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Biomedical subjects

P Bartenstein

Publications and source records attributed to P Bartenstein.

At least 19 recordsLinked to original sources

Positron emission tomography reveals correlations between brain metabolism and mood changes in hyperthyroidism.

CONTEXT: Hyperthyroidism is frequently associated with emotional distress. The underlying cerebral processes of the endocrine-induced mood changes are unclear. OBJECTIVE: The objective of this study was to investigate, for the first time, the neuronal correlates of thyrotoxicosis-associated psychic symptoms using positron emission tomography (PET). DESIGN: The study was designed as a cross-sectional trial. SETTING: The study was performed at joint nuclear medicine and thyroid clinics. PATIENTS: Twelve patients with untreated Graves' hyperthyroidism were evaluated. METHODS: Levels of emotional distress were self-rated by means of the Hospital Anxiety and Depression Scale. Both patients and 20 age- and gender-matched euthyroid controls underwent a brain fluorodeoxyglucose PET scan. Subsequently, the functional relationship between brain metabolism and the psychometric scores was analyzed. RESULTS: Compared with controls and visualized by fluorodeoxyglucose PET, hyperthyroid patients showed a decreased (P < 0.0001) glucose metabolism in the limbic system (uncus and inferior temporal gyrus). Activation foci in the posterior cingulate and in the inferior parietal lobe were correlated with both anxiety and depression scales (P < 0.001). Compared with patients with normal anxiety levels, those with increased anxiety yielded an enhanced glucose metabolism (P < 0.001) in the bilateral sensory association cortex. Serum free T3/free T4 levels negatively correlated with regional glucose metabolism in the medial posterior cingulate. CONCLUSIONS: Thyrotoxicosis and associated psychic symptoms are correlated to regional metabolic changes in the main structures of the limbic/paralimbic system.

Adult↗

Resting state glucose utilization and the CERAD cognitive battery in patients with Alzheimer's disease.

The present study examined the cortical functional representation of neuropsychological domains in Alzheimer's disease (AD) using positron emission tomography (PET) and the neuropsychological assessment battery of the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Thirty patients with clinical probable AD and 10 elderly healthy controls underwent (18)FDG brain PET imaging during a resting state. Correlations between metabolic values and cognitive measures were determined using a region of interest analysis with NEUROSTAT (University of Michigan, USA) and a voxel-based analysis with SPM96 (Wellcome Department, London, UK). Specific correlations were seen between measures of episodic memory, verbal fluency and naming and left hemispheric temporal and prefrontal metabolism. Drawing was correlated with metabolism in left prefrontal and left inferior parietal regions. The presented data support the use of metabolic-cognitive correlations to demonstrate the neuronal substrates of cognitive impairment in AD. Subtests of the CERAD battery give a good representation of left, but not of right hemisphere function in AD.

Aged↗

FDG-PET in the initial staging of squamous cell oesophageal carcinoma.

UNLABELLED: Squamous cell oesophageal carcinoma is the most common carcinoma of the oesophagus worldwide. The tumour stage as most important prognostic factor determines the clinical management. AIM: of this study was to evaluate the value of FDG-PET 1. in imaging the primary tumour and 2. in N- and M-staging of squamous cell oesophageal carcinoma. PATIENTS, METHODS: In 20 patients with histological proven squamous cell carcinoma of the upper and middle oesophagus, FDG-PET was performed in standard technique prior to therapy. FDG uptake in the primary was determined by calculation of the SUVmax. NM-staging due to PET findings was performed as designated by the AJCC/UICC group classification and was compared with pathological and clinically based staging. Sensitivities, specificities and accuracies were calculated. RESULTS: In 19 of 20 patients, primary squamous cell oesopohageal carcinoma was detected by FDG-PET findings with a maximum SUV of 12.5 (mean) +/- 5.1 (median 11.5; range 4.8-23.8). One carcinoma in situ was missed. The sensitivity of FDG-PET in imaging the primary tumour was 96%. The sensitivities, specificities and accuracies were 20%, 100%, 58% for N-staging, and 60%, 86% and 93% for M-staging. PET findings caused changes of therapy in 5% (1 patient). CONCLUSIONS: FDG-PET was excellent in imaging the primary of squamous cell oesophageal carcinoma in stage T1-T4 and was efficient in M-staging. The low sensitivity in N-staging is of inferior clinical importance. The efficacy of FDG-PET seems to be not significantly be influenced by the histological subtype of oesophageal carcinoma.

Aged↗

Association between cognitive performance and cortical glucose metabolism in patients with mild Alzheimer's disease.

