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ABSTRACT: Alterations of the central serotonergic system are considered to be involved in the pathophysiology of borderline personality disorder (BPD). The loudness dependence of the N1/P2 component of auditory evoked potentials (LD) has been shown to indirectly reflect central serotonergic activity. The aim of this study was to investigate LD in patients with BPD compared to healthy controls, and to evaluate the association between LD and psychopathology such as anxiety, anger or impulsiveness. Female patients with BPD were included and compared to age and sex matched healthy subjects. Self-rating instruments, such as State-Trait Anxiety Inventory (STAI), State-Trait Anger Expression Inventory (STAXI), and the Barratt Impulsiveness Scale (BIS) were used to assess clinical scores of anxiety, anger, and impulsiveness. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analysed using dipole source analysis. The mean LD was significantly higher in patients with BPD compared to controls. In the entire sample there were significant positive correlations of LD with state anxiety scores and STAXI subscores. The data contribute to the knowledge of neurophysiological alterations in patients with BPD, supporting the hypothesis of serotonergic dysregulation in the pathophysiology of the disorder. The significant clinical correlations suggest monoaminergic modulations of psychopathology on the symptom level.
Psychiatry Research 04/2012; · 2.52 Impact Factor
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ABSTRACT: The P300 is a cortically generated event related potential (ERP) widely used in neurophysiological research since it is related to cognitive functions and central information processing. Intracerebral recordings and functional neuroimaging studies have demonstrated that this potential is generated by various brain regions including frontal, temporal and parietal cortices. Regarding the neurochemical background, clinical and genetic investigations suggest that dopaminergic neurons could be involved in the generation of the P300. However, there is no direct evidence in vivo that P300 amplitudes and latencies are related to dopaminergic parameters. The aim of this study was to further elucidate dopaminergic aspects of the P300 ERP by combining neurophysiological and nuclear medicine assessments in vivo. Patients with a major depressive episode underwent both P300 recordings and dynamic [¹²³I] IBZM SPECT for the evaluation of striatal dopamine D₂/D₃-receptor availability. There were statistically significant positive correlations of the striatal dopamine D₂/D₃-receptor status with P300 amplitudes and significant negative correlations with P300 latencies. Using this combined approach, the study presents direct evidence in vivo that the central dopaminergic system might play an important role in the generation of the P300 and that central dopaminergic activity could be involved in the modulation of P300 parameters. This association might be of relevance for the interpretation of P300 studies in psychiatric disorders.
Psychiatry Research 11/2011; 194(3):212-8. · 2.52 Impact Factor
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ABSTRACT: In routine clinical practice striatal dopamine D(2) receptor binding is generally assessed using data reconstructed by filtered backprojection (FBP). The aim of this study was to investigate the use of an iterative reconstruction algorithm (ordered subset expectation maximization, OSEM) and to assess whether it may provide comparable or even better results than those obtained by standard FBP.
In 56 patients with parkinsonian syndromes, single photon emission computed tomography (SPECT) scans were acquired 2 h after i.v. application of 185 MBq [(123)I]iodobenzamide (IBZM) using a triple-head gamma camera (Siemens MS 3). The scans were reconstructed both by FBP and OSEM (3 iterations, 8 subsets) and filtered using a Butterworth filter. After attenuation correction the studies were automatically fitted to a mean template with a corresponding 3-D volume of interest (VOI) map covering striatum (S), caudate (C), putamen (P) and several reference VOIs using BRASS software.
Visual assessment of the fitted studies suggests a better separation between C and P in studies reconstructed by OSEM than FBP. Unspecific background activity appears more homogeneous after iterative reconstruction. The correlation shows a good accordance of dopamine receptor binding using FBP and OSEM (intra-class correlation coefficients S: 0.87; C: 0.88; P: 0.84). Receiver-operating characteristic (ROC) analyses show comparable diagnostic power of OSEM and FBP in the differentiation between idiopathic parkinsonian syndrome (IPS) and non-IPS.
Iterative reconstruction of IBZM SPECT studies for assessment of the D(2) receptors is feasible in routine clinical practice. Close correlations between FBP and OSEM data suggest that iteratively reconstructed IBZM studies allow reliable quantification of dopamine receptor binding even though a gain in diagnostic power could not be demonstrated.
