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Biomedical subjects

T Kuwert

Publications and source records attributed to T Kuwert.

At least 19 recordsLinked to original sources
PubMed2006

Tissue distribution of radioiodinated FAUC113: assessment of a pyrazolo(1,5-a) pyridine based dopamine D4 receptor radioligand candidate.

AIM: Disturbances of the D4 receptor subtype have been implicated in the genesis of a broad range of psychiatric disorders. In order to assess the suitability of a radioiodinated analogue of the D4-selective ligand FAUC 113 for tracer studies in vivo, we investigated the in-vivo stability, biodistribution and brain-uptake of 7-(131)I-FAUC 113 in Sprague-Dawley rats. METHODS: Radiolabelling was carried out with high radiochemical yield and specific activity. After intravenous injection, blood and tissue samples, taken at designated time intervals, were collected for analysis. Analyses of metabolites were performed by radio-hplc and radio-tlc. For in-vivo evaluation, sagittal cryo-sections of the rat brain were investigated by in-vitro and ex-vivo autoradiography on a mu-Imager system. RESULTS: 7-(131)I-FAUC 113 was rapidly cleared from blood. Highest uptake was observed in kidney (0.603 +/- 0.047% ID/g, n = 4) and liver (0.357 +/- 0.070% ID/g, n = 4) at 10 min p.i.; 7-(131)I-FAUC 113 displayed rapid uptake (0.21-0.26% ID/g) and fast clearance in various brain regions consistent with the determined logP-value of 2.36 +/- 0.15 (n = 4). In-vivo stability of 7-(131)I-FAUC 113 was confirmed in the frontal cortex (>95%). Ex-vivo autoradiography revealed a frontal cortex-to-cerebellum ratio of 1.57 +/- 0.13 at 10 min p.i. (n = 6). Coinjection with L-750667 could not suppress any putative specific binding of 7-(131)I-FAUC 113. In-vitro autoradiography using authentic 7-iodo-FAUC 113 or L-750667 failed to cause significant displacement of the radioligand. CONCLUSIONS: Radioiodinated FAUC 113 does not allow imaging of D4 receptors in the rat brain in vivo nor in vitro. Further work should aim at the development of selective dopamine D4 radioligands with improved tracer characteristics, such as receptor affinity and subtype selectivity, specific activity or blood-brain barrier permeability.

Animals↗
PubMed2006

Retrospective interactive rigid fusion of (18)F-FDG-PET and CT. Additional diagnostic information in melanoma patients.

AIM: This study investigates whether interactive rigid fusion of routine PET and CT data improves localization, detection and characterization of lesions compared to separate reading. For this purpose, routine PET and CT scans of patients with metastases from malignant melanoma were used. PATIENTS, METHODS: In 34 patients with histologically confirmed malignant melanoma, FDG-PET and spiral CT were performed using clinical standard protocols. For all of these patients, gold standard was available. Clinical and radiological follow-up identified 82 lesions as definitely pathological. Two board-certified nuclear medicine physicians and two board-certified radiologists analyzed PET and CT images independently from each other. For each patient up to 32 anatomical regions (24 lymph node regions, 8 extranodular regions) were systematically classified. Discordant areas were interactively analyzed in manually and rigidly registered images using a commercially available fusion tool. No side-by-side reading was performed. RESULTS: Image fusion disclosed that the evaluation of the PET images alone led to a mislocalization in 26 of 91 focally FDG enhancing lesions. The overall sensitivities of PET, CT, and image fusion were 85, 88, and 94%, respectively; the overall specificities of PET, CT and image fusion were 98, 95 and 100%, respectively. Image fusion exhibited statistically significant higher specificity values as compared with CT. Ten definitely malignant sites were false-negative in CT, but could be detected by PET. On the other hand, twelve metastases were false-negative in PET, but could be detected by CT. These included two lesions, which had a clear correlate on the PET image when the fused images were evaluated. On the whole, registration of the PET and CT images yielded additional diagnostic information in 44% of the definitely malignant lesions. CONCLUSION: Retrospective image fusion of independently obtained PET and CT data is particularly valuable in exactly localizing foci of abnormal FDG uptake and improves the detection of metastases of malignant melanoma.

