure to hypoxia is found in the hypothalamus. The functional implications are at present unclear. Further studies of this finding should elucidate its meaning and especially focus on a potential association with the symptoms of acute mountain sickness.

Adult↗

Selective amobarbital test for the determination of language function in patients with epilepsy with frontal and posterior temporal brain lesions.

PURPOSE: Selective amobarbital tests with selective temporary inactivation of the left frontal operculum and/or the left parietotemporal cortex were performed in 5 patients with left-hemispheric epileptogenic lesions in or adjacent to classical Broca's and/or Wernicke's area. The aim was to assess language functions in these brain regions before surgery, to tailor the surgery according to the individual functional importance of these brain regions, and to predict postoperative outcome. METHODS: Amobarbital was injected by transfemoral selective catheterization of the arteries supplying the target areas. Along with neuropsychological and neurological testing during the amobarbital procedure, EEG recordings were performed in all patients, and [99mTc]HMPAO-single photon emission computed tomography (SPECT) in 2 patients. RESULTS: After the amobarbital injection into the left frontal opercular region, there was no recognizable language dysfunction in 3 patients. In these 3 patients, the lesions in or adjacent to the frontal operculum were completely resected without postoperative language impairment. In the remaining 2 patients, temporary language impairment after the amobarbital injection into the left frontoopercular and Wernicke's region, respectively, suggested language functions in these areas. Surgery was restricted to the left mesiotemporal lobe in 1 patient. In the other patient, the tumor infiltrating the frontal operculum was restrictively resected. Postoperatively, the first patient had no language impairment, but the latter had transient global aphasia, from which she recovered. CONCLUSIONS: Selective temporary amobarbital inactivation of brain regions that may be associated with language has clearly indicated the presence or absence of language functions in these regions. The test contributed substantially to planning of the surgical approach in each patient. The predictive value of the amobarbital test was demonstrated by the postoperative outcome.

Adolescent↗

PET with 18fluorodeoxyglucose and hexamethylpropylene amine oxime SPECT in late whiplash syndrome.

BACKGROUND: Many patients have cognitive abnormalities and psychological problems after whiplash injury to the cervical spine. To our knowledge, neuroradiologic imaging has not depicted brain damage that explains the symptoms. Parietotemporo-occipital perfusion deficits on hexamethylpropylene amine oxime (HMPAO) SPECT studies have been described among patients who have sustained whiplash injury. METHODS: We examined 13 patients with typical late whiplash syndrome (study group) using HMPAO SPECT, 18fluorodeoxyglucose (FDG) PET, and MRI of the brain and compared the findings with those for 16 control subjects who underwent FDG PET. RESULTS: In the study group, statistical parametric mapping revealed significantly decreased FDG uptake in the frontopolar and lateral temporal cortex and in the putamen. The frontopolar hypometabolism correlated significantly with scores of the Beck Depression Inventory. However, in individual cases, reliability in the depiction of hypometabolic areas was relatively low. No alterations were found in the parietotemporo-occipital area. In these areas, decreased uptake of HMPAO and FDG correlated with cortical mass. CONCLUSION: FDG PET did not allow reliable diagnosis of metabolic disturbances for individual patients. Therefore, we do not recommend FDG PET or HMPAO SPECT as a diagnostic tool in routine examinations of patients with late whiplash syndrome.

Adult↗

Planar coincidence scintigraphy and PET in staging malignant melanoma.

UNLABELLED: This study describes a comparison of simulated planar positron coincidence scintigraphy (PCS) with PET in the whole-body staging of patients with malignant melanoma using 2-18F-fluoro-2-deoxy-D-glucose (FDG). METHODS: In 55 patients with either known metastatic or newly diagnosed malignant melanoma, whole-body PET scanning was performed on a conventional full-ring dedicated PET tomograph, and multiaxial sections were obtained. Furthermore, anteroposterior projection images simulating images of a dual-head Anger camera operating in coincidence mode were obtained from the PET raw data. Each study was evaluated separately and blindly. Imaging findings were confirmed by biopsy or by at least one imaging modality in addition to PET. RESULTS: A total of 108 lesions were evaluated, of which 76 proved to be melanoma metastases. Whole-body PET correctly demonstrated 68 metastases, 6 lesions were classified as questionable metastases and 2 were missed. Whole-body PCS correctly demonstrated 14 metastases, 22 lesions were classified as questionable metastases and 40 metastases were missed. The sensitivities of whole-body PET and whole-body PCS were 89% and 18%, respectively. In PCS lesions in regions of high background activity, such as in the abdomen, were missed more often than in PET (p < 0.05). The tumor-to-background contrast was generally lower in PCS than in PET. A further decrease in PCS detection was found in lesions of < 22 mm in diameter. CONCLUSION: The lack of sensitivity precludes the clinical use of whole-body PCS in staging malignant melanoma.

Adult↗

Human hippocampus establishes associations in memory.

Studies of amnesia have demonstrated that the hippocampus is necessary for long-term memory, but its precise role in memory is unknown. We designed a positron emission tomography experiment with tailored encoding and retrieval tasks that permitted the isolation of different mnemonic functions theorized to be mediated by the hippocampus. These functions included encoding single items, establishing interitem associations, novelty detection, and retrieving recently formed associations. Of these, we found hippocampal and parahippocampal activation only during associative learning. Our results indicate that the hippocampal formation may be particularly involved in the establishment of associations among components of an episode in memory.

Association↗

The anterior and posterior selective temporal lobe amobarbital tests: angiographic, clinical, electroencephalographic, PET, SPECT findings, and memory performance.

