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Biomedical subjects

K Audenaert

Publications and source records attributed to K Audenaert.

At least 19 recordsLinked to original sources

Entanglement cost under positive-partial-transpose-preserving operations.

We study the entanglement cost under quantum operations preserving the positivity of the partial transpose (PPT operations). We demonstrate that this cost is directly related to the logarithmic negativity, thereby providing the operational interpretation for this entanglement measure. As examples we discuss general Werner states and arbitrary bipartite Gaussian states. Then we prove that for the antisymmetric Werner state PPT cost and PPT entanglement of distillation coincide. This is the first example of a truly mixed state for which entanglement manipulation is asymptotically reversible, which points towards a unique entanglement measure under PPT operations.

Journal Article↗

Biodistribution and displacement studies of the selective 5-HT2A receptor antagonist 123I-5-I-R91150 in the normal dog.

There is increasing interest in mapping receptors in vivo by using functional imaging modalities such as single photon emission tomography (SPET) and positron emission tomography (PET). Since SPET is a more accessible functional imaging modality than PET and, overall, it is more economical, radioligands suitable for this technique are in greater demand. Recently, 123I-5-I-R91150, a radioligand with high selectivity and affinity for 5-HT(2A) receptors in the brain, was introduced for SPET. This study reports on the whole-body distribution and brain uptake of the selective 123I-5-I-R91150 ligand in four normal dogs. The frontal to cerebellar ratio of uptake in time was determined in three dogs. Time-activity curve of venous blood was determined in one dog. Maximal global brain uptake was found at 10-60 min post-injection. Higher brain uptake was noted in the frontal cortical areas compared to the cerebellum. The frontal-cerebellar ratio reached the highest values at 90-180 min. Reversibility and pharmacological selectivity of ligand binding was demonstrated through displacement and blocking studies with the 5-HT(2A) receptor antagonist ketanserin. This study demonstrates that the specific 5-HT(2A) iodinated ligand can be used for imaging and semi-quantification of the 5-HT(2A) receptors in the canine brain in vivo by using SPET.

Animals↗

Asymptotic relative entropy of entanglement.

We present an analytical formula for the asymptotic relative entropy of entanglement with respect to positive partial transpose states for Werner states of arbitrary dimension. We then demonstrate its validity using methods from convex optimization. This is the first case in which the asymptotic value of a subadditive entanglement measure has been calculated.

Journal Article↗

Decreased frontal serotonin 5-HT 2a receptor binding index in deliberate self-harm patients.

Studies of serotonin metabolites in body fluids in attempted suicide patients and of post-mortem brain tissue of suicide victims have demonstrated the involvement of the serotonergic neurotransmission system in the pathogenesis of suicidal behaviour. Recently developed neuroimaging techniques offer the unique possibility of investigating in vivo the functional characteristics of this system. In this study the 5-HT2a receptor population of patients who had recently attempted suicide was studied by means of the highly specific radio-iodinated 5-HT2a receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy) propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide or 123I-5-I-R91150. Nine patients who had recently (1-7 days) attempted suicide and 12 age-matched healthy controls received an intravenous injection of 185 MBq 123I-5-I-R91150 and were scanned with high-resolution brain single-photon emission tomography (SPET). Stereotactic realigned images were analysed semi-quantitatively using predefined volumes of interest. Serotonin binding capacity was expressed as the ratio of specific to non-specific activity. The cerebellum was used as a measure of non-specific activity. An age-dependent 5-HT2a binding index was found, in agreement with previous literature. Deliberate self-harm patients had a significantly reduced mean frontal binding index after correction for age (P=0.002) when compared with controls. The reduction was more pronounced among deliberate self-injury patients (DSI) (P<0.001) than among deliberate self-poisoning patients (DSP). Frontal binding index was significantly lower in DSI patients than in DSP suicide attempters (P<0.001). It is concluded that brain SPET of the 5-HT2a serotonin receptor system in attempted suicide patients who are free of drugs influencing the serotonergic system shows in vivo evidence of a decreased frontal binding index of the 5-HT2a receptor, indicating a decrease in the number and/or in the binding affinity of 5-HT2a receptors.