Adult↗
PubMed2005

Attenuation correction of SPECT images based on separately performed CT: Effect on the measurement of regional uptake values.

AIM: A new software approach uses separately acquired CT images for attenuation correction after retrospective fusion with the SPECT data. This study evaluates the effect of this CT-based attenuation correction on indium-111-pentetreotide-SPECT images. METHODS: Indium-111-pentetreotide-SPECT imaging using a dual-head gamma camera e.cam (Siemens Medical Solutions, Erlangen, Germany) as well as separate spiral computed tomography (CT) was performed in 13 patients. After fusion of SPECT and CT data, the bilinear attenuation coefficients were calculated for each pixel in the CT image volume using their Hounsfield unit values and attenuation-corrected images were reconstructed iteratively (OSEM 2D). Regions of interest (ROIs) were drawn on 24 suspicious foci and background, and target to background ratios were calculated for corrected (TBAC) and uncorrected (TBNAC) images. The shortest distance from the centre of the lesion to the surface of the body (DS) was measured on the corresponding CT slice. Furthermore, ROIs were drawn over the rim and the centre of the liver. Ratios of hepatic count rates for corrected (LRAC) and uncorrected (LRNAC) images were also compared. RESULTS: In lesions located more centrally, TBAC was up to 52% higher, whereas in peripherally located lesions, TBAC was up to 63% lower than TBNAC. The TBAC/TBNAC quotient was linearly correlated with DS. In the liver, attenuation correction resulted in a 35% increase of LRAC compared with LRNAC. CONCLUSIONS: Attenuation correction of SPECT images performed by separately acquired CT data is quick and simple. It improves the contrast between target and background for lesions located more centrally in the body and improves homogeneity of the visualisation of tracer uptake in the liver.

Adult↗
PubMed2005

[Anatomical accuracy of lesion localization. Retrospective interactive rigid image registration between 18F-FDG-PET and X-ray CT].

UNLABELLED: The aim of this study was to evaluate the anatomical accuracy and reproducibility of retrospective interactive rigid image registration (RIR) between routinely archived X-ray computer tomography (CT) and positron emission tomography performed with 18F-deoxyglucose (FDG-PET) in oncological patients. METHODS: Two observers registered PET and CT data obtained in 37 patients using a commercially available image fusion tool. RIR was performed separately for the thorax and the abdomen using physiological FDG uptake in several organs as a reference. One observer performed the procedure twice (O1a and O1b), another person once (O2). For 94 malignant lesions, clearly visible in CT and PET, the signed and absolute distances between their representation on PET and CT were measured in X-, Y-, and Z-direction with reference to a coordinate system centered in the CT representation of each lesion (X-, Y-, Z-distances). RESULTS: The mean differences of the signed and absolute distances between O1a, O1b, and O2 did not exceed 3 mm in any dimension. The absolute X-, Y-, and Z-distances ranged between 0.57 +/- 0.58 cm for O1a (X-direction) and 1.12 +/- 1.28 cm for O2 (Z-direction). When averaging the absolute distances measured by O1a, O1b, and O2, the percentage of lesions misregistered by less than 1.5 cm was 91% for the X-, 88% for the Y-, and 77% for the Z-direction. The larger error of fusion determined for the remaining lesions was caused by non-rigid body transformations due to differences in breathing, arm position, or bowel movements between the two examinations. Mixed effects analysis of the signed and absolute X-, Y-, and Z-distances disclosed a significantly greater misalignment in the thorax than in the abdomen as well as axially than transaxially. CONCLUSION: The anatomical inaccuracy of RIR can be expected to be <1.5 cm for the majority of neoplastic foci. Errors of alignment are bigger in the thorax and in Z-direction, due to non-rigid body transformations caused, e.g., by breathing.

Fluorodeoxyglucose F18↗
PubMed2004

Predictive value of impaired uterine transport function assessed by negative hysterosalpingoscintigraphy (HSSG).

