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W Burchert

Publications and source records attributed to W Burchert.

At least 37 records · Page 2Linked to original sources

Neural mechanisms of global and local processing. A combined PET and ERP study.

The neural mechanisms of hierarchical stimulus processing were investigated using a combined event-related potentials (ERPs) and positron emission tomography (PET) approach. Healthy subjects were tested under two conditions that involved selective or divided attention between local and global levels of hierarchical letter stimuli in order to determine whether and where hemispheric differences might exist in the processing of local versus global information. When attention was divided between global and local levels, the N2 component of the ERPs (260- to 360-msec latency) elicited by the target stimuli showed asymmetries in amplitude over the two hemispheres. The N2 to local targets was larger over the left hemisphere, but the N2 to global targets tended to be slightly larger over the right hemisphere. However, the shorter-latency, sensory-evoked P1 component (90- to 150-msec latency) was not different for global versus local targets under conditions of divided attention. In contrast, during selective attention to either global or local targets, asymmetries in the N2 component were not observed. But under selective attention conditions, the sensory-evoked P1 components in the extrastriate cortex were enlarged for global versus local attention. Increased regional cerebral blood flow in the posterior fusiform gyrus bilaterally was observed in the PET data during selective attention to either global or local targets, but neither these nor the P1 component showed any tendency toward hemispheric difference for global versus local attention. Neither were there any activations observed in the parietal lobe during selective attention to global versus local targets. Together these data indicate that early sensory inputs are not modulated to gate global versus local information differentially into the two hemispheres. Rather, later stages of processing that may be asymmetrically organized in the left and right hemispheres operate in parallel to process global and local aspects of complex stimuli (i.e., the N2 effect of the ERPs). This pattern of results supports models proposing that spatial frequency analysis is only asymmetric at higher stages of perceptual processing and not at the earliest stages of visual cortical analysis.

Adult↗

[18F]fluoride PET indicates reduced bone formation in severe glucocorticoid-induced osteoporosis.

A 61-year-old female patient presenting with mixed connective tissue disease (Sharp syndrome), underwent a long-term high dose glucocorticoid treatment because of multiple organ manifestations. Under steroid therapy she developed severe osteoporosis resulting in multiple fractures. A dynamic [18F]fluoride PET study in this patient revealed reduced fluoride influx in non-fractured vertebrae. This finding corresponds to pathogenetic concepts which propose an inhibition of bone formation as major cause of glucocorticoid-induced osteoporosis. In the light of the presented case it seems to be promising to evaluate the diagnostic benefit of [18F]fluoride PET in osteoporosis.

Esophagus↗

Assessment of myocardial viability by use of 11C-acetate and positron emission tomography. Threshold criteria of reversible dysfunction.

BACKGROUND: Dual positron emission tomography (PET) imaging with a perfusion tracer and 18F-fluorodeoxyglucose (FDG) can detect myocardial viability. This approach may be replaced by a single 11C-acetate study, which enables quantification of both regional blood flow and oxidative metabolism. The significance of acetate-derived indexes for myocardial viability is examined. METHODS AND RESULTS: Thirty postinfarct patients with akinetic ventricular segments, a mean ejection fraction of 42 +/- 11%, and high-grade coronary obstructions were studied with serial 11C-acetate PET scanning before and 7 +/- 5 months after coronary revascularization. Acetate PET was tested against FDG and serial assessments of segmental wall motion. Sixty of 155 severely dysfunctional LV segments improved postoperatively, and regional blood flow increased. Flow estimates after revascularization suggested little fibrosis in reversible segments. At baseline, blood flows differed between normal myocardium, reversible dysfunction, and irreversible dysfunction (1.04 +/- 0.27, 0.73 +/- 0.18, and 0.43 +/- 0.18 mL.min-1.g-1, respectively; P < .001). Oxidative metabolic rates were reduced only in irreversibly injured LV segments. Multivariate analysis identified the acetate perfusion index as the only independent predictor of postoperative recovery. Its predictive accuracy was similar to that of FDG imaging but superior to indexes of flow-metabolic mismatch or oxidative metabolism. CONCLUSIONS: After myocardial infarction, quantitative indexes of perfusion and oxidative metabolism from acetate PET indicate a critical threshold beyond which tissue is irreversibly injured. Findings support the use of blood flow as a marker of myocardial viability in chronic postinfarct patients with modestly reduced ejection fractions.

Acetates↗

Use of positron emission tomography (PET) in the assessment of skeletal muscle glucose metabolism.

