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Biomedical subjects

P Bartenstein

Publications and source records attributed to P Bartenstein.

At least 19 recordsLinked to original sources

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↗

[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↗

Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome.

OBJECTIVES: To evaluate cerebral glucose metabolism, assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with chronic fatigue syndrome (CFS), using an observer independent analytical approach; and to characterise any observed alterations by correlating them with neuropsychological deficits. METHODS: 26 patients (13 female, 13 male) were examined. They all fulfilled the CDC diagnostic criteria for CFS. Their ages ranged from 26 to 61 years (mean (SD) age, 43 (9.3) years). They underwent extensive psychometric testing including the hospital anxiety and depression scale (HADS) and the short form 36 item health questionnaire (SF-36). Brain FDG-PET was done in all the subjects. After stereotactic normalisation, single subject comparisons with an age and sex matched normal database (n = 18) and a group comparison between the patients and normal controls were undertaken, along with additional correlation analyses between brain metabolism and psychometric test scores. RESULTS: 12 of the 26 patients showed no significant decrease in FDG uptake compared with the controls. Of the remaining 14, 12 showed hypometabolism bilaterally in the cingulate gyrus and the adjacent mesial cortical areas. Five of these 12 patients also had decreased metabolism in the orbitofrontal cortex. The two remaining patients had hypometabolism in the cuneus/praecuneus. Correlation analyses showed significant correlations between some test scores (anxiety, depression, health related quality of life) but not fatigue and regional reductions in glucose metabolism. CONCLUSIONS: Although abnormalities in FDG-PET were only detectable in approximately half the CFS patients examined, and no specific pattern for CFS could be identified, PET may provide valuable information in helping to separate CFS patients into subpopulations with and without apparent alterations in the central nervous system.

Adult↗

[18F-Deoxyglucose PET for the staging of oesophageal cancer: influence of histopathological subtype and tumour grading].

AIM: Evaluation of the influence of histopathologic sub-types and grading of primaries of oesophageal cancer, relative to their size and location, on the uptake of (18)F-deoxyglucose (FDG) as measured by positron emission tomography (PET). METHODS: 50 consecutive patients were evaluated. There were four drop-outs due to previous surgical and/or chemotherapeutical treatments and thus in 46 patients (28 squamous cell carcinomas and 18 adenocarcinomas) a pretherapeutic PET evaluation of the primary including a standard uptake value (SUV) was obtained. In 42 cases data on tumour grading were available also. RESULTS: Squamous cell carcinomas (SCC) were in 7/13/8 cases located in the proximal, medial and distal part of the oesophagus, respectively the grading was Gx in 3, G 2 in 12, G2-3 in 7, and G3 in 6 cases. The SUV(max) showed a mean of 6.5+/-2.8 (range 1.7-13.5). Adenocarcinomas (ACA) were located in the medial oesophagus in two cases and otherwise in its distal parts. Grading was Gx in one, G2 in 4, G2-3 in 3, G3 in 3, G3-4 in 3, and G4 in one case. The mean SUV(max) was 5.2+/-3.2 (range 1-13.6) and this was not significantly different from the SCC. Concerning the tumour grading there was a slight, statistically not relevant trend towards higher SUV(max) in more dedifferentiated cancer. DISCUSSION: SCC and ACA of the oesophagus show no relevant differences in the FDG-uptake. While there was a significant variability of tumour uptake in the overall study group, a correlation of SUV and tumour grading was not found.

Adenocarcinoma↗

[Positron emission tomography for the preoperative staging of esophageal carcinoma].

BACKGROUND AND OBJECTIVE: Exact preoperative staging is a prerequisite for the indication as well as the choice of the appropriate operative technique for patients with esophageal carcinoma. In this prospective study we assessed whether positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) increases the accuracy of staging compared to standard computer tomography (CT) and leads to a different therapeutic approach. PATIENTS AND METHODS: 30 patients (25 men, 5 women, median age 63 years) with histologically identified carcinoma of the esophagus (n =29) and the cardia (n = 1), respectively, were studied. All patients 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 FDG-PET and CT to evaluate the detection of histologically identified lymph node metastases and distant metastatic disease. RESULTS: FDG-PET showed higher specificity whereas the accuracy of the CT proved to be higher not only for the detection of abdominal lymph node metastases (67 % vs. 46 %), but also for lymph node metastases of the thorax (71 % vs. 50 %). Furthermore, the accuracy of the CT for the detection of blood-bone and lymphatic distant metastases was also higher than that of FDG-PET (72 % vs. 68 %). FDG-PET was more specific (100 % vs. 71 %) albeit less sensitive than CT-imaging (27 % vs. 73 %). CONCLUSION: In our study, FDG-PET did not increase the accuracy of standard staging (CT) in patients with carcinoma of the esophagus. Therefore, no new consequences resulted for the operative indication as well as therapeutic procedure. Due to the high costs involved with PET investigation, this form of staging is momentarily indicated mainly for use in clinical studies, and in cases where CT does not offer unequivocal results. Increase in sensitivity of the already advantageous whole-body FDG-PET imaging by means of tumor-affinitive radiopharmaceuticals as well as optimized apparatus resolution could lead to new indications for this staging procedure.