BACKGROUND: Hysterosalpingoscintigraphy (HSSG) has given insight into the dynamics of rapid sperm transport inside the female genital tract. RESULTS: While there is an increase of an ipsilateral transport on the side bearing the dominant follicle in 70% of the subjects in the periovulatory phase, 15% of the patients do not demonstrate transport to the fallopian tubes (negative HSSG). In these patients the pregnancy rate achieved spontaneously or by intrauterine insemination is significantly reduced compared to the patients who showed an intact transport mechanism confirmed by positive HSSG. On the other hand, by means of assisted reproductive techniques (ART), pregnancy rates were higher in the group of patients showing negative HSSG (P < 0.0005). CONCLUSIONS: Our data clearly indicate that HSSG is a helpful method to evaluate the integrity of the utero-tubal transport mechanism. As pregnancy rates remain low in patients with negative HSSG, this result should be considered as an indication for IVF-treatment even in patients with patent fallopian tubes and normozoospermia of the partner.

Fallopian Tube Patency Tests↗
PubMed2004

Influence of TSH on uptake of [18F]fluorodeoxyglucose in human thyroid cells in vitro.

Recent clinical evidence suggests that positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is more accurate in detecting thyroid carcinomatous tissue at high than at low TSH levels. The aim of this study was to determine the influence of TSH on FDG uptake in human thyroid cells in vitro. Monolayers of human thyroid tissue were cultured after mechanical disintegration and enzymatic digestion of samples from patients undergoing surgery for nodular goitre. The purity of thyroid cell preparations was ascertained by immunohistochemical staining for the epithelial antigen KL-1, and their viability by measuring the synthesis of thyroglobulin in vitro. The cells were incubated with 0.8-1.5 MBq FDG/ml uptake medium for 1 h. FDG uptake in thyroid cells was quantified as percent of whole FDG activity per well (% ID) or as % ID in relation to total protein mass. This experimental protocol was subsequently varied to study the effect of incubation time, glucose dependency and TSH. Furthermore, radio-thin layer chromatography was used to identify intracellular FDG metabolites. FDG accumulated in the thyroid cells linearly with time, doubling roughly every 20 min. Uptake was competitively inhibited by unlabelled glucose and decreased to approximately 70% at 100 mg/dl glucose compared to the value measured in glucose-free medium. FDG was intracellularly trapped as FDG-6 phosphate and FDG-1,6-diphosphate. TSH significantly increased FDG uptake in vitro in a time- and concentration-dependent manner: Cells cultured at a TSH concentration of 50 micro U/ ml doubled FDG uptake compared to TSH-free conditions, and uptake after 72 h of TSH pre-incubation was approximately 300% of that without TSH pre-incubation. TSH stimulates FDG uptake by benign thyroid cells in a time- and concentration-dependent manner. This supports the clinical evidence that in well-differentiated thyroid carcinomas, most of which are still TSH-sensitive, FDG-PET is more accurate at high levels of TSH.

Cell Survival↗
PubMed2004

TSH-receptor autoantibodies - differentiation of hyperthyroidism between Graves' disease and toxic multinodular goitre.

Previous studies indicate pre-existing subclinical Graves' disease in many patients with the scintigraphic diagnosis of toxic multinodular goitre type A, equivalent to the in Germany so-called disseminated thyroid autonomy. Furthermore, after radioiodine treatment an increase or the induction of TSH-receptor antibodies (TRAb) in patients with Graves' disease or toxic multinodular goitre has been repeatedly reported. The distinction between both hyperthyroid conditions, Graves' disease and toxic multinodular goitre type A, depends on the diagnostic power of the TSH-receptor antibody determination. Bioassays using CHO cell lines expressing the hTSH-receptor or a new TBII assay based on competitive binding to recombinant human TSH-receptor showed a higher sensitivity for the detection of TSH-receptor antibodies in patients with Graves' disease than previous assays using solubilized porcine epithelial cell membranes. In up to 50 % of patients with toxic multinodular goitre A without antithyroid drug pretreatment TSH-receptor antibodies were detectable with a high correlation between thyroid-stimulating antibodies in the bioassay and the h-TBII assay. Moreover, in a recent study the development of TSH-receptor antibodies after radioiodine treatment was detectable in 36 % of patients with toxic multinodular goitre type A, whereas TSH-receptor antibodies were not detectable in patients with toxic multinodular goitre type B or in patients with toxic adenoma. In conclusion, thyroid-stimulating antibodies in a bioassay or TSH-receptor antibodies detected with the h-TBII assay have the highest diagnostic power to differentiate Graves' disease from toxic multinodular goitre. Because of its less cumbersome assay technique the h-TBII should be performed in all patients with hyperthyroidism to differentiate Graves' disease from non-autoimmune hyperthyroidism such as toxic multinodular goitre to select the appropriate therapy for these patients.