European Journal of Nuclear Medicine 02/2011; 38(6):1095-103. · 4.53 Impact Factor
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ABSTRACT: The in vivo assessment of brain serotonergic function might be of clinical relevance in neuropsychiatry. The loudness dependence of auditory evoked potentials (LD) has been proposed as an indirect indicator of cortical serotonergic activity, whereas single photon emission computed tomography (SPECT) and [123I]ADAM allow the selective assessment of brain serotonin transporters (SERT). The aim of this study was to investigate LD and SERT availability as independent variables of the brain serotonergic system in healthy volunteers. Fifteen (six male, nine female) subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analyzed using dipole source analysis. SPECT was performed four hours after injection of 137 +/- 11.4 MBq [123I]ADAM. As a measure of SERT availability specific ADAM brainstem binding was used. LD correlated significantly with SERT availability (Pearson's correlations: rho = -0.57, p < 0.05). The correlations remained significant after controlling for the effects of age or gender (partial correlations: rho = -0.60, p < 0.05) but were pronounced in the female group (rho = -0.83, p < 0.01). Associations between LD and SERT availability contribute to the understanding of the central serotonergic system and further validate the use of neurophysiological approaches as indirect measures of neurochemical brain activity.
European Archives of Psychiatry and Clinical Neuroscience 02/2008; 258(1):40-7. · 3.49 Impact Factor
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ABSTRACT: Treatment and prognosis of gliomas depend on their histological tumour grade. The aim of the study was to evaluate the potential of [(18)F]fluoroethyltyrosine (FET) PET for non-invasive tumour grading in untreated patients.
Dynamic FET PET studies were performed in 54 patients who, based on MRI, were estimated to have low grade (LG; n = 20), intermediate (WHO II-III; n = 4) or high grade (HG; n = 30) tumours. For standard evaluation, tumour SUV(max) and the ratio to background (SUV(max)/BG) were calculated (sum image: 20-40 min). For dynamic evaluation, mean SUV values within a 90% isocontour ROI (SUV90) and the SUV90/BG ratios were determined for each time frame to evaluate the course of FET uptake. Results were correlated with histopathological findings from PET-guided stereotactic biopsies.
Histology revealed gliomas in all patients. Using the standard method a statistically significant difference (p = 0.001) was found between LG (n = 20; SUV(max)/BG: 2.16 +/- 0.98) and HG (n = 34; SUV(max)/BG: 3.29 +/- 1.06) gliomas (opt. threshold 2.58: SN71%/SP85%/area under ROC curve [AUC]:0.798), however, with a marked overlap between WHO II to IV tumours. Time activity curves showed slight increase in LG, whereas HG tumours presented with an early peak (10-20 min) followed by a decrease. Dynamic evaluation successfully separated LG from HG gliomas with higher diagnostic accuracy (SN94%/SP100%/AUC:0.967).
Based on the ratio-based method, a statistically significant difference was found between LG and HG gliomas. Due to the interindividual variability, however, no reliable individual grading was possible. In contrast, dynamic evaluation allowed LG and HG gliomas to be differentiated with high diagnostic power and, thus, should supplement the conventional method.
European journal of nuclear medicine and molecular imaging 01/2008; 34(12):1933-42. · 4.99 Impact Factor
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Oliver Pogarell, Walter Koch,
Gabriele Pöpperl,
Klaus Tatsch,
Franziska Jakob,
Christoph Mulert,
Nicola Grossheinrich,
Rainer Rupprecht,
Hans-Jürgen Möller,
Ulrich Hegerl,
Frank Padberg
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ABSTRACT: Prefrontal repetitive transcranial magnetic stimulation (rTMS) has been shown to increase striatal dopaminergic activity. Here we investigated dopaminergic neurotransmission using single photon emission computed tomography (SPECT) and [(123)I]IBZM to indirectly assess the change in endogenous striatal dopamine concentration upon rTMS as compared with d-amphetamine challenge. SPECT imaging was performed twice each in five patients during rTMS, and in two patients who received 0.3 mg/kg D-amphetamine. Administration of rTMS led to a mean relative decrease in striatal IBZM binding by 9.6+/-6.2%, and d-amphetamine challenge (n=4) induced a mean relative reduction by 8+/-2.95% (difference not statistically significant). Acute rTMS challenge showed similar striatal dopaminergic effects to those associated with the administration of d-amphetamine, a substance known to increase synaptic dopamine.
