Search PubMed⌕ Search

Biomedical subjects

M Weckesser

Publications and source records attributed to M Weckesser.

At least 37 records · Page 2Linked to original sources

Sequential scintigraphic strategy for the differentiation of brain tumours.

Both thallium-201 and iodine-123 alpha-methyltyrosine (123I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of 201Tl and 123I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. 201Tl SPET and 123I-IMT SPET were performed [start of 201Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of 123I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked 201Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant 201Tl accumulation [Tl(15')>2.0]; 123I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs. 2.1 vs. 1.8), with metastases showing a high variability in 123I-IMT uptake (range: 0.8-3.6). Using 201Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of 201Tl and 123I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial 201Tl SPET study and an additional 123I-IMT SPET study in the event of positive 201Tl uptake.

Adult↗

Drug-induced changes in cerebral glucose consumption in bifrontal epilepsy.

PURPOSE: Positron emission tomography (PET) using 18F-radiolabeled deoxyglucose (18F-FDG) is a sensitive procedure for detection of epileptogenic foci. Although alterations in glucose consumption are not restricted to the area of seizure generation itself, the magnitude and extent of cerebral metabolic disturbances induced by epileptic discharges can be detected. Despite two decades of epilepsy research using 18F-FDG-PET, little is known about the metabolic changes during therapy of focal epilepsy. We report on a child with frontal epilepsy with severe glucose hypometabolism that was nearly completely normalized during drug therapy. METHODS: Interictal 18F-FDG-PET was performed at the onset of epilepsy and after optimized drug therapy in a 5-year-old boy with behavioral abnormalities and repetitive seizures of frontal origin with bifrontal interictal EEG slowing for 8 weeks. Both scans were anatomically matched; initial and intratherapeutic glucose metabolism were compared. RESULTS: In accordance with the epileptogenic focus as identified by EEG and ictal/interictal perfusion single-photon emission tomography (SPECT), bifrontal hypometabolism was depicted by 18F-FDG-PET. Magnetic resonance imaging (MRI) was unremarkable. After dual-drug therapy (valproate, carbamazepine), the boy became seizure free, and his initial behavioral deficits disappeared. A control PET study after 3 months of therapy showed restored glucose consumption; the frontal EEG slowing was normalized. CONCLUSIONS: This case demonstrates that reduction of glucose metabolism in epileptogenic foci may be a result of reversible neuronal dysfunction that correlates with the electroclinical follow-up.

Anticonvulsants↗

[The role of L-3-I-123-iodine-alpha-methyltyrosine SPECT in cerebral gliomas].

L-3-I-123-iodine-alpha-methyltyrosine (IMT) is a I-123-labelled amino acid which has been used for single photon emission computed tomography (SPECT) of cerebral gliomas for more than a decade. IMT-SPECT is able to detect tumor infiltration independent of disruptions of the blood-brain barrier which is often difficult with computed tomography or magnetic resonance tomography. The method is useful to detect tumor recurrences and helps to distinguish gliomas from non-neoplastic brain masses. IMT-SPECT is thus a valuable tool in the diagnostic evaluation and in therapy planning of patients with cerebral gliomas.

Blood-Brain Barrier↗

Functional imaging of the visual cortex with bold-contrast MRI: hyperventilation decreases signal response.

Hypocapnia due to hyperventilation reduces cerebral blood flow and volume. To investigate the effects of hyperventilation on the regional signal response to visual activation using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI), six volunteers were investigated during visual stimulation under normocapnia and hypocapnia conditions. Hyperventilation significantly decreased in visual cortex the BOLD MRI response to visual stimulation (3.97+/-0.5% [mean ( SD) in normocapnia vs. 0.77+/-0.7% in hypocapnia, P < 0.01]. In three of six subjects, functional signal changes were reduced to noise level. The reduced stimulus response during hyperventilation is probably due to a decreased overshoot in the blood oxygenation response. These results indicate that BOLD-contrast functional MRI is highly sensitive to pCO2 changes.

Adult↗

Kinetics of 3-[(123)I]iodo-l-alpha-methyltyrosine transport in rat C6 glioma cells.