Autoantibodies↗
PubMed2003

Determination of velocity of tubar transport with dynamic hysterosalpingoscintigraphy.

Transport of 99mTc labelled albumin macroaggregates (MAA) can be used as a substitute for assessing transport of spermatozoa within the female genital tract. As yet, the velocity of tubar MAA transport has not been systematically studied in a large group. Dynamic hysterosalpingoscintigraphy (HSS) was performed after intrauterine instillation of 10-20 MBq 99mTc-MAA in 88 pre-ovulatory women suffering from infertility. They had to have anatomical patency of both tubes and at least one enlarged follicle. The direction and the latency of transport were evaluated. Forty-four per cent of patients exhibited MAA transport only to the dominant follicle, 31% to both ovaries and 16% to the contralateral ovary. In 9% no transport was visible. Fifty per cent of all patients studied exhibited MAA transport to the dominant follicle within 30 s, 75% within 20 min. Transport velocity in women having bilateral or ipsilateral transport did not differ significantly. There was no significant correlation between the size of the follicle and transport velocity. We conclude that in the majority of cases MAA transport occurs within 30 s after instillation. The variation in transport time between 30 s and 20 min suggests that dynamic scintigraphy is, in principle, better suited to a refined analysis of tubar function than static HSS.

Adult↗
PubMed2003

[Bone scintigraphy and clinical outcome in rheumatoid gonarthritis].

AIM: For evaluation of the effect of radiosynoviorthesis (RSO) on the early and delayed uptake of (99m)Tc-biphosphonates and its relation to clinical outcome we studied these variables before and after radiosynoviorthesis performed on 41 knees affected by rheumatoid arthritis. METHOD: Thirty-seven patients with rheumatoid gonarthritis were treated by intraarticular injection with 185 MBq yttrium-90 citrate. In four of them both knees were treated so that 41 therapies were evaluated. On the average 35 days before and 120 days after radiosynoviorthesis, the early and delayed uptake of (99m)Tc-diphosphonate (DPD) was measured with a planar gamma camera. Early and late DPD uptake was quantified as a ratio between count values derived from rectangular ROIs placed on the knee treated and on the ipsilateral thigh. The severity of clinical symptoms was assessed on two 3-point rating scales averaged. RESULTS: 30 of the 41 cases favorably responded to radiosynoviorthesis. There was a significant correlation between clinical outcome and pretherapeutic early DPD uptake (EDU) (p<0.05), but not between outcome and pretherapeutic late DPD uptake (DDU). In the whole group, EDU decreased in approximately 76% of cases after therapy (p<0.05), DDU in 54% (p>0.05). In 25 of the 30 responders EDU decreased; EDU increased or remained constant in five of the eleven non-responders. The correlation between outcome and the difference in EDU was significant (r = 0.344; p<0.05). There was no such significant relationship between the difference between pre- and posttherapeutic DDU and clinical course. CONCLUSION: Three-phase bone scintigraphy may contribute to predict and assess the success of radiosynovior-thesis in rheumatoid arthritis of the knee joint.

Adult↗
PubMed2003

[Time consumption and quality of an automated fusion tool for SPECT and MRI images of the brain].