The techniques, results, and problems of three types of selective temporal lobe (TL) amobarbital procedures (balloon technique with temporary occlusion of the internal carotid artery distal to the origin of the anterior choroidal artery (acha) [n = 19]; selective anterior catheterization of the acha [n = 20]; and selective catheterization of the peduncular P2-segment of the posterior cerebral artery [n = 5]) are described in a group of 40 patients with medically refractory complex partial seizures of mesial TL origin. Selective amobarbital tests were carried out before surgery to predict the memory deficit after an intended selective amygdalohippocampectomy. The effects of selective anaesthetization of TL were correlated with clinical data, pattern and duration of amobarbital induced EEG changes, and performance on verbal and nonverbal memory tasks measured during the test. In 4 patients the effect of selective amobarbital injection on regional and global metabolism was studied with 18F-FDG-PET, with the PET tracer being injected intravenously immediately after amobarbital. More recently in 2 patients the vascular territory perfused by amobarbital in the acha test was studied with SPECT using 99m Tc ECD injected immediately prior to the amobarbital into the acha. Whereas the PET studies showed a rather widespread and bilateral amobarbital-induced decrease of metabolism, the SPECT studies confirmed the selective distribution of the tracer in the vascular territory of the acha, i.e., in amygdala and hippocampus. The comparison of selective TL amobarbital test performance with postoperative neuropsychological performance showed that the predictive value of this test is rather good for the postoperative verbal memory but underestimates postoperative nonverbal ("figural") memory performance.

Adult↗

Musicogenic epilepsy: review of the literature and case report with ictal single photon emission computed tomography.

PURPOSE: We report a case of musicogenic epilepsy with ictal single photon emission computed tomography (SPECT) study and discuss the findings of this patient in the context of 76 cases with musicogenic epilepsy described in the literature and seven other cases followed in Zurich. METHODS: We analyzed the 83 patients according to the precipitating musical factors, type of epilepsy, presumed localization of seizure onset, and demographic data. RESULTS: Fourteen of 83 patients (17%) had seizures triggered exclusively by music. At time of examination, music was the only known precipitating stimulus in 65 of 83 patients (78%). Various characteristics of the musical stimulus were significant, e.g., musical category, familiarity, and instruments. CONCLUSIONS: Musicogenic epilepsy is a particular form of epilepsy with a strong correlation to the temporal lobe and a right-sided preponderance. A high musial standard might predispose for musicogenic epilepsy. Moreover, the majority of cases do not fall into the category of a strictly defined "reflex epilepsy," but appear to depend on the indermediary of a certain emotional reaction mediated through limbic mesial temporal lobe structures.

Acoustic Stimulation↗

Requirements and implementation of a flexible kinetic modeling tool.

UNLABELLED: Kinetic (or compartment) modeling is a highly versatile tool for the analysis of experiments within living systems. In PET, it is essential for developing tracers, for assessing tracer behavior and for extracting quantitative information about the target process. However, tools to support the modeling tasks involved are not easily available. METHODS: This article presents a requirements analysis for kinetic modeling in PET. The interactive kinetic modeling tool KMZ implements many of these features. It facilitates model development by a set of predefined models and by the ease of introducing new models. Monte Carlo studies allow assessing parameter identifiability. The responses in the different compartments as well as the expected time-activity curve can be simulated for specific model configurations. For measured time-activity curves, model optimization can be performed by the Powell or the Marquardt algorithm. Both support weighted nonlinear least-squares fitting and allow optional constraints of parameter ranges. To further improve parameter estimation, the fitting of several regional time-activity curves can be coupled, resulting in lower standard errors for parameters common among regions. It is possible to highly automate the evaluation of study series and to forward the results into statistical analysis tools. RESULTS: The KMZ tool has proven highly suitable in evaluating data from different types of studies, and the intuitive user interface enables medical doctors to successfully perform routine evaluations after a short training period. CONCLUSION: A portable kinetic modeling tool with the described features would provide easy access to model development and may help consolidate kinetic modeling in clinical settings for well-defined applications.

Algorithms↗

Tracer kinetic modelling of receptor data with mathematical metabolite correction.

Quantitation of metabolic processes with dynamic positron emission tomography (PET) and tracer kinetic modelling relies on the time course of authentic ligand in plasma, i.e. the input curve. The determination of the latter often requires the measurement of labelled metabolites, a laborious procedure. In this study we examined the possibility of mathematical metabolite correction, which might obviate the need for actual metabolite measurements. Mathematical metabolite correction was implemented by estimating the input curve together with kinetic tissue parameters. The general feasibility of the approach was evaluated in a Monte Carlo simulation using a two tissue compartment model. The method was then applied to a series of five human carbon-11 iomazenil PET studies. The measured cerebral tissue time-activity curves were fitted with a single tissue compartment model. For mathematical metabolite correction the input curve following the peak was approximated by a sum of three decaying exponentials, the amplitudes and characteristic half-times of which were then estimated by the fitting routine. In the simulation study the parameters used to generate synthetic tissue time-activity curves (K1-k4) were refitted with reasonable identifiability when using mathematical metabolite correction. Absolute quantitation of distribution volumes was found to be possible provided that the metabolite and the kinetic models are adequate. If the kinetic model is oversimplified, the linearity of the correlation between true and estimated distribution volumes is still maintained, although the linear regression becomes dependent on the input curve. These simulation results were confirmed when applying mathematical metabolite correction to the [11C]iomazenil study. Estimates of the distribution volume calculated with a measured input curve were linearly related to the estimates calculated using mathematical metabolite correction with correlation coefficients >0.990. However, the slope of the regression line displayed considerable variability among the subjects (0.33-0.95), demonstrating that absolute quantitation of the distribution volume was impaired. Mathematical metabolite correction is a feasible method and may prove useful in cases where actual metabolite data cannot be obtained. The potential for absolute quantitation seems limited, but the method allows the quantitative assessment of regional ratios of receptor measures.

Adult↗