BACKGROUND: Neuronal and synaptic function in Alzheimer's disease (AD) is measured in vivo by glucose metabolism using positron emission tomography (PET). OBJECTIVE: We hypothesized that neuronal activation as measured by PET is a more sensitive index of neuronal dysfunction than activity during rest. We investigated if the correlations between dementia severity as measured with the Mini Mental State Examination (MMSE) and glucose metabolism are an artifact of brain atrophy. METHOD: Glucose metabolism was measured using [18F]fluorodeoxyglucose PET during rest and activation due to audiovisual stimulation in 13 mild to moderate AD patients (MMSE score > or = 17). PET data were corrected for brain atrophy. RESULTS: In the rest condition, glucose metabolism was correlated with the MMSE score primarily within the posterior cingulate and parietal lobes. For the activation condition, additional correlations were within the primary and association audiovisual areas. Most local maxima remained significant after correcting for brain atrophy. CONCLUSION: PET activity measured during audiovisual stimulation was more sensitive to functional alterations in glucose metabolism in AD patients compared to the resting PET. The association between glucose metabolism and MMSE score was not dependent on brain atrophy.

Aged↗

Demonstration of pulmonary beta2-adrenergic receptor binding in vivo with [18F]fluoroethyl-fenoterol in a guinea pig model.

PURPOSE: The new beta2 radioligand (R,R)(S,S) 5-(2-(2-[4-(2-[18F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol ([18F]FE-fenoterol; [18F]FEFE), a fluoroethylated derivative of racemic fenoterol, was evaluated in vivo and ex vivo using a guinea pig model. METHODS: Dynamic PET studies over 60 min with [(18)F]FEFE were performed in nine Hartley guinea pigs in which a baseline (group 1, n=3), a predose (group 2, n=3; 2 mg/kg fenoterol 5 min prior to injection of [18F]FEFE) or a displacement study (group 3, n=3; 2 mg/kg fenoterol 5 min post injection of [18F]FEFE) was conducted. RESULTS: In all animal groups, the lungs could be visualised and semi-quantified separately by calculating uptake ratios to non-specific binding in the neck area. Premedication with non-radioactive fenoterol and displacement tests showed significant reduction of lung uptake, by 94% and 76%, respectively. CONCLUSION: These data demonstrate specific binding of the new radioligand to the pulmonary beta2-receptors in accordance with ex vivo measurements. Therefore, [18F]FEFE seems to be suitable for the in vivo visualisation and quantification of the pulmonary beta2-receptor binding in this animal model.

Animals↗

Thalamic infarctions cause side-specific suppression of vestibular cortex activations.

H2O15-PET was performed during caloric vestibular stimulation of the right and left external ears in eight right-handed patients with acute unilateral infarctions or haemorrhages of the posterolateral thalamus (four right, four left). The posterolateral thalamus is the relay station for ipsi- and contralateral ascending vestibular input to the multiple multisensory vestibular cortex areas. The aim of this study was to evaluate the differential effects of unilateral vestibular thalamic lesions on thalamo-cortical projections, right hemispheric dominance and reciprocal inhibitory visual-vestibular interaction, as well as perceptual and ocular motor consequences during caloric irrigation. The major findings of the group analyses of the patients with right-sided and those with left-sided lesions were as follows: (i) activation of the multisensory vestibular temporo-parietal cortex was significantly reduced in the hemisphere ipsilateral to the thalamic lesion when the ipsilesional or contralesional ear was stimulated; (ii) activation of multisensory vestibular cortex areas of the hemisphere contralateral to the irrigated ipsilesional ear was also diminished; and (iii) the right hemispheric dominance in right-handers described above was preserved in those with right and left thalamic lesions. Simultaneous deactivations were often restricted to only one hemisphere--the one contralateral to the stimulation and contralateral to the vestibular cortex areas activated. There was, however, one area in the inferior insula which was also activated by either right or left ear stimulation in the hemisphere ipsilateral to the lesion. This supports the assumption that there is a bilateral direct ascending vestibular projection from the vestibular nuclei to the inferior part of the insula, which bypasses the posterolateral thalamus and is stronger in the right hemisphere. The cortical asymmetry of the pattern of activation during horizontal semicircular canal stimulation by calorics was not associated with a significant direction-specific asymmetry of caloric nystagmus or perceived body motion. Thus, the data demonstrate the functional importance of the posterolateral thalamus as a unique relay station for vestibular input to the cortex, of the dominance of the right hemisphere in right-handedness, and of ipsilateral ascending pathways. Furthermore, the normal interaction between the two sensory systems--the vestibular and the visual--appears to be impaired.