AIM: Although the fusion of images from different modalities may improve diagnostic accuracy, it is rarely used in clinical routine work due to logistic problems. Therefore we evaluated performance and time needed for fusing MRI and SPECT images using a semiautomated dedicated software. PATIENTS, MATERIAL AND METHOD: In 32 patients regional cerebral blood flow was measured using (99m)Tc ethylcystein dimer (ECD) and the three-headed SPECT camera MultiSPECT 3. MRI scans of the brain were performed using either a 0,2 T Open or a 1,5 T Sonata. Twelve of the MRI data sets were acquired using a 3D-T1w MPRAGE sequence, 20 with a 2D acquisition technique and different echo sequences. Image fusion was performed on a Syngo workstation using an entropy minimizing algorithm by an experienced user of the software. The fusion results were classified. We measured the time needed for the automated fusion procedure and in case of need that for manual realignment after automated, but insufficient fusion. RESULTS: The mean time of the automated fusion procedure was 123 s. It was for the 2D significantly shorter than for the 3D MRI datasets. For four of the 2D data sets and two of the 3D data sets an optimal fit was reached using the automated approach. The remaining 26 data sets required manual correction. The sum of the time required for automated fusion and that needed for manual correction averaged 320 s (50-886 s). CONCLUSION: The fusion of 3D MRI data sets lasted significantly longer than that of the 2D MRI data. The automated fusion tool delivered in 20% an optimal fit, in 80% manual correction was necessary. Nevertheless, each of the 32 SPECT data sets could be merged in less than 15 min with the corresponding MRI data, which seems acceptable for clinical routine use.

Automation↗
PubMed2001

Temporal hypometabolism at the onset of cryptogenic temporal lobe epilepsy.

Most patients with intractable temporal lobe epilepsy (TLE) exhibit temporal glucose hypometabolism. The reasons for the development of this abnormality are as yet unclear. The current notion is that an initial injury causes seizures, which in turn give rise to hypometabolism. The aim of this study was to assess whether temporal reductions in glucose metabolism in non-lesional TLE are the result of repeated seizures or whether hypometabolism represents an initial disturbance at the onset of disease. Glucose consumption was assessed with fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in 62 patients with cryptogenic non-refractory TLE in different stages of disease. Twelve subjects without neurological illness served as controls. Patients with onset of epilepsy at least 3 years prior to the PET scan were defined as having chronic TLE. Using this criterion, the whole patient cohort included 27 patients with de novo TLE and 35 patients with chronic TLE. The groups were matched for age and sex. The appearance of high-resolution magnetic resonance images of the brain was unremarkable in all patients. In the total cohort, number, duration and frequency of seizures had a significant relation to the magnitude of hypometabolism. Temporal hypometabolism was exhibited by 26 of the 62 patients (42%), including 8 out of 27 (30%) with newly diagnosed TLE and 18 out of 35 (51%) with chronic TLE. The disturbances were more extensive and more severe in patients with chronic TLE. It is concluded that temporal hypometabolism may already be present at the onset of TLE, but is less frequent and less severe in newly diagnosed than in chronic TLE. The metabolic disturbance correlates with the number of seizures. These findings suggest that an initial dysfunction is present in a considerable number of patients and that hypometabolism is worsened by continuing epileptic activity.

Adolescent↗
PubMed2001

Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy--lomanzenil-binding in de-novo TLE.

PURPOSE: Epileptogenic foci exhibit disturbed function at the level of the benzodiazepine receptor. The aim of our study was to investigate the incidence of focal reductions of temporal benzodiazepine receptor binding (BRB) as assessed by scintigraphy with 123I-iomazenil in patients with denovo temporal lobe epilepsy (TLE). METHODS: Forty adult patients (age: 34+/-12 years) with cryptogenic denovo TLE underwent scintigraphy with 123I-iomazenil. In all patients, symptomatic epilepsy was excluded by clinical investigation and MRI. The median duration of TLE was seven months, and the patients had a median of three documented seizures in their history of disease. BRB was quantified in four temporal regions covering the whole temporal lobe. Temporal asymmetry values (ASY) were compared with data determined in 13 age-matched controls yielding Z-scores for global and regional temporal BRB. RESULTS: A significant reduction of temporal BRB was found in 19 of the 40 patients (48 %), mainly in mesial temporal regions; temporal BRB asymmetries were also found in patients with a short history of seizures and low seizure frequency (< or = 1 year; n = 32, 13/32 (41 %)). Only in the entire cohort did the magnitude of temporal reduction of BRB correlate with the duration of TLE as well as with the number of previous partial seizures (r = 0.40 and r = 0.36; p < 0.03, respectively). CONCLUSIONS: Foci of decreased BRB can already be detected at the onset of TLE; their magnitude is related to ongoing epileptic activity.

Adolescent↗
PubMed2001

Interictal cardiac autonomic dysfunction in temporal lobe epilepsy demonstrated by [(123)I]metaiodobenzylguanidine-SPECT.