Carcinoma↗

Noninvasive assessment of Crohn's disease activity: a comparison of 18F-fluorodeoxyglucose positron emission tomography, hydromagnetic resonance imaging, and granulocyte scintigraphy with labeled antibodies.

OBJECTIVES: Detection of disease activity in Crohn's disease (CD) is of crucial importance for diagnosis and management of the disease. Noninvasive methods for monitoring are desirable and comprise hydromagnetic resonance imaging (hydro-MRI) and leukocyte scintigraphy. In addition, a recent case report indicated the potential of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to assess CD activity. However, comparative prospective studies are lacking. METHODS: Between February, 1999 and August, 2000, 59 patients with CD were enrolled in a prospective study to assess disease activity by FDG-PET, hydro-MRI, and immunoscintigraphy with anti-nonspecific cross-reacting antigen 95 antigranulocyte antibodies. In 28 of these patients, colonoscopy could be performed. Twelve patients with irritable bowel syndrome and 20 tumor patients without gut inflammation served as controls. Results were compared by statistical analysis. RESULTS: FDG-PET detected 127 pathological findings (average maximum standardized uptake value = 4.4 +/- 1.1) in the terminal/neoterminal ileum (37), small bowel (24), and colon (66) of 54 patients with CD, whereas no pathological findings were seen in five patients with CD, the control patients with irritable bowel syndrome, and the tumor patients without gut inflammation. In contrast, examination with hydro-MRI or granulocyte antibodies detected less pathological findings in CD patients. Forty-five of the detected foci were accessible to endoscopic verification. The correlation of the foci with endoscopic findings showed a high specificity (>89%) of all three methods to detect inflamed areas in the terminal ileum and colon of patients with CD, although analyses by hydro-MRI and granulocyte antibody scan had strikingly lower sensitivities (40.9% and 66.7%) than FDG-PET analysis (85.4%). CONCLUSIONS: FDG-PET appears to be a reliable noninvasive tool for simultaneous detection of inflamed areas in the small and large bowel of patients with CD. FDG-PET can be used to detect disease activity in the terminal ileum and colon of CD patients with high sensitivity and specificity.

Adult↗

A H(2)(15)O positron emission tomography study on mental imagery of movement sequences--the effect of modulating sequence length and direction.

Motor imagery is a state of mental rehearsal of single movements or movement patterns and has been shown to recruit motor networks overlapping with those activated during movement execution. We wished to examine whether the brain areas subserving control of sequential processes could be delineated by pure mental imagery, their activation levels reflecting the processing demands of a sequential task. We studied six right-handed volunteers (39.0 +/- 14 years) with H(2)(15)O positron emission tomography (PET) while they continuously mentally pursued with their right hand one of five sequences differing in complexity (i.e., increases in sequence length, single-finger repetitions, and reversals). Conditions were repeated twice, alternating with two rest scans. Each imagined single motor element was paced at a frequency of 1 Hz. Significant activation increases (P < 0.05, corrected) associated with imagination of right finger movement sequences (conditions I to V combined)--compared to the rest condition--were observed in left sensorimotor cortex (M1/S1) and the adjacent inferior parietal cortex. Further activation increases (P < 0.001, uncorrected) occurred in bilateral dorsal premotor (PMd) cortex, left caudal supplementary motor area, bilateral ventral premotor cortex, right M1, left superior parietal cortex, left putamen, and right cerebellum. Activation decreases occurred in bilateral prefrontal and right temporo-occipital cortex. Activation increases that correlated with sequence complexity were observed only in specific areas of the activated network, notably in left PMd, right superior parietal cortex, and right cerebellar vermis (P < 0.05, corrected). In conclusion, our study, by varying the sequence structure of imagined finger movements, identified task-related activity changes in parietopremotor-cerebellar structures, reflecting their role in mediating sequence control.

Adult↗

PET in patients with clear-cut multiple chemical sensitivity (MCS).