Non invasive imaging techniques, such as, positronemission tomography (PET), contribute to our present knowledge of glucose metabolism. Besides measurements of net glucose metabolism, PET provides insights into complex processes of intracellular glucose metabolism (i.e., glucose transport and phosphorylation) and is also capable to measure muscular blood flow as a possible determinant of glucose metabolism.

Diabetes Mellitus, Type 2↗

Positron emission tomography and magnetic resonance imaging for cerebral involvement in patients with systemic lupus erythematosus.

Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains difficult to diagnose, particularly since structural abnormalities may not be revealed by magnetic resonance imaging (MRI). Glucose utilisation was measured by positron emission tomography (PET) in 35 SLE patients to detect signs of CNS involvement. The patients were examined by a standardised neurological examination, a battery of tests to evaluate neuropsychological performance and MRI. Antineuronal antibodies were determined to investigate their putative role in CNS involvement in SLE. Twenty patients had distinct neurological (17) and/or psychiatric (3) symptoms. Ten patients had pronounced cognitive impairment. Neurological and cognitive deficits were thus found to be unrelated disorders in SLE. Global glucose utilisation of SLE patients did not differ significantly from that of normal controls, nor were differences found between SLE patients with or without neurological or cognitive abnormalities. On MRI of the brain, the number and size of white matter lesions correlated with the presence of neurological deficits but were unrelated to the severity of cognitive impairment. Within the normal range, lower global glucose utilisation tended towards lower values with increasing number and size of white matter lesions. Patients with lesions larger than 8 mm also showed distinctly increased IgG anticardiolipin antibody titres, whereas measuring antineuronal antibodies did not reveal any relation to the variables investigated. We conclude that the demonstration of CNS lesions by MRI can contribute confirmatory evidence for CNS involvement in SLE, but PET or the presence of antineuronal antibodies adds little if any information beyond that obtained by clinical examination, neuropsychological testing, and MRI.

Adult↗

Dose-related effect of intravenous L-arginine on muscular blood flow of the calf in patients with peripheral vascular disease: a H215O positron emission tomography study.

1. Endothelium-derived nitric oxide (NO) contributes to the regulation of vascular tone and blood pressure. Infusion of L-arginine produces systemic vasodilatation via stimulation of endogenous NO formation. Vasodilatation is accompanied by an increase in peripheral arterial blood flow. However, it is not known whether capillary nutritive blood flow increases as well. The time course and dose-response pattern of this effect remain to be elucidated. 2. Two groups of ten patients with peripheral vascular disease (PVD) received an intravenous infusion of 8 g or 30 g of L-arginine over a period of 40 min. Blood pressure and heart rate were monitored non-invasively. Muscular blood flow (MBF) of the calf was determined at 0, 20, 40, 60, 80 min by positron emission tomography with H215O as flow tracer. Plasma L-arginine and cyclic GMP (cGMP) levels were determined at the same time points. 3. L-arginine induced a dose-related decrease in blood pressure during the infusion period. MBF and plasma cGMP levels during and after the infusion of 8 g of L-arginine did not change significantly. In the patients receiving 30 g of L-arginine, MBF was enhanced significantly from 1.56 +/- 0.14 to 2.09 +/- 0.21 ml min-1 100 ml-1 at 40 min and 2.23 +/- 0.15 ml min-1 100 ml-1 after 80 min (+43.0%). The increase in MBF was paralleled by an increase in plasma cGMP from 4789.8 +/- 392.2 nmol/l at baseline to 9223.2 +/- 1233.6 nmol/l at 40 min. 4. We conclude that intravenous L-arginine enhances nutritive capillary MBF in patients with PVD via the NO-cGMP pathway in a dose-related manner. This effect might be therapeutically beneficial in patients with PVD.

Aged↗

Oxygen-15-water PET assessment of muscular blood flow in peripheral vascular disease.

UNLABELLED: To assess quantitatively regional nutritive muscular blood flow in patients with peripheral vascular disease (PVD), we evaluated the utility of PET with 15O-water. METHODS: Eight healthy volunteers and 16 patients with angiographically proven PVD were studied. Regional blood flow of the calf was measured with 15O-water PET during rest, after intra-arterial infusion of prostaglandin E1 and during ergometry. The studies were quantified using a one tissue compartment model. RESULTS: Normalized mean tracer uptake from 15-60 sec correlated closely (r = 0.98) with absolute blood flow. Scan times longer than 90 sec were required to determine blood flow reliably. The flow values were overestimated by 2% if arterial blood volume was neglected or if the input function delay was corrected globally for parametric imaging. Mean blood flow of calf muscles at rest did not differ significantly between patients (0.017 +/- 0.006 ml/min/ml) and control subjects (0.018 +/- 0.010 ml/min/ml). In PVD patients, blood flow increased by 100% after intra-arterial infusion of PGE1 in the respective leg. In the control subjects, average flow increased by a factor of six during exercise. The increase was more pronounced in the extensor muscles (0.182 +/- 0.031 ml/min/ml) than in flexor muscles (0.121 +/- 0.045 ml/min/ml). Due to the specific type of ergometry, superficial flexors exhibited higher flow values than the profound ones. CONCLUSION: PET with 15O-water enables reliable determination of regional nutritive skeletal muscle blood flow for research and clinical applications in patients with PVD.