We studied the post-ganglionic cardiac sympathetic innervation in patients with chronic temporal lobe epilepsy (TLE) by means of [(123)I]metaiodobenzylguanidine-single photon computed tomography (MIBG-SPECT) and evaluated the effects of carbamazepine on cardiac sympathetic innervation. TLE is frequently associated with dysfunction of the autonomic nervous system. Autonomic dysregulation might contribute to unexplained sudden death in epilepsy. Anticonvulsive medication, particularly with carbamazepine, might also influence autonomic cardiovascular modulation. MIBG-SPECT allows the quantification of post-ganglionic cardiac sympathetic innervation, whereas measuring the variability of the heart rate provides only functional parameters of autonomic modulation. Antiepileptic drugs, especially carbamazepine (CBZ), can affect cardiovascular modulation. We determined the index of cardiac MIBG uptake (heart/mediastinum ratio) and heart rate variability (HRV) using time and frequency domain parameters of sympathetic and parasympathetic modulation in 12 women and 10 men (median age 34.5 years) with a history of TLE for 7-41 years (median 20 years). Myocardial perfusion scintigrams were examined to rule out deficiencies of MIBG uptake due to myocardial ischaemia. To assess the possible effects of CBZ on autonomic function, we compared MIBG uptake and HRV in 11 patients who had taken CBZ and 11 patients who had not taken CBZ, and in 16 healthy controls. In order to identify MIBG uptake defects due to myocardial ischaemia, all patients had a perfusion scintigram. Cardiac MIBG uptake was significantly less in the TLE patients (1.75) than in the controls (2.14; P = 0.001), but did not differ between subgroups with and without CBZ treatment. The perfusion scintigram was normal in all patients. Time domain analysis of HRV parameters suggested the predominance of parasympathetic cardiac activity in the TLE patients, but less parasympathetic modulation in the patients treated with CBZ than in those not treated with CBZ (P < 0.05), whereas frequency domain parameters showed no significant difference between the subgroups of patients or between patients and controls. MIBG-SPECT demonstrates altered post-ganglionic cardiac sympathetic innervation. This dysfunction might carry an increased risk of cardiac abnormalities.

3-Iodobenzylguanidine↗
PubMed2000

Differentiation of Parkinson's disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT.

BACKGROUND: Differential diagnosis between idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA) is often difficult in early disease stages. Since MSA is misdiagnosed as PD in more than 20% of the early stages, there is need for methods refining the differentiation of the two disease entities. In PD postganglionic involvement of the autonomic nervous system (ANS) predominates whereas in MSA the ANS is mainly affected in its preganglionic structures. The functional integrity of postganglionic cardiac sympathetic neurons can be investigated using I-123-metaiodobenzylguanidine-single photon emission computed tomography (MIBG-SPECT). OBJECTIVES: We investigated whether I-123-MIBG-SPECT allows to differentiate between early stages of PD and MSA in patients not yet requiring L-dopa therapy. METHODS: Thirty patients (10 PD and 20 MSA patients) underwent MIBG-SPECT and evaluation of heart rate variability (HRV). Patients on any medication interfering with MIBG-accumulation were excluded from the study. Cardiac perfusion was evaluated by myocardial scintigraphy. RESULTS: The median cardiac MIBG uptake was significantly decreased in PD as well as MSA patients compared to controls (P<0.001). However, in the PD group MIBG uptake was significantly lower than in MSA (P=0.03). Even in PD patients without clinical signs of autonomic failure, MIBG uptake was significantly lower than in MSA patients (P=0.03). Analysis of heart rate parameters did not differentiate between PD and MSA patients. The median coefficient of variation was significantly smaller in PD and MSA patients compared to control subjects. CONCLUSIONS: Our study shows that MIBG-SPECT identifies autonomic cardiac dysfunction in very early stages of both, PD and MSA. More importantly, the technique facilitates differentiation of MSA and PD in the early stages. The different pathology with prominent peripheral, postganglionic sympathetic dysfunction in PD and primarily central and preganglionic lesions in MSA accounts for a lower MIBG uptake in PD compared to MSA patients.

Adult↗