Psychiatry Research 01/2008; 156(3):251-5. · 2.52 Impact Factor
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ABSTRACT: Head motion during acquisition is a frequently observed phenomenon while imaging the brain with SPECT. The aim of this study was to obtain detailed insight into the effects of head motion on the specific striatal binding of I-FP-CIT based on Monte Carlo simulations.
Based on the Monte Carlo code and the digital Zubal phantom, different movement profiles (angular movement in the transaxial and sagittal plane ranging from -10 to +10 degrees) were systematically simulated for normal striatal binding and neurodegeneration. A triple-headed SPECT camera equipped with low-energy, high-resolution, parallel-hole collimators was modelled for this purpose. The projection data were reconstructed iteratively and the images were then evaluated using fully automated quantification software based on morphology guided volumes of interest. In addition, data were evaluated with a method taking into account partial volume effects.
Simulated movement resulted in blurring and streaking of the striatal structures with a concomitant change in measured specific striatal binding in most simulated profiles ranging from -44% to +2% (for the morphology guided volume of interest analyses) and -23% to +28% (for the method intended to overcome partial volume effects). In contrast to angular movement in the sagittal plane, rotation in the transaxial plane caused left/right asymmetry up to 41%. In the simulation of neurodegeneration, almost all movement profiles lead to an increase of putamen-to-caudate ratios.
Motion during the acquisition of a SPECT scan can have an important impact on measured dopamine transporter binding with its extent varying in dependency on the method of analysis used. While this is of prime importance in a research setting, it can also have implications in clinical routine imaging.
Nuclear Medicine Communications 09/2007; 28(8):603-14. · 1.40 Impact Factor
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ABSTRACT: We hypothesized that combining pre- and postsynaptic quantitative information about the dopaminergic system would provide a higher diagnostic accuracy in the differential diagnosis of parkinsonism than specific striatal D(2) receptor binding alone. Therefore, the aim of the study was to introduce new semi-quantitative parameters and evaluate their ability to discriminate between Parkinson's disease (IPS) and non-idiopathic parkinsonian syndromes (non-IPS).
In 100 patients (69 IPS, 31 non-IPS), postsynaptic [(123)I]IBZM and presynaptic [(123)I]FP-CIT SPECT scans were evaluated by observer-independent techniques. The diagnostic performances of striatal dopamine transporter (DAT) and D(2) receptor binding, their respective asymmetries, and a combination of pre- and postsynaptic asymmetry were evaluated with ROC analyses. A logistic regression model was generated combining factors to calculate the probability for each patient of belonging to either diagnostic group.
D(2) receptor binding provided a sensitivity of 87.1% and a specificity of 72.5% with an area under the curve (AUC) of 0.866. The AUCs of other single parameters were lower than that of D(2) binding. A gain of diagnostic power (p = 0.026) was reached with a model combining pre- and postsynaptic asymmetries and D(2) binding (sensitivity 90.3%, specificity 73.9%, AUC 0.893).
The combination of quantitative parameters of presynaptic DAT and postsynaptic D(2) receptor binding demonstrates superior diagnostic power in the differentiation of patients with IPS and non-IPS than the established approach based on D(2) binding alone. Striatal D(2) receptor binding and the combination of DAT and IBZM binding asymmetries are the factors contributing most in separating these diagnostic groups.
European journal of nuclear medicine and molecular imaging 09/2007; 34(8):1265-73. · 4.99 Impact Factor
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Walter Koch,
Nadine Schaaff,
Gabriele Pöpperl,
Christoph Mulert,
Georg Juckel,
Markus Reicherzer,
Christoff Ehmer-von Geiso,
Hans-Jürgen Möller,
Ulrich Hegerl,
Klaus Tatsch,
Oliver Pogarell
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ABSTRACT: Serotonergic dysfunction is considered to be involved in the pathophysiology of borderline personality disorder (BPD). The aim of this study was to investigate serotonin transporter availability in patients with BPD as a marker of the central serotonergic system.