Adult↗

The unpleasantness of tonic pain is encoded by the insular cortex.

OBJECTIVE: Muscle pain differs from skin pain with respect to quality, accuracy of localization, and unpleasantness. This study was conducted to identify the brain regions associated with the affective-motivational component of tonic skin and muscle pain. METHODS: Forty healthy volunteers were investigated in three groups with different F-18 fluorodeoxyglucose PET activation scans. A verbal rating scale (VRS) was used to quantify pain intensity and unpleasantness. One group was investigated during painful infusion of an acidified phosphate buffer (pH 5.2) into either muscle or skin for 30 minutes. Muscle and skin infusions were adjusted to achieve pain intensity rating of VRS = 40. The second group received sham stimulation of muscle and skin by infusion of non-acidified phosphate buffer (pH 7.3 to 7.4, pain intensity = 0). The third group underwent only one PET scan without sensory stimulation. RESULTS: Unpleasantness ratings were higher (VRS 38.3 vs 25.5) during IM compared to intracutaneous stimulation, despite the same pain intensity (VRS = 40). Sham stimulation revealed no pain or unpleasantness. Regional cerebral glucose metabolism during sham stimulation showed similar findings for intracutaneous and IM infusions with significant activations of the bilateral anterior cingulate, bilateral frontal (premotor) cortex, and the ipsilateral parietal operculum. The comparison of pain vs sham stimulation revealed activations of the bilateral insula for IM but not intracutaneous stimulation. The unpleasantness perception in skin and muscle stimulation was positively correlated to the bilateral insular metabolism. CONCLUSION: The data suggest that the insula represents one main structure where the unpleasantness of tonic pain perception is encoded.

Acids↗

In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans.

Pancreatic islet cell mass (PICM) is a major determinant of the insulin secretory capacity in humans. Currently, the only method for accurate assessment of the PICM is an autopsy study. Thus, development of a technique allowing the non-invasive quantification of PICM is of great interest. The aim of this study was to develop such a non-invasive technique featuring novel fluorine- and (99m)Tc-labelled glibenclamide derivatives. Despite the structural modifications necessary to introduce fluorine into the glibenclamide molecule, all derivatives retained insulin stimulating capacity as well as high affinity binding to human SUR1 when compared to the original glibenclamide. Contrastingly, the lipophilicity of the fluorine-labelled derivatives was altered depending on the particular modification. In the human PET-study a constant but weak radioactive signal could be detected in the pancreas using a fluorine-labelled glibenclamide derivative. However, a reliable assessment and visualisation of the PICM could not be obtained. It can be assumed that the high uptake of the fluorine-labelled tracer e.g. into the the liver and the high plasma protein binding leads to a relatively low signal-to-noise ratio. In case of the presented fluorine-labelled glibenclamide based compounds this could be the result of their invariably high lipophilicity. The development of a (99 m)Tc-labelled glibenclamide derivative with a lower lipophilicity and differing in vivo behaviour, glibenclamide based compounds for non-invasive imaging of the pancreatic islet cell mass may be possible.

ATP-Binding Cassette Transporters↗

[Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome: conceptual chances].

The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

Humans↗

Preserved visual-vestibular interaction in patients with bilateral vestibular failure.

BACKGROUND: During caloric vestibular stimulation, subjects showed bilateral activation of the vestibular cortex in the posterior insula and retroinsular region as well as concurrent deactivation of visual cortex areas bilaterally. This finding was the basis for the concept of a reciprocal inhibitory interaction between the vestibular and the visual systems. OBJECTIVE: To analyze the modulations of this activation and deactivation pattern in patients with loss of vestibular input, that is, in patients with bilateral vestibular failure (BVF). METHODS: Modulations of regional cerebral blood flow (rCBF) in PET were measured in nine patients with BVF and compared with those in healthy volunteers using statistical group as well as single-subject analyses (Statistical Parametric Mapping 96b). RESULTS: The group analysis of the BVF patients showed only one small region of activation in the posterior insula contralateral to the stimulated ear, whereas the other areas correlating with vestibular, autonomic, and ocular motor function were not activated. Furthermore, the concurrent rCBF decreases of the primary visual cortex seen in healthy volunteers were not found in the patients. These decreases seem to be dependent on an intact vestibular input with concurrent vestibular nystagmus. CONCLUSIONS: The results are compatible with the concept of a reciprocal inhibitory sensorisensory interaction between the vestibular and visual systems that normally act together for orientation in space and perception of motion. This interaction appears to be preserved in the patients at a significantly lower level, that is, with less activation and less deactivation.