AIM: Multiple chemical sensitivity (MCS) is a controversially discussed symptom complex. Patients afflicted by MCS react to very low and generally non-toxic concentrations of environmental chemicals. It has been suggested that MCS leads to neurotoxic damage or neuroimmunological alteration in the brain detectable by position emission tomography (PET) and single photon emission computer tomography (SPECT). These methods are often applied to MCS patients for diagnosis, although they never proved appropriate. METHOD: We scanned 12 MCS patients with PET, hypothesizing that it would reveal abnormal findings. RESULTS: Mild glucose hypometabolism was present in one patient. In comparison with normal controls, the patient group showed no significant functional brain changes. CONCLUSION: This first systematic PET study in MCS patients revealed no hint of neurotoxic or neuroimmunological brain changes of functional significance.

Adult↗

Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex.

BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.

Adult↗

Activation of frontal premotor areas during suprathreshold transcranial magnetic stimulation of the left primary sensorimotor cortex: a glucose metabolic PET study.

We employed cerebral (18)Fluoro-deoxyglucose positron emission tomography ([(18)F]FDG-PET) to visualize neuronal activation of the frontal motor and premotor cortex during suprathreshold repetitive transcranial magnetic stimulation (rTMS) applied to the left primary sensorimotor hand area (SM1(HAND)). Twelve right-handed normal subjects underwent two [(18)F]FDG-PET measurements at baseline without rTMS and during suprathreshold 2 Hz rTMS of the left SM1(HAND). In the rTMS condition, 1,800 magnetic stimuli at an intensity of 140% of motor-resting threshold were delivered immediately after intravenous injection of [(18)F]FDG. Relative differences in the normalized regional cerebral metabolic rate for glucose (rCMRglc) between the rTMS condition and baseline were determined using a voxel-by-voxel Student's t-test and a volume-of-interest analysis. Data analysis was a priori restricted to primary motor and premotor areas in the frontal cortex, namely the SM1, the supplementary motor area (SMA), the lateral premotor cortex (PMC), and the caudal anterior cingulate cortex (ACC) of either hemisphere. In addition to a relative increase in normalized rCMRglc in the stimulated SM1(HAND), suprathreshold rTMS was associated with well-localized increases in normalized rCMRglc in the caudal SMA and ACC on the medial wall of the frontal cortex and in the right precentral gyrus in the lateral PMC rostrally to the SM1. These data demonstrate that a selective activation of the SM1(HAND) is paralleled by an activation of a distinct set of remote premotor areas, suggesting a functional interaction between the primary motor and premotor cortex in humans.

Adult↗

Cortical correlates of gesture processing: clues to the cerebral mechanisms underlying apraxia during the imitation of meaningless gestures.

The clinical test of imitation of meaningless gestures is highly sensitive in revealing limb apraxia after dominant left brain damage. To relate lesion locations in apraxic patients to functional brain activation and to reveal the neuronal network subserving gesture representation, repeated H2(15O)-PET measurements were made in seven healthy subjects during a gesture discrimination task. Observing paired images of either meaningless hand or meaningless finger gestures, subjects had to indicate whether they were identical or different. As a control condition subjects simply had to indicate whether two portrayed persons were identical or not. Brain activity during the discrimination of hand gestures was strongly lateralized to the left hemisphere, a prominent peak activation being localized within the inferior parietal cortex (BA40). The discrimination of finger gestures induced a more symmetrical activation and rCBF peaks in the right intraparietal sulcus and in medial visual association areas (BA18/19). Two additional foci of prominent rCBF increase were found. One focus was located at the left lateral occipitotemporal junction (BA 19/37) and was related to both tasks; the other in the pre-SMA was particularly related to hand gestures. The pattern of task-dependent activation corresponds closely to the predictions made from the clinical findings, and underlines the left brain dominance for meaningless hand gestures and the critical involvement of the parietal cortex. The lateral visual association areas appear to support first stages of gesture representation, and the parietal cortex is part of the dorsal action stream. Finger gestures may require in addition precise visual analysis and spatial attention enabled by occipital and right intraparietal activity. Pre-SMA activity during the perception of hand gestures may reflect engagement of a network that is intimately related to gesture execution.

Adult↗

[18F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors.