Eight unmedicated patients with BPD and 9 healthy control subjects received single photon emission computed tomography (SPECT) 4 hours after injection of 185 MBq [I-123] ADAM (2-([2-([dimethylamino]methyl)phenyl]thio)). As a measure of brain serotonin transporter (SERT) availability, ratios of specific-to-nonspecific [I-123] ADAM binding for the brainstem and hypothalamus were calculated with an occipital reference. Levels of impulsiveness and depressive symptoms were assessed with the Barratt Impulsiveness Scale and the Beck Depression Inventory.
Mean specific-to-nonspecific ratios showed a 43% higher brainstem and a 12% higher hypothalamus ADAM binding in patients, compared with control subjects. We found significant correlations of ADAM binding with both age and impulsiveness but not depression. Associations of BIS scores with ADAM binding remained significant after controlling for age and depression (r = 0.69, p < 0.01).
The study provides evidence of a serotonergic dysfunction in patients with BPD and suggests a serotonergic component in the pathophysiology of the disorder. SERT binding reflected the level of impulsiveness as a common feature in BPD.
Journal of psychiatry & neuroscience: JPN 08/2007; 32(4):234-40. · 5.34 Impact Factor
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ABSTRACT: The purpose was to determine the response and survival and to analyse the feasibility of single-session, whole-liver SIRT in patients with non-resectable, otherwise non-responding liver cancer. Thirty-nine patients qualified for SIRT. Eighteen patients suffered from colorectal-cancer metastases (CRC), breast-cancer metastases (MBC, 7), HCC (5) and other tumours (9). Response was assessed by tumour-markers and CT-imaging. At 2-4, 5-7 and 8-9 months follow-up in 3/17, 5/15 and 5/10 of CRC-patients CEA-levels were higher than before. In the MBC group 1-3 and 4-6 months after SIRT tumour-marker-levels were higher in 2/6 and 3/3 patients, respectively. In all HCC-patients AFP-levels dropped 1-3 months after SIRT. Using RECIST, in the CRC-group progressive liver disease (PD) was found in 4/17, 2/12, 2/10 and 2/5 patients at 2-4, 5-8, 9-10 and 12-14 months follow-up. Concerning MBC, after 3 months 7/7 patients presented with stable-disease (SD) or partial-response (PR). At 5-6 months, 1/5 patients showed PD. All HCC-patients showed SD/PR at 2-3 months with no PD at 5-8 months. In the mixed-group 5/6 patients presented with SD/PR at 3-4 months and with SD in 2/3 patients at 5-6 months. The median time-to-PD was 6.5, 8.5 and 8 months for the CRC-, MBC- and mixed-group, respectively. SIRT is a promising, liver-targeted approach for patients with otherwise treatment-refractory liver tumours.
European Radiology 06/2007; 17(5):1320-30. · 3.22 Impact Factor
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ABSTRACT: This study evaluates a new formulation of a (99m)Tc-labeled tropane derivate, (99m)Tc-NC100697, in a human volunteer study.
Eighty healthy subjects (39 females, 41 males) underwent MRI and SPECT (injected dose [mean +/- SD], 10.6 +/- 1.4 MBq/kg). Forty subjects were investigated 30, 90, 180, 240, 360, and 480 min after injection, and another 40 subjects were imaged 240 min after injection. Specific striatal binding was assessed using 3 different approaches: 3-dimensional volumes of interest (VOIs) drawn on the coregistered MRI scans, manually placed predefined 2-dimensional regions of interest (ROIs), and observer-independent fully automated 3-dimensional VOI analyses based on coregistration of scans with a mean template of controls. Specific striatal dopamine transporter (DAT) binding was estimated for cohorts of ages of 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 y. The relationship between age and DAT binding was analyzed with linear, "broken-stick," exponential, and logarithmic regression.
Serial SPECT scans revealed increasing values of specific DAT binding over time. Consideration of all important variables suggests an optimum imaging time at 4 h after injection. Average DAT binding for the total population was 1.1 +/- 0.2 (striatum), 1.3 +/- 0.2 (caudate), and 1.1 +/- 0.2 (putamen), with mean putamen-to-caudate ratios of 0.83 +/- 0.08 (manual 2-dimensional ROI method). A significant age dependency of striatal DAT binding, best described by a broken-stick (break-point age, 48 y) or logarithmic regression (both r = 0.76), with a lower decline observed in older than in younger subjects. Female subjects presented with slightly higher binding ratios than male subjects, more pronounced in pre- than in postmenopausal women. There was a high correlation between the 3 semiquantitative evaluations.