Adolescent↗

99mTc-ECD brain perfusion SPET: variability, asymmetry and effects of age and gender in healthy adults.

Reliable and high-resolution reference data for regional cerebral blood flow measured with single-photon emission tomography (SPET) are necessary for optimal clinical and research use. Therefore, a large dataset of normal technetium-99m labelled ethylene cysteine dimer (ECD) perfusion SPET in carefully screened healthy volunteers with an age range spanning six decades was created, with correction for non-uniform attenuation and scatter and based on an anatomically standardised analysis. Eighty-nine healthy volunteers, stratified for gender (46 females, 43 males; age 20-81 years), were included. Twelve volunteers underwent repeated 99mTc-ECD SPET after 2.5+/-2.3 weeks. An automated whole-brain volume of interest analysis with MANOVA as well as voxelwise analysis using SPM99 was conducted. Average intersubject variability was 4.8% while intrasubject reproducibility was 3.0%. An age-related decline in tracer uptake was found in the anterior cingulate gyrus, bilateral basal ganglia, left prefrontal, left lateral frontal and left superior temporal and insular cortex (all P=0.001-0.02). There was an overall increase in right/left asymmetry with age, which was most pronounced in the frontal and temporal neocortex. The most significant correlations between AI and age decade were found in the prefrontal (R=0.35, P=0.001) and superior temporal neocortex (R=0.43, P<0.001). Women had significantly higher uptake in the right parietal cortex (P<0.001), while men showed higher uptake in the cerebellum and the left anterior temporal and orbitofrontal cortex (all P<0.01). This normative dataset allows age- and gender-specific patient and group assessment of 99mTc-ECD perfusion SPET under a wide variety of clinical circumstances in relation to normal variations and highlights the importance of both age- and gender-specific normal datasets for optimal analysis sensitivity.

Adult↗

In vivo evaluation of 4-[123I]iodo-N-[2[4-(6-trifluoromethyl-2-pyridinyl)-1-piperazinyl]ethyl]benzamide, a potential SPECT radioligand for the 5-HT1A receptor.

4-[123I]Iodo-N-[2-[4-(6-trifluoromethyl-2-pyridinyl)-1-piperazinyl]ethyl]benzamide (1.123I), a potential SPECT 5-HT(1A) radioligand, was evaluated in vivo in rats. Biodistribution studies were performed leading to a % ID in the brain of 0.22 at 5 min p.i. No significant differences in % ID/g tissue of the different isolated brain regions (hippocampus, hypothalamus, striatum, cortex and cerebellum) could be demonstrated. Blocking experiments with 8-OH-DPAT, WAY100635 and ketanserin could not show any significant change in tracer uptake in the isolated brain regions. These data suggest that uptake in the brain does not represent binding of 1.123I to the 5-HT(1A) receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

The classical stroop interference task as a prefrontal activation probe: a validation study using 99Tcm-ECD brain SPECT.

This study investigated the feasibility of brain single photon emission computed tomography (SPECT) functional imaging in a neuropsychological test setting, following a single-day protocol with a split-dose paradigm. The Stroop Color Word Test (SCWT) is an example of a well-documented prefrontal activation task. In a split-dose protocol, ten right-handed healthy volunteers were injected twice with 370 MBq 99Tcm-ethyl cysteinate dimer while performing consecutively both series of card-reading of the SCWT. Images were reconstructed using filtered back-projection and normalized to a standard template in Talairach coordinates. Statistical Parametric Mapping (SPM96) was used to determine voxelwise significant changes. A first activation cluster was found in the left medial prefrontal cortex, consisting of the gyrus cinguli anterior and the gyrus frontalis medius and superior. A second activation cluster included the right gyrus frontalis dorsalis and medius. These findings confirm to a large extent the results of previous functional magnetic resonance imaging, positron emission tomography studies of Stroop-like tasks. The choice and validity of various methodological characteristics of the experimental design leading to these results is critically discussed. It is concluded that brain SPECT activation with the Stroop Color Word Test under standard neuropsychological conditions in healthy volunteers, is both technically and practically feasible.