Adult↗

[PET in neuroscience: dopaminergic, GABA/benzodiazepine, and opiate system].

This article gives an overview on radiotracer imaging with positron emission tomography (PET) in measuring various aspects of neurotransmission. The review focuses on the dopaminergic system, the GABA/benzodiazepine system, and the opiate system. Besides dealing with the current clinical applications for brain PET studies with specific radiopharmaceuticals this article outlines an idea on potential future developments for the use of these methods in basic neuroscience.

Animals↗

[Guideline for therapy of malignant thyroid tumours: pleading for an actualization].

Total (or near total) thyroidectomy (TE) followed by radioiodine ((131)I) ablation (RIA) of residual thyroid tissue is considered to be the ideal treatment for differentiated thyroid carcinoma. However, the actual guideline of the DGN (German Society of Nuclear Medicine) recommends for the so-called papillary micro-carcinoma of the thyroid (PMC) no further therapeutic strategy (no complete TE, no (131)I-ablation of the remaining lobe). PMC has been defined as papillary carcinoma measuring 1 cm (T1) in maximal diameter according to the World Health Organization classification system for thyroid tumours (1988). The new WHO-classification (starting in 2003) defines the T1-tumour measuring 2 cm in maximal diameter. The authors demand a new, modern guideline, following the new WHO classification. This includes, that despite the overall excellent prognosis for patients with PMC, the treatment of patients with T1-tumours of the new WHO-classification (including the "old" PMC) should be no different from the treatment of patients with conventional papillary thyroid carcinoma, i.e. complete surgery (TE and central lymph node dissection) followed by RIA of residual thyroid tissue. The authors argue that it is not appropriate to consider the tumour size as the single most important key factor for therapy and prognosis. Even small tumours may have poor prognostic factors, such as lymph node metastasis, multifocality or molecular characteristics (expression of oncogenes).

Contraindications↗

PET imaging with yttrium-86: comparison of phantom measurements acquired with different PET scanners before and after applying background subtraction.

Quantitative imaging with the positron emitter (86)Y is the method of choice to determine the uptake and dosimetry of (90)Y-labelled radiopharmaceuticals. To examine the quantitative accuracy of positron emission tomography findings with (86)Y, this non-pure positron emitter was evaluated in a cylindrical phantom with rods of Teflon, water and air and measured with three different scanners: ECAT EXACT (2D/3D), ECAT HR+ (2D/3D) and PC4096+ (2D). After standard reconstruction, (86)Y radioactivity measured with the ECAT EXACT and related to the true radioactivity varied between 0.84 and 0.99 in 2D and between 0.93 and 1.20 in 3D from the first to the last acquisition (eight half-life times later). The water and Teflon rods exhibited considerable amounts of reconstructed radioactivity-21% in 2D and 67% in 3D for water and 65% and 147%, respectively, for Teflon-compared with the actual (86)Y radioactivity of the phantom. For the ECAT HR+ similar results were obtained in 3D, but there were even greater overestimations in 2D. Measurements with the PC4096+ showed rather small errors, with 10% for water and 20% for Teflon. To correct for the background of gamma-coincidences, sinograms were analysed and an experimental percentage of the background was subtracted from the sinograms. In order to minimise the errors in reconstructed radioactivity, the subtraction value had to be different for the individual scanners and modes. Our results demonstrate that (90)Y/(86)Y-based dosimetry for bone and red marrow must be regarded with caution if it is derived from regions of interest over the bone, the density of which is similar to that of Teflon. To obtain more reliable estimates, an appropriate background correction must be applied and tailored individually with respect to the scanner and acquisition mode.

Algorithms↗

[Positron emission tomography for preoperative lymph node diagnosis in esophageal carcinoma].

BACKGROUND: Exact preoperative staging is a prerequisite for the indication and the choice of appropriate operative technique for patients with esophageal carcinoma. The objective of this prospective study was to assess whether positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) increases the accuracy of preoperative lymph node staging with standard computed tomography (CT) and thus leads to a different surgical approach. PATIENTS AND METHODS: Fifty-eight patients with carcinoma of the esophagus (46 men and 12 women) with a median age of 61 years underwent FDG-PET imaging of the neck, chest, and abdomen as well as CT of the chest and abdomen. Sensitivity, specificity, and accuracy were calculated for both imaging techniques to evaluate the detection of histologically verified lymph node metastases. RESULTS: The FDG-PET showed higher specificity, whereas CT proved to be more accurate for detecting lymph node metastases not only of the abdomen (73% vs 59%) but also of the thorax (73% vs 63%). Resections were transhiatal in 23 patients and transthoracal in 16. As a supplement to conventional CT diagnostic procedure, FDG-PET was not decisive for the surgical approach. CONCLUSIONS: Altogether, pretherapeutical PET imaging did not increase the accuracy of lymph node staging for our patients with esophageal carcinoma, which had already been defined through CT. Therefore, no new consequences resulted for the surgical procedure. Due to the high costs involved with PET investigation, lymph node staging with it is momentarily indicated mainly for clinical studies and when CT does not offer unequivocal results. Increased sensitivity of the already advantageous whole-body FDG-PET imaging by means of tumor-affinitive radiopharmaceuticals and optimized apparatus resolution could lead to new indications for this staging procedure.