The current study has demonstrated the effective use of (99m)Tc-NC100697 for estimating presynaptic striatal DAT binding. The comparison of different semiquantification methods showed that in clinical routine work, this tracer can be reliably evaluated without individual MRI data. Age and a slight sex dependency (especially in premenopausal women) of (99m)Tc-NC100697 binding should be taken into consideration. The data generated in this phase 1 study provides a basis for an age- and sex-matched normal database.
Journal of Nuclear Medicine 02/2007; 48(1):27-34. · 6.38 Impact Factor
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ABSTRACT: In a previous study, binding of Tc-TRODAT-1 to the dopamine transporter (DAT) was found to be higher in patients with attention deficit hyperactivity disorder (ADHD) as compared to healthy controls.
To determine whether the degree of Tc-TRODAT-1 binding to the striatal DAT may have a predictive role on the response to methylphenidate (MPH) in patients with ADHD.
Twenty-two adult patients suffering from ADHD underwent a brain SPECT scan with Tc-TRODAT-1. After the scan patients received MPH, individually medicated up to 60 mg.day. Severity of illness was estimated using the Clinical Global Impression (CGI-S) Scale before treatment. Ten weeks after the beginning of MPH treatment the improvement in global symptoms was rated by the Clinical Global Improvement Scale (CGI-I).
Before treatment 17/22 patients with ADHD presented with higher striatal DAT binding as compared to age-matched healthy controls (+23.8%; P<0.01). After treatment with MPH a significant improvement of ADHD symptoms was demonstrated by the CGI-I in 16 of these 17 patients (CGI-S before: 4.8; CGI-I after MPH: 1.9; P<0.01). Five patients showed reduced DAT binding prior to therapy (-14.4%; P=0.04); these patients did not respond to MPH therapy (CGI-S before: 4.5; CGI-I after MPH: 4.2; P=0.40).
Our findings suggest that ADHD patients with primarily elevated binding of Tc-TRODAT-1 to the striatal DAT responded better to therapy with MPH as compared to those with normal or low DAT binding. Consequently, our results - even if obtained on a small collective indicate that measurement of DAT may be an important prognostic predictor for therapy response to MPH.
Nuclear Medicine Communications 10/2006; 27(9):733-7. · 1.40 Impact Factor
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Oliver Pogarell, Walter Koch,
Gabriele Pöpperl,
Klaus Tatsch,
Franziska Jakob,
Peter Zwanzger,
Christoph Mulert,
Rainer Rupprecht,
Hans-Jürgen Möller,
Ulrich Hegerl,
Frank Padberg
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ABSTRACT: Though there is considerable evidence that prefrontal repetitive transcranial magnetic stimulation (rTMS) exerts antidepressant effects, the neurobiological action of rTMS in patients with depression is poorly understood. Preclinical studies in animals and humans have demonstrated that prefrontal rTMS can induce dopamine release in mesostriatal and mesolimbic regions. We therefore investigated whether rTMS also modulates striatal dopaminergic neurotransmission in depressed patients using a dynamic [123I] iodobenzamide (IBZM) single photon emission computed tomography (SPECT) approach. Five patients with a major depressive episode (DSM-IV) underwent an acute 10 Hz rTMS challenge with 3000 stimuli over the left dorsolateral prefrontal cortex during an [123I] IBZM-SPECT bolus and constant infusion protocol. In four subjects the protocol was repeated after a three week rTMS standard treatment. Striatal IBZM binding to dopamine D2 receptors was assessed with a region-of-interest (ROI) technique. The change in striatal IBZM binding after the rTMS challenge was regarded as measure of change in endogenous striatal dopamine. Data of nine SPECT investigations showed a significant reduction by 9.6+/-6.2% in IBZM binding to striatal dopamine D2 receptors after rTMS challenge compared to baseline (p=0.01, Wilcoxon test). In this preliminary study, the reduction of IBZM binding observed after rTMS challenge is suggestive of a release in endogenous dopamine induced by prefrontal rTMS. In future, this approach can be used to differentiate specific and non-specific reward-related effects of rTMS on dopaminergic neurotransmission.