Adult↗

57Co SPECT, 99mTc-ECD SPECT, MRI and neuropsychological testing in senile dementia of the Alzheimer type.

Inflammatory mechanisms contribute to the pathophysiology of senile dementia of the Alzheimer type (sDAT). Previous studies have shown that 57Co single photon emission computed tomography (SPECT) is able to visualize inflammatory lesions, probably by means of the final common pathway of Ca2+ homeostasis disturbance in both neuronal degeneration and inflammation. The aims of this study were: (1) to detect 57Co SPECT changes in sDAT patients; (2) to correlate these findings with those of conventional neuroimaging techniques and neuropsychological testing (NPT); and (3) to compare 57Co SPECT findings in sDAT patients with those in other types of dementia. Six patients suffering from probable sDAT were included and compared with four patients suffering from other types of dementia. All patients had a magnetic resonance imaging (MRI) scan, NPT, 57Co and 99mTc-ethyl cysteinate dimer (ECD) SPECT scan. Perfusion SPECT images were semiquantitatively evaluated by comparison with an age-matched normal database, while 57Co SPECT scans were assessed qualitatively. MRI and 99mTc-ECD SPECT scans yielded conclusive results with regard to the exclusion of other pathologies and the confirmation of the diagnosis. Using visual analysis, 57Co SPECT scans were unable to show any regional raised uptake, irrespective of the disorder, depth or extent of the perfusion defects, presence of atrophy on MRI or the results of NPT.

Aged↗

Automated stereotactic standardization of brain SPECT receptor data using single-photon transmission images.

UNLABELLED: Intra- or intersubject registration of anatomically poorly defined SPECT data, such as in neuroreceptor imaging, is important for longitudinal or group analysis. However, accurate registration is difficult with only emission CT (ECT) data. We investigated fully automated registration using transmission CT (TCT) data as an intermediary image set. METHODS: The accuracy of TCT registration was compared to that of ECT registration for four types of data: gray-matter distribution (with [99mTc]ethylcysteinate dimer (ECD)), neocortical distribution (with [123I]R91150, a highly specific 5-HT2a receptor ligand), and striatal distribution of the D2-receptor ligand (with [123I]iodobenzamide (IBZM)) and the dopamine transporter ligand (with [123I]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CIT)). In total, 10 datasets of the various study types were used, all collected on a Toshiba GCA9300 gamma camera with super-high-resolution fanbeam collimators and 3 x 370 MBq of 153Gd transmission sources (4-min sequential TCT scanning for receptor studies and 20-min simultaneous scanning for [99mTc]ECD studies). Per dataset, 15 random misalignments of 9 rigid-body parameters (translation, rotation, and anisotropic scaling) were conducted. All coregistrations were done twice, both to the subject's original scan and to a study-specific template. This was done manually by two independent experienced observers and with three automated voxel similarity algorithms: mutual information (M.I.), count difference (C.D.), and uniformity index (U.I.). As an outcome measure, the impact of misregistration on semiquantification for the various study types was established. RESULTS: TCT matching allowed registration within 3.3 mm, 2.4 degrees, and 1.2% scaling (mean squared values for all directions) with an overall accuracy decrease in the following order: C.D. > M.I. > manual > U.I. For [99mTc]ECD and [123I]IBZM, TCT registration was as accurate as ECT registration, while it was far superior for the other receptor data types, especially for abnormal studies. The automated TCT registration accuracy corresponded to average quantification errors of 2.9% ([99mTc]ECD), 4.2% ([123I]BZM), 5.7% ([123I]R91150), and 6.1% ([123I]beta-CIT). CONCLUSION: Fully automated registration through intermediary TCT images is clinically feasible, fast, and accurate. In addition to nonuniform attenuation correction, TCT scanning therefore allows coregistration for group comparisons of SPECT receptor data on a standardized or pixel-by-pixel basis.

Adolescent↗

Assessing the performance of SPM analyses of spect neuroactivation studies. Statistical Parametric Mapping.