Adult↗

A kinetic model for cardiac PET with [1-carbon-11]-acetate.

UNLABELLED: Carbon-11-labeled acetate is a unique tracer for noninvasive assessment of myocardial oxidative metabolism with PET. Because adequate kinetic models have been missing, data evaluation in the past was performed mostly with phenomenological approaches such as mono- or biexponential fitting which cannot account for the influence of finite input duration and blood volume encountered in noninvasive PET investigations. METHODS: To investigate to what extent the current data evaluation schemes are justified, we developed a comprehensive model of [1-11C]-acetate kinetics in the myocardium which incorporates five tissue compartments: free acetate, activated acetate, CO2 precursors, amino acids and CO2. We derived the analytical solution of the model equations which is used for simulations and data fitting. RESULTS: The five-compartment model can reproduce in detail known experimental data. The resulting values of the eight model parameters compare favorably with existing biochemical facts. We have established the relation between parameters of the detailed model and one- and two-compartment models used for the evaluation of PET investigations. CONCLUSION: The kinetics of [1-11C]-acetate are adequately described by a five-compartment model. One- and two-compartment models are sufficient for simultaneous quantitative assessment of myocardial oxidative metabolism and perfusion with [1-11C]-acetate and PET.

Acetates↗

A compartmental model for alveolar clearance of pertechnegas.

UNLABELLED: The washout of an inhaled water soluble radiotracer from the lungs is a measure of alveolar integrity. Data evaluation of 99mTc-DTPA studies were previously performed mainly with monoexponential fitting with or without background subtraction. The introduction of 99mTc-pertechnegas for the assessment of alveolar permeability necessitates the investigation of adequate data evaluation schemes for this radiotracer. METHODS: We developed a three-compartmental model to describe 99mTc-pertechnegas kinetics after inhalation. Monoexponential fitting of the first 5 min was investigated as simplification for clinical use. Different background corrections based on blood samples or representative regions of interest were compared. RESULTS: Correction of intra- and extravascular background by subtraction of calibrated curves, which are derived from blood or background areas, resulted in monoexponential washout curves. Clearance rates based on the three-compartmental model were nearly the same as those derived from a monoexponential fit after blood-activity subtraction (r = 0.96). A monoexponential analysis of the first 5 min without any background correction correlates well with the first component of the biexponential analysis (r = 0.97). CONCLUSION: A dynamic study of more than 45 min allows quantitative determination of the transfer rate of 99mTc-pertechnegas from the alveoli into the blood using compartmental analysis. A simplified monoexponential analysis of the first 5 min allows assessment of lung clearance without any background correction.

Administration, Inhalation↗

Evaluation of the incorporation of bone grafts used in maxillofacial surgery with [18F]fluoride ion and dynamic positron emission tomography.