Journal of Psychiatric Research 07/2006; 40(4):307-14. · 4.66 Impact Factor
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ABSTRACT: SPECT examinations of neurotransmitter systems in the brain have to be comparable between centres to generate a comprehensive data pool, e.g. for multicentre studies. Equipment-specific effects on quantitative evaluations and corresponding methods for compensation, however, have been insufficiently examined. Previous studies have shown that quantitative results may vary significantly according to the imaging equipment used, thereby affecting clinical interpretation of the data. The aim of this study was to determine correction factors for common camera/collimator combinations based on standardised measurements of an anthropomorphic 3D basal ganglia phantom to compensate for the effects of different SPECT camera/collimator equipment. The latter may serve as a model for human studies of the dopaminergic system.
The striatum and background chambers of a commercially available phantom (RSD Alderson) were filled with various( 123)I concentrations encompassing specific striatum/background ratios from 0.6 to 16.1. This setup was imaged with the following four camera/collimator combinations: Siemens Multispect 3 fitted with LEHR and( 123)I parallel-hole collimators, Siemens ECAM with LEHR parallel-hole collimators and Philips Prism 3,000 fitted with LEHR fanbeam collimators, using standardised protocols for acquisition and reconstruction. All scans were automatically co-registered to a SPECT template of the phantom and quantified using a 3D volume of interest (VOI) map based on a CT scan of the phantom. All striatal/background ratios calculated by SPECT were compared with the true ratios calculated from the measurements in a well counter. Regression analyses were performed and recovery correction factors between measured and true ratios determined.
The relation between true and measured ratios could be sufficiently described by a linear regression for each camera/collimator combination without relevant improvement when using second-order polynomial regression models. The recovery correction factors and standard errors were 2.04+/-0.04 for the Philips Prism 3,000, 2.67+/-0.03 for the Siemens Multispect 3/LEHR parallel-hole collimators, 2.15+/-0.03 for the Siemens Multispect 3/(123)I collimators and 2.81+/-0.03 for the Siemens ECAM. Percentage recovery ranged from 36% to 49%.
Measurements of a 3D basal ganglia phantom with various imaging devices revealed linear correlations between measured and true striatal/background ratios. Based on these findings, adjustment of quantitative results between different equipment seems possible, provided that acquisition, reconstruction and evaluation are adequately standardised. The use of identical evaluation methods in phantom and patient studies (comparable shape, size and location of the VOIs) might allow transfer of the calculated correction factors from phantom to studies of the dopaminergic system in patients.
European journal of nuclear medicine and molecular imaging 05/2006; 33(4):495-502. · 4.99 Impact Factor
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ABSTRACT: Single-photon emission computed tomography (SPECT) of striatal dopamine transporters (DAT) has been used to demonstrate presynaptic dopaminergic dysfunction and to monitor the progression of Parkinson's disease. In parkinsonian patients who were implanted with embryonic mesencephalic tissue in the striatum, positron emission tomography (PET) has shown an increase in striatal [(18)F]dopa uptake as an indicator of graft survival and striatal reinnervation. The aim of this study was to investigate two patients who had undergone bilateral intrastriatal transplantation of human embryonic mesencephalic tissue using SPECT and the (123)I-labelled DAT ligand N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (IPT).
Two patients were subjected to [(123)I]IPT SPECT according to a standardised protocol prospectively and repeatedly up to 8 years after transplantation.
From baseline to year 3 after transplantation, mean striatal DAT availability increased by a mean of 61% (93% and 29% in patients 1 and 2, respectively). It then remained relatively stable up to 8 years in patient 2, but increased further by another 77% of baseline values in patient 1. Clinically, both patients experienced a moderate improvement in motor performance but developed moderate (patient 2) to severe (patient 1) off-medication dyskinesias.
Our data indicate that DAT imaging using IPT and SPECT can be used to demonstrate graft survival following dopaminergic tissue implantation. Because SPECT with DAT ligands is widely available in the routine clinical setting, this methodology may be a useful alternative to [(18)F]dopa PET for repeated scanning of grafted parkinsonian patients. The relevance of the long-term increase in DAT binding for the development of off-medication dyskinesias remains to be elucidated further.