Several simulations of SPECT neuroactivation studies have been performed in order to determine the influence of both study size and activation focus characteristics on the detection of brain activation foci following a pixel-based statistical analysis. This was achieved by developing a methodology based on the Hoffman software brain phantom, SPECT acquisition simulation software, standard reconstruction software, and the Statistical Parametric Mapping (SPM96) package. We present results on the minimal activation levels required for focus detection. Furthermore, the improved sensitivity of the analysis resulting from the use of an iterative reconstruction technique (OSEM) with regard to the classical filtered backprojection (FBP) is assessed quantitatively, and the various physical, processing, and physiological parameters that potentially influence the detection of foci are discussed. Finally, the influence is investigated of the height threshold as implemented in SPM96 upon the size of the detected foci. Practical guidelines are proposed with regard to the number of subjects per group for SPECT activation studies following the split-dose design.

Brain↗

Verbal fluency as a prefrontal activation probe: a validation study using 99mTc-ECD brain SPET.

This study aimed to investigate the feasibility of brain single-photon emission tomography (SPET) in the letter and category fluency paradigm of the Controlled Oral Word Association (COWA) test in healthy volunteers. Two groups each comprising ten right-handed healthy volunteers were injected twice with 370 MBq technetium-99m ethyl cysteinate dimer following a split-dose paradigm (resting and activation condition). Statistical parametric mapping (SPM96) was used to determine voxelwise significant changes. The letter fluency and the category fluency activation paradigm had a differential brain activation pattern. The posterior part of the left inferior prefrontal cortex (LIPC) was activated in both paradigms, with the category fluency task having an extra activation in the anterior LIPC. In the category fluency task, but not the letter fluency task, an activation in the right inferior prefrontal cortex was found. These findings confirm to a large extent the results of previous functional magnetic resonance imaging and positron emission tomography studies in semantic and phonological activation paradigms. The choice and validity of various methodological characteristics of the experimental design leading to these results are critically discussed. It is concluded that brain SPET activation with the letter fluency and category fluency paradigm under standard neuropsychological conditions in healthy volunteers is both technically and practically feasible.

Adult↗

Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity.

BACKGROUND: According to recent theories, suicidal behaviour is associated with depressive disorders that are commonly induced by social stressors in persons with a trait-dependent vulnerability. Stressor-induced increased cortisol secretion may interfere with this vulnerability that can be defined in terms of (possibly inter-related) biological and psychological or personality-related characteristics. Delineation of such trait-like characteristics may increase the specificity in the prediction of suicidal behaviour and thus lead to new approaches to the treatment and prevention of suicidal behaviour. METHODS: Psychiatric symptomatology, personality dimensions (Cloninger's Temperament and Character), peripheral markers of serotonergic (whole blood serotonin, platelet MAO activity) and noradrenergic (plasma MHPG) activity, and urinary cortisol were measured in a random sample of patients with a history of violent suicidal behaviour and compared to those of patients without such a history. RESULTS: When compared to patients without a history of violent suicidal behaviour (n=23), patients with such a history (n=17) were characterised by higher urinary cortisol levels, a significantly lower mean score on Reward Dependence, a borderline significantly increased score on Novelty Seeking and a significantly lower mean plasma MHPG level. Urinary cortisol level correlated significantly with Reward Dependence and Novelty Seeking scores. There were no differences between patient groups regarding severity of anxiety or depressive symptomatology. No differences with regard to the biological parameters were found between patients who recently attempted suicide and those with a history of suicidal behaviour. LIMITATIONS: Limitations of this study included a relatively small number of study subjects and the use of peripheral markers to assess central neurotransmission functions. CONCLUSIONS: Violent suicidal behaviour is associated with increased cortisol secretion, a personality profile defined by low Reward Dependence (reflecting the degree of sensitivity to social stressors) and a tendency of increased Novelty Seeking (related to impulsivity and the regulation of anger), and reduced noradrenergic functioning (possibly reflecting an inability to adapt to stressors).

Adult↗

Validation of the cerebellum as a reference