This study investigates the incorporation of bone grafts used in maxillofacial surgery by means of [18F]fluoride ion and positron emission tomography (PET). It considers patients who received pedicle grafts for mandibular reconstruction or onlay grafts for alveolar ridge augmentation. Dynamic PET images and arterialized venous blood samples were obtained within a 1-h period after i.v. injection of [18F]fluoride. Assuming a three-compartment model and applying multilinear least squares fitting, bone blood flow (K1) and fluoride influx (Kmlf) were determined. Additionally Patlak plot analysis was used to calculate fluoride influx (Kpat). In cervical vertebral bodies as the reference region, mean values for flow of K1 = 0.1162 +/- 0.0396 ml/min/ml and influx of Kmlf = 0.0508 +/- 0.0193 and Kpat = 0.0385 +/- 0.0102 ml/min/ml were found. Essentially these figures are comparable with physiological values in animal and man reported in the literature. Early after surgery a significant increase in flow and influx compared to vertebral bodies was observed in the regions of osteosyntheses between grafts used for reconstruction and recipient bone (K1 = 0.2181, Kmlf = 0.1000 and Kpat = 0.0666 ml/min/ml) and in onlay grafts (K1 = 0.2842, Kmlf = 0.1637 and Kpat = 0.0827 ml/min/ml). At the same time pedicle grafts showed a significant increase in flow but not in influx (K1 = 0.2042, Kmlf = 0.0774 and Kpat = 0.0529 ml/min/ml). Furthermore Kpat was significantly lower in pedicle grafts than in onlay grafts. In follow-up studies a significant decrease in flow occurred in pedicle grafts and the regions of osteosyntheses. Moreover the latter showed a significant decrease in Kmlf as well. It is concluded that [18F(-)] PET depicted increased blood flow and osteoblastic activity in onlay grafts and regions of osteosyntheses, indicating bone repair in the graft and adjacent host bone early after surgery. For the regions of osteosyntheses the decrease in both parameters corresponded to uncomplicated healing. The lack of increased influx, although flow was increased in pedicle grafts, most likely indicates that some necrosis occurred in these grafts despite patency of anastomoses. It may be concluded that [18F(-)] PET provides further insight into the biology of graft incorporation.

Adult↗

[Coronary reserve after orthotopic heart transplantation: quantification with N-13 ammonia and positron emission tomography].

Coronary transplant vasculopathy is known to be associated with an early impairment of endothelium-dependent vasodilatation. In this study the largely endothelium-independent dilator response to dipyridamole was evaluated in 22 patients 36 +/- 17 months after transplantation in relation to their angiographic findings. The dipyridamole coronary reserve was measured by N-13 ammonia and positron emission tomography (PET). Transplant vasculopathy was suspected or evident in 13 of 22 patients by coronary angiography. Coronary reserve was lower in transplant recipients than in normal controls (2.3 +/- 0.9 vs. 4.7 +/- 1.4). Those with a normal angiogram had a near normal minimal coronary resistance (0.3 +/- 0.04 mmHg.min.100 g/ml) and a normalized coronary reserve after correction for the increased resting blood flow (4.8 +/- 0.7). However, in patients with angiographic vasculopathy, coronary reserve was markedly reduced (1.8 +/- 0.7, corrected 2.7 +/- 1.0) and minimal coronary resistance was elevated (0.6 +/- 0.3, p < 0.001). Moreover, regional coronary reserve was homogeneously reduced throughout the myocardium without a clear segmental relationship to angiographic stenoses. After testing of other factors known to influence coronary resistance, our data are compatible with diffuse obstructions of the microvascular bed that are associated with an angiographically visible vasculopathy. The evaluation of coronary reserve by dipyridamole and PET provides a useful extension of angiography in these patients.

Adult↗

Steroid resistant nephrotic syndrome associated with spondyloepiphyseal dysplasia, transient ischemic attacks and lymphopenia.

Focal segmental glomerulosclerosis, nephrotic syndrome and chronic renal failure were associated with spondyloepiphyseal dysplasia, growth failure, lymphopenia and transient ischemic attacks leading to severe neurological symptoms in three children. Two boys and one girl developed the full syndrome at the age of 5, 6 and 10 years. Positron emission tomography revealed perfusion defects of both cerebral and cerebellar arteries. A variant of the disease was found in two other children who had a nephrotic syndrome and terminal renal failure with only mild spondyloepiphyseal dysplasia, impaired growth and a normal cerebral function. It is concluded that there may be a close association between focal segmental glomerulosclerosis and spondyloepiphyseal dysplasias.

Brain↗

Combined spatial and temporal imaging of brain activity during visual selective attention in humans.

Visual-spatial attention is an essential brain function that enables us to select and preferentially process high priority information in the visual fields. Several brain areas have been shown to participate in the control of spatial attention in humans, but little is known about the underlying selection mechanisms. Non-invasive scalp recordings of event-related potentials (e.r.ps) in humans have shown that attended visual stimuli are preferentially selected as early as 80-90 ms after stimulus onset, but current e.r.p. methods do not permit a precise localization of the participating cortical areas. In this study we combined neuroimaging (positron emission tomography) with e.r.p. recording in order to describe both the cortical anatomy and time course of attentional selection processes. Together these methods showed that visual inputs from attended locations receive enhanced processing in the extrastriate cortex (fusiform gyrus) at 80-130 ms after stimulus onset. These findings reinforce early selection models of attention.

Attention↗

Insulin resistance in liver cirrhosis. Positron-emission tomography scan analysis of skeletal muscle glucose metabolism.