3-[(123)I]Iodo-l-alpha-methyltyrosine ((123)I-IMT) is used for the diagnosis and monitoring of brain tumours by means of single-photon emission tomography (SPET). To date, little has been known about the system for the transport of (123)I-IMT into brain tumour cells. It is assumed that (123)I-IMT is transported by a specific carrier for large, neutral amino acids (L-system). In this study, rat C6 glioma cells were used to characterize the uptake system of (123)I-IMT and to investigate its precise kinetics. The time course of (123)I-IMT uptake into the cells was examined for a range of 1-60 min. (123)I-IMT uptake rates with varying concentrations of (123)I-IMT (2. 5-50 microM) in the medium were quantified to assess the kinetic parameters of (123)I-IMT transport. Furthermore, competition of (123)I-IMT with other amino acids was investigated to identify the distinct transport systems involved in (123)I-IMT uptake. (123)I-IMT uptake into C6 glioma cells was linear for approximately 10 min and reached a steady-state level within 30 min. The analysis of the rate of uptake of (123)I-IMT at different concentrations was concordant with the predominance of a single uptake system. The apparent Michaelis constant (K(m)) of (123)I-IMT was 26.2+/-1.9 microM, and the maximum transport velocity (V(max)) was 35.4+/-1.7 nmol/mg protein per 10 min. 77%+/-10% of (123)I-IMT transport was sodium independent and 23%+/-3% was sodium dependent. Competitive inhibition of (123)I-IMT uptake by 2-aminobicyclo[2.2. 1]heptane-2-carboxylic acid, alpha-(methylamino)isobutyric acid and naturally occurring amino acids revealed a major (123)I-IMT transport via the sodium-independent system L (72%) and a minor uptake via the sodium-dependent system B(0,+) (17%). Our results show that (123)I-IMT transport into C6 glioma cells is principally mediated by the L-system and to a minor extent by the B(0,+)-system. The kinetic parameters of (123)I-IMT uptake are in the range of those of naturally occurring amino acids.

Animals↗

Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer.

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has proven useful in the differentiation of various tumour entities, including breast cancer. In patients with primary breast cancer we performed a 3-h imaging protocol to examine possible improvements in tumour detectability and image contrast. Twenty-nine patients with primary breast cancer with a diameter of >/=2 cm that was demonstrated to be malignant by biopsy or surgery were injected with 370-740 MBq 18F-FDG and scanned in the prone position. Data were acquired 0-40 min, 1.5 h and 3.0 h after injection. After correction for measured attenuation, decay and scatter and iterative reconstruction, standardised uptake values (SUVs) and tumour-to-non-tumour and tumour-to-organ ratios were calculated. Visual analysis was performed using transverse, sagittal and coronal slices as well as 3D reprojection images. Tumour-to-non-tumour and tumour-to-organ ratios were significantly higher for the 3-h images than for the 1.5-h images. SUVs did not increase to the same extent. Lesion detectability was 83% in 1.5-h images compared to 93% in 3-h images. We conclude that tumour contrast in breast cancer is improved by starting the PET acquisition at 3 h p.i. rather than at 1.5 h p.i.

Adult↗

Imaging sympathetic innervation.

The autonomic innervation of the heart modifies most cardiac functions. Especially the heart rate and the force of contraction of myocytes are modulated by the autonomic nervous system. A number of specific neurotransmitters interact with receptors on post- and presynaptic binding sites regulating the complex electromechanical system of the heart. Disturbances at this interaction result in a variety of cardioneuropathies. The clinical manifestations can be mild and may only consist of sporadic arrhythmias without hemodynamic effects. In some cases however the autonomic dysfunction may be severe, e.g. in the acute phase of the Guillain-Barré syndrome and in advanced diabetic neuropathy. At present, the only available techniques to visualise and quantitate disbalanced innervation of the myocardium are scintigraphic modalities as single photon emission tomography (SPECT) and positron emission tomography (PET) with appropriate radiopharmaceuticals. These methods are reviewed with respect to their possible clinical application and to future developments.

Autonomic Nervous System Diseases↗

Iodine-123 alpha-methyl tyrosine single-photon emission tomography of cerebral gliomas: standardised evaluation of tumour uptake and extent.

Single-photon emission tomography (SPET) with the amino acid analogue l-3-[123I]iodo-alpha-methyl tyrosine (IMT) is helpful in the diagnosis and monitoring of cerebral gliomas. Radiolabelled amino acids seem to reflect tumour infiltration more specifically than conventional methods like magnetic resonance imaging and computed tomography. Automatic tumour delineation based on maximal tumour uptake may cause an overestimation of mean tumour uptake and an underestimation of tumour extension in tumours with circumscribed peaks. The aim of this study was to develop a program for tumour delineation and calculation of mean tumour uptake which takes into account the mean background activity and is thus optimised to the problem of tumour definition in IMT SPET. Using the frequency distribution of pixel intensities of the tomograms a program was developed which automatically detects a reference brain region and draws an isocontour region around the tumour taking into account mean brain radioactivity. Tumour area and tumour/brain ratios were calculated. A three-compartment phantom was simulated to test the program. The program was applied to IMT SPET studies of 20 patients with cerebral gliomas and was compared to the results of manual analysis by three different investigators. Activity ratios and chamber extension of the phantom were correctly calculated by the automatic analysis. A method based on image maxima alone failed to determine chamber extension correctly. Manual region of interest analysis in patient studies resulted in a mean inter-observer standard deviation of 8.7% +/ -6.1% (range 2.7% -25.0%). The mean value of the results of the manual analysis showed a significant correlation to the results of the automatic analysis (r = 0.91, P<0. 0001 for the uptake ratio; r = 0.87, P<0.0001 for the tumour area). We conclude that the algorithm proposed simplifies the calculation of uptake ratios and may be used for observer-independent evaluation of IMT SPET studies. Three-dimensional tumour recognition and transfer to co-registered morphological images based on this program may be useful for the planning of surgical and radiation treatment.