Adenocarcinoma↗

[Anti-TNF antibodies in the treatment of inflammatory intestinal stenoses in Crohn's disease].

Stenoses are a frequent complication in patients with Crohn's disease and represent a major diagnostic and therapeutic challenge. The proper assessment of the nature of a stenosis as inflammatory or fibrotic is critical for appropriate treatment, since symptomatic fibrotic stenoses require surgical resection. Standard diagnostic procedures to assess the nature of a stenosis include endoscopy, conventional contrast radiography and magnetic resonance tomography. Recent data suggest, that the positron-emission-tomography possesses a high sensitivity and specificity to confirm inflammatory activity in the bowel. The recombinant monoclonal anti-TNF-antibody Infliximab (Remicade) has been approved for the treatment of steroid refractory and steroid dependent Crohn's disease in Germany since 9/2000 and the efficacy of Infliximab is well documented. However, few data exist about the treatment of inflammatory stenoses with Infliximab. We performed a retrospective analysis of our experience with Infliximab in patients with Crohn's disease with special reference to patients with inflammatory stenoses. Among a total of 21 patients treated with Infliximab 11 patients had an inflammatory stenosis. 9 of these patients responded well to Inflimab and became completely asymptomatic for a considerable period of time. Infliximab was tolerated well except for one patient who developed an intrabdominal abscess. The notable clinical response of patients with inflammatory stenoses to Infliximab suggests that treatment with Infliximab might be helpful to postpone or avoid surgical intervention. This finding should be further investigated in a prospective randomized study.

Adult↗

Dominance for vestibular cortical function in the non-dominant hemisphere.

The aim of this (15)O-labelled H(2)O bolus positron emission tomography (PET) study was to analyse the hemispheric dominance of the vestibular cortical system. Therefore, the differential effects of caloric vestibular stimulation (right or left ear irrigation with warm water at 44 degrees C) on cortical and subcortical activation were studied in 12 right-handed and 12 left-handed healthy volunteers. Caloric irrigation induces a direction-specific sensation of rotation and nystagmus. Significant regional cerebral blood flow increases were found in a network within both hemispheres, including the superior frontal gyrus/sulcus, the precentral gyrus and the inferior parietal lobule with the supramarginal gyrus. These areas correspond best to the cortical ocular motor centres, namely the prefrontal cortex, the frontal eye field and the parietal eye field, known to be involved in the processing of caloric nystagmus. Furthermore, distinct temporo-parietal activations could be separated in the posterior part of the insula with the adjacent superior temporal gyrus, the inferior parietal lobule and precuneus. These areas fit best to the human homologues of multisensory vestibular cortex areas identified in the monkey and correspond to the parieto-insular vestibular cortex (PIVC), the visual temporal sylvian area (VTS) and areas 7 and 6. Further cortical activations were seen in the anterior insula, the inferior frontal gyrus and anterior cingulum. The subcortical activation pattern in the putamen, thalamus and midbrain is consistent with the organization of efferent ocular motor pathways. Cortical and subcortical activation of the described areas was bilateral during monaural stimulation, but predominant in the hemisphere ipsilateral to the stimulated ear and exhibited a significant right hemispheric dominance for vestibular and ocular motor structures in right-handed volunteers. Similarly, a significant left hemispheric dominance was found in the 12 left-handed volunteers. Thus, this PET study showed for the first time that cortical and subcortical activation by vestibular caloric stimulation depends (i) on the handedness of the subjects and (ii) on the side of the stimulated ear. Maximum activation was therefore found when the non-dominant hemisphere was ipsilateral to the stimulated ear, i.e. in the right hemisphere of right-handed subjects during caloric irrigation of the right ear and in the left hemisphere of left-handed subjects during caloric irrigation of the left ear. The localization of handedness and vestibular dominance in opposite hemispheres might conceivably indicate that the vestibular system and its hemispheric dominance, which matures earlier during ontogenesis, determine right- or left-handedness.

Adult↗