BACKGROUND: Insulin resistance and glucose intolerance are a major feature of patients with liver cirrhosis. However, site and mechanism of insulin resistance in cirrhosis are unknown. We investigated insulin-induced glucose metabolism of skeletal muscle by positron-emission tomography to identify possible defects of muscle glucose metabolism in these patients. METHODS: Whole body glucose disposal and oxidation were determined by the combined use of the euglycemic-hyperinsulinemic clamp technique (insulin infusion rate: 1 mU/kg body wt per min) and indirect calorimetry in seven patients with biopsy-proven liver cirrhosis (Child: 1A, 5B, and 1C) and five healthy volunteers. Muscle glucose uptake of the thighs was measured simultaneously by dynamic [18F]fluorodeoxyglucose positron-emission tomography scan. RESULTS: Both whole body and nonoxidative glucose disposal were significantly reduced in patients with liver cirrhosis (by 48%, P < 0.001, and 79%, P < 0.0001, respectively), whereas glucose oxidation and the increase in plasma lactate were normal. Concomitantly, skeletal muscle glucose uptake was reduced by 69% in liver cirrhosis (P < 0.003) and explained 55 or 92% of whole body glucose disposal in cirrhotics and controls, respectively. Analysis of kinetic constants using a three-compartment model further indicated reduced glucose transport (P < 0.05) but unchanged phosphorylation of glucose in patients with liver cirrhosis. CONCLUSIONS: Patients with liver cirrhosis show significant insulin resistance that is characterized by both decreased glucose transport and decreased nonoxidative glucose metabolism in skeletal muscle.

Adult↗

Accurate local blood flow measurements with dynamic PET: fast determination of input function delay and dispersion by multilinear minimization.

Accurate determination of local blood flow in tissue using the Kety-Schmidt one-compartment model for freely diffusible tracers requires knowledge of the true arterial input function in tissue. Because measured input functions are usually delayed and dispersed with respect to true influx, a correction of the experimental input function is necessary. We describe a technique that uses a fast multilinear least-squares minimization procedure to determine simultaneously the dispersion, the blood flow and the partition coefficient as a function of delay. In this approach, a few multilinear fits are sufficient to determine the complete set of parameters necessary to describe the data. Because of the high speed of the procedure, dispersion effects may be taken into account on a pixel-by-pixel basis in calculating parametric images of blood flow and partition coefficient. The described procedure has been used at our institute for about 1 yr in more than 160 investigations and has proven well suited for routine use in a clinical environment.

Blood Flow Velocity↗

Limitations of clearance determination using the single sample distribution volume method. An error analysis on the basis of compartment models.

To investigate the error possibly contained in the single sample distribution volume method for the determination of renal clearance, a mathematical model was applied to describe the effect of changes in distribution volume, clearance, intravascular space, intracompartmental exchange and the time point of blood sampling. The method was found to be valid only under well-defined circumstances (Topt = 45 +/- 5 min, Cl = 390 +/- 50 ml/min, Vd = 16.7 +/- 4 l, alpha = 0.05.V1 ml/min, V1/Vd = 0.5 +/- 0.05) as shown in sample calculations. Two-compartment model-based error calculations demonstrate that this technique implies at best an uncertainty of +/- 10% or more. Whilst it can be used preferably in healthy, normal-weight adults, it is not applicable, without error, under all other circumstances.

Humans↗

Imaging of dialysis-related amyloid (AB-amyloid) deposits with 131I-beta 2-microglobulin.

The diagnosis of dialysis-related amyloid (AB-amyloid) has been based usually on clinical and radiological criteria. Following the discovery that beta 2-microglobulin was the major protein of this amyloid, we isolated and radiolabelled uremic plasma beta 2-microglobulin. After intravenous injection, gamma-camera images of selected joint areas were obtained from 42 patients who were on regular hemodialysis therapy. Positive scans involving the shoulder, hip, knee and carpal regions were found in 13 of 14 patients treated for more than 10 years and 10 of 16 patients treated for 5 to 10 years. Patients treated for less time had negative scans. Specificity was indicated by negative scans in non-amyloid inflammatory lesions in control hemodialysis patients. Up to 48-fold tracer enrichment was detected in excised AB-amyloid containing tissue as compared to amyloid-free tissue. These findings suggest that circulating radiolabelled beta 2-microglobulin is taken up by the amyloid deposits. This method may non-invasively detect tissue infiltrates of amyloid. It may also permit prospective evaluation of the efficacy of prophylactic dialysis strategies which are designed to prevent or delay the onset of this complication of long-term dialysis.

Amyloidosis↗