5-(2'-[18F]Fluoroethyl)flumazenil ([18F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [11C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [L8F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A third subject was studied both with [18F]FEF and with [11C]flumazenil. Brain radioactivity was measured for 60-90 min p.i. and analysed with a region of interest-oriented approach and on a voxelwise basis with spectral analysis. Plasma radioactivity was determined from arterial blood samples and metabolites were determined by high-performance liquid chromatography. In human brain, maximum radioactivity accumulation was observed 4 +/- 2 min p.i., with a fast clearance kinetics resulting in 50% and 20% of maximal activities at about 10 and 30 min, respectively. [18F]FEF uptake followed the known central benzodiazepine receptor distribution in the human brain (occipital cortex >temporal cortex >cerebellum >thalamus >pons). Pretreatment with unlabelled flumazenil resulted in reduced tracer uptake in all brain areas except for receptor-free reference regions like the pons. Parametric images of distribution volume and binding potential generated on a voxelwise basis revealed two- to three-fold lower in vivo receptor binding of [18F]FEF compared with [11C]flumazenil, while relative uptake of [18F]FEF was higher in the cerebellum, most likely owing to its relatively higher affinity for benzodiazepine receptors containing the alpha6 subunit. Metabolism of [18F]FEF was very rapid. Polar metabolites represented about 50%-60% of total plasma radioactivity at 5 min and 80%-90% at 20 min p.i. Although [11C]flumazenil has some advantages over [18F]FEF (higher affinity, slower metabolism, slower kinetics), our results indicate that [18F]FEF is a suitable PET ligand for quantitative assessment of central benzodiazepine receptors, which can be used independently of an on-site cyclotron.

Brain↗

Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies.

The aim of this study was to identify the functional cerebral network involved in the central processing of itch and to detect analogies and differences to previously identified cerebral activation patterns triggered by painful noxious stimuli. Repeated positron emission tomography regional cerebral blood flow (rCBF) measurements using O15-labeled water were performed in six healthy right-handed male subjects (mean age 32 +/- 2 years). Each subject underwent 12 sequential rCBF measurements. In all subjects a standardized skin prick test was performed on the right forearm 2 min before each rCBF measurement. For activation, histamine was applied in nine tests in logarithmically increasing concentrations from 0.03 to 8%. Three tests were performed with isotonic saline solution serving as a control condition. Itch intensity and unpleasantness were registered with a visual analogue scale during each test. Subtraction analysis between activation and control conditions as well as correlation analysis with covariates were performed. Itch induced a significant activation in the predominantly contralateral somatosensory cortex and in the ipsilateral and contralateral motor areas (supplementary motor area (SMA), premotor cortex, primary motor cortex). Additional significant activations were found in the prefrontal cortex and the cingulate gyrus, but not in subcortical structures nor in the secondary somatosensory cortex. In correlation analyses, several cortical areas showed a graded increase in rCBF with the logarithm of the histamine concentration (bilateral sensorimotor areas and cingulate cortex; contralateral insula, superior temporal cortex and prefrontal cortex) and with itch unpleasantness (contralateral sensorimotor cortex, prefrontal cortex and posterior insula; ipsilateral SMA). Induction of itch results in the activation of a distributed cerebral network. Itch and pain seem to share common pathways (a medial and a lateral processing pathway and a strong projection to the motor system). In contrast to pain activation studies, no subcortical (i.e. thalamic) activations were detected and correlation analyses suggest differences in subjective processing of the two sensations.

Adult↗

Brain correlates of fast and slow handwriting in humans: a PET-performance correlation analysis.

The present study examined the cerebral control of velocity during handwriting. We employed H215O positron emission tomography (PET) to measure the regional cerebral blood flow (rCBF) in 10 healthy subjects. Participants were required to write the German verb 'bellen' ('to bark') either at their normal speed (i.e. fast open-loop handwriting) or to write at approximately half of their normal speed without visual feedback. The second task required a continuous modification of the motor output according to the kinaesthetic feedback from the hand (i.e. slow closed-loop handwriting). Pencil movements were recorded during PET scanning and analysed off-line using a stroke-based analysing program. The mean number of inversions in velocity (NIV) per stroke was used to quantify the mode of motor control during each PET scan. A NIV of 1 indicates fast open-loop processing, whereas an increase in NIV reflects a shift towards slow closed-loop processing of handwriting. Foci in the left primary sensorimotor cortex, the right lateral premotor cortex, the left anterior parietal cortex, the left anterior putamen, the left rostral supplementary motor area and the right precuneus showed a graded increase in functional activation with the mean NIV per stroke, suggesting that this set of brain regions is particularly involved in the processing of slow closed-loop writing movements. No area showed a negative relationship between rCBF and the mean NIV per stroke, suggesting that fast open-loop handwriting is achieved by an optimized cooperation of the manual sensorimotor network rather than by a selective activation of a distinct network component.

Adult↗