European journal of nuclear medicine and molecular imaging 05/2006; 33(4):407-11. · 4.99 Impact Factor
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ABSTRACT: The aim of the present study was to evaluate whether extended analyses of O-(2-18F-fluoroethyl)-L-tyrosine (FET) uptake kinetics provide results superior to those of standard tumor-to-background ratios in predicting tumor grade in patients with pretreated gliomas.
Dynamic 18F-FET PET studies (0-40 min after injection of 180 MBq of 18F-FET) were performed on 45 glioma patients with suspected tumor recurrence after multimodal treatment. For the standard method, tumoral maximal standardized uptake value (SUVmax) and the ratio to the background were derived from a summed image 20-40 min after injection. Dynamic data evaluation comprised several approaches: first, SUV within a 90% isocontour threshold (SUV90) and the respective ratio to the background calculated for each time frame between 5 and 40 min after injection; second, the time to peak analysis; and third, various parameters accounting for the individual time course of 18F-FET uptake. Results were correlated with the histopathologic findings of MRI/PET-guided stereotactic biopsies and were evaluated with respect to their discriminatory power to separate low- from high-grade tumors using receiver-operating characteristic (ROC) analyses.
The parameters taking into account the individual time course of 18F-FET uptake were able to differentiate low-grade from high-grade recurrent astrocytomas with high diagnostic accuracy, reaching the best differentiation with a sensitivity and specificity of 92% and an area under the ROC curve (AUC) of 0.94. For the other parameters, the respective values were considerably lower (time to peak: 85% sensitivity and 88% specificity; SUV90-to-background ratio for single-frame evaluation of the early-uptake phase: 100% sensitivity, 62% specificity, and 0.81 AUC). The lowest performance was provided by the standard method (SUVmax: 73% sensitivity, 54% specificity, and 0.60 AUC; SUVmax-to-background ratio: 62% sensitivity, 62% specificity, and 0.59 AUC). Time-activity curves (5-40 min after injection) slightly and steadily increased in tumor-free patients and in low-grade tumors, whereas high-grade tumors showed an early peak around 10-15 min after injection followed by a decrease.
This study has shown differences in the dynamics of 18F-FET uptake between recurrent low- and high-grade gliomas. Therefore, parameters addressing the different kinetic behaviors allow discrimination with high diagnostic power between these 2 prognostically different groups. Thus, the techniques introduced here are clearly superior to the yet most widely used standard method.
Journal of Nuclear Medicine 04/2006; 47(3):393-403. · 6.38 Impact Factor
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ABSTRACT: In general, striatal dopamine transporter (DAT) binding is assessed by use of data reconstructed by filtered backprojection (FBP). The aim of this study was to investigate whether the use of an iterative reconstruction algorithm (ordered-subset expectation maximization [OSEM]) may provide results comparable to or even better than those obtained by standard FBP.
In 50 patients with parkinsonian syndromes, SPECT scans were acquired 4 h after injection of 185 MBq of (123)I-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ((123)I-FP-CIT) by use of a triple-head gamma-camera fitted with low-energy, high-resolution fanbeam collimators. After reconstruction by FBP and OSEM, data were filtered with a Butterworth filter and corrected for attenuation. Patient studies were automatically fitted to a mean template with a corresponding 3-dimensional (3D) volume-of-interest map covering the striatum, caudate, and putamen as well as an occipital reference region to calculate specific DAT binding. In addition, studies with an anthropomorphic 3D striatal phantom were performed to mimic different pathologies.
Visual assessment of phantom and patient data suggested a better separation between the caudate and the putamen in studies reconstructed by OSEM than in those reconstructed by FBP. There was an excellent correlation between specific DAT binding assessed by OSEM and that assessed by FBP (R(2) values: striatum, 0.999; caudate, 0.998; putamen, 0.998). Mean specific striatal binding obtained by OSEM was approximately 6% lower than that obtained by FBP. In no case was diagnostic information from OSEM inferior to that from FBP.
Iterative reconstruction of (123)I-FP-CIT SPECT studies for the assessment of DAT is feasible in routine clinical practice. A close correlation between FBP and OSEM data suggested that the latter also allow reliable quantification of DAT binding. Because of a better separation between the caudate and the putamen in the visual evaluation, as suggested by phantom and patient studies, OSEM may even be considered the preferable approach.