Algorithms↗

Influence of acetylcholine on binding of 4-[125I]iododexetimide to muscarinic brain receptors.

The distribution of nicotinic and muscarinic cholinergic receptors in the human brain in vivo has been successfully characterized using radiolabeled tracers and emission tomography. The effect of acetylcholine release into the synaptic cleft on receptor binding of these tracers has not yet been investigated. The present study examined the influence of acetylcholine on binding of 4-[125I]iododexetimide to muscarinic cholinergic receptors of porcine brain synaptosomes in vitro. 4-Iododexetimide is a subtype-unspecific muscarinic receptor antagonist with high affinity. Acetylcholine competed with 4-[125I]iododexetimide in a dose-dependent manner. A concentration of 500 microM acetylcholine inhibited 50% of total specific 4-[125I]iododexetimide binding to synaptosomes when both substances were given simultaneously. An 800 microM acetylcholine solution reduced total specific 4-[125I]iododexetimide binding by about 35%, when acetylcholine was given 60 min after incubation of synaptosomes with 4-[125I]iododexetimide. Variations in the synaptic acetylcholine concentration might influence muscarinic cholinergic receptor imaging in vivo using 4-[123I]iododexetimide. Conversely, 4-[123I]iododexetimide might be an appropriate molecule to investigate alterations of acetylcholine release into the synaptic cleft in vivo using single photon emission computed tomography.

Acetylcholine↗

[Pathogenetic differentiation of the bone superscan using bone marrow scintigraphy].

The case of a 54 year old patient suffering from a prostatic carcinoma is presented. At the time of diagnosis multiple bone metastases were detected by bone scintigraphy. An initial improvement was observed following antiandrogenic therapy. After three years the patient presented with increasing bone pain, which was most prominent in the knee joints. A "superscan" was found in bone scintigraphy with an unusually high uptake in the peripheral skeleton. Bone marrow scinitgraphy showed a nearly complete metastatic displacement of central bone marrow and a peripheral marrow extension as explanation for the bone scan findings.

Androgen Antagonists↗

Effect of partial volume correction on muscarinic cholinergic receptor imaging with single-photon emission tomography in patients with temporal lobe epilepsy.

Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.

Adult↗

Regional dynamic signal changes during controlled hyperventilation assessed with blood oxygen level-dependent functional MR imaging.

PURPOSE: To quantitate the amplitude changes and temporal dynamics of regional functional MR imaging signals during voluntary hyperventilation using blood oxygen level-dependent contrast echo-planar imaging. METHODS: Seven male subjects were studied during voluntary hyperventilation (PetCO2 = 20 mm Hg) regulated by capnometry. Measurements were made on multisection echo-planar MR images obtained with parameters of 1000/66 (repetition time/echo time), flip angle of 30 degrees, and voxel size of 3 x 3 x 5 mm3. Sensitivity of the functional MR imaging signal to changes in PetCO2, time delays in relation to PetCO2 changes, and time constants of functional MR imaging signal changes were assessed on a region-by-region basis. RESULTS: Within 20 seconds of starting hyperventilation, rapid and substantial decreases in the functional MR imaging signal (by as much as 10%) were measured in areas of gray matter, which were significantly greater than the modest changes observed in white matter. Regional-specific effects in areas of the frontal, occipital, and parietooccipital cortex were stronger than in subcortical regions or in the cerebellum. Signal decreases measured with functional MR imaging were significantly delayed with respect to the reduction in PetCO2. Apparent differences between regional time constants did not reach statistical significance. CONCLUSION: Regional and gray-white matter differences in functional MR imaging signal changes during controlled hyperventilation may reflect differences in metabolic activity, vascular regulation, and/or capillary density. When measuring brain activation with functional MR imaging, arterial PCO2 differences due to unregulated respiration may confound interpretation of activation-related functional MR imaging signal changes.

Adult↗