Journal of Nuclear Medicine 12/2005; 46(11):1804-11. · 6.38 Impact Factor
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ABSTRACT: New treatment modalities are available for patients with glioma, which may lead to unspecific changes in posttherapeutic magnetic resonance imaging (MRI) findings. Differentiation between tumor- and therapy-associated contrast enhancement on MRI scans after treatment may be difficult. The aim of this study was to analyze the diagnostic value of O-(2-[F]fluoroethyl)-l-tyrosine (FET)-positron emission tomography (PET) and MRI in the detection of tumor recurrence in patients with glioma after radiotherapy, radiosurgery, or multimodal treatment.
The study included 36 patients with gliomas and neuroradiological diagnosis of tumor recurrence and 9 patients who had undergone radioimmunotherapy. Patients were consecutively treated between September 2001 and May 2003. A contemporary FET-PET investigation was performed in all patients. A tissue diagnosis was made for comparative analysis in all patients with progressive neuroradiological or clinical findings (32 of 45 patients). In patients with transient neuroradiological or clinical deterioration (13 of 45 patients), clinical follow-up was used to support or contradict the imaging-based diagnosis.
Tumor recurrence was documented in 31 of 45 patients, and 14 of 45 patients were tumor free. FET-PET and MRI revealed a correct diagnosis in 44 and 36 patients, respectively. The difference was statistically significant (P < 0.01). Concordant findings after MRI and FET-PET were documented in 37 patients and discordant findings in 8 patients. The difference was statistically significant (P < 0.01). Specificity of FET-PET was 92.9%, and sensitivity was 100% (in patients suspected of having recurrent tumor as revealed by MRI). Sensitivity of MRI was 93.5%, and specificity was 50% (P < 0.05).
For patients with gliomas undergoing multimodal treatment or various forms of irradiation, conventional follow-up with MRI is insufficient to distinguish between benign side effects of therapy and tumor recurrence. FET-PET is a powerful tool to improve the differential diagnosis in these patients.
Neurosurgery 10/2005; 57(3):505-11; discussion 505-11. · 2.79 Impact Factor
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ABSTRACT: We report findings obtained with positron emission tomography with fluorodeoxyglucose-F18 (FDG PET) as tracer in two patients with acute alcohol hallucinosis. In line with previous findings, both patients had a significant hypometabolism in the left relative to the right thalamus. When the second patient was retested after clinical recovery, FDG PET findings were normalized, suggesting the probable thalamic dysfunction to be a functional rather than a structural abnormality.
Psychiatry Research 09/2005; 139(3):259-62. · 2.52 Impact Factor
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ABSTRACT: A lack of standardized evaluation procedures for dopamine transporter (DAT) SPECT investigations impairs both intra- and interindividual comparisons as well as multicenter trials-for example, for assessment of disease progression or the response to various drug treatments. Therefore, the aim of this study was to evaluate a novel automated method, which has been specifically developed for a standardized quantification of N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT studies.
DAT binding ratios of 155 (123)I-FP-CIT SPECT studies in 14 control subjects and 141 patients referred to confirm or exclude a presynaptic dopaminergic deficit were determined manually and by a fully automated technique. The latter included coregistration of patient studies to an 123I-FP-CIT mean template of controls with specialized, nonrigid adjustment for variation in striatal location, followed by calculation of specific striatal DAT binding using a standardized 3-dimensional volume-of-interest (VOI) map. The map is based on a MR scan and covers the striatum (S), caudate (C), putamen (P), and an occipital reference region. The semiquantitative ratios of both methods were compared with the visual findings.
Excellent linear correlations were observed between manually and automatically determined results (S: r = 0.99; C: r = 0.99; P: r = 0.99; P < 0.001, respectively). Automated evaluations delivered highly reproducible and visually exact coregistrations. Individual variations in striatal anatomy (e.g., atrophy) were considered and VOI positions were corrected before quantification. Both the manual and the automated method showed identical accuracy in supporting the visual diagnoses.
In a large patient population, excellent agreement was observed between quantitative DAT results using a time-consuming, observer-dependent, conventional manual method and the objective, automated evaluation specifically developed for a standardized evaluation of 123I-FP-CIT SPECT studies. It is suggested that the novel automated technique may substantially facilitate both intra- and interindividual comparisons as well as multicenter trials.
Journal of Nuclear Medicine 07/2005; 46(7):1109-18. · 6.38 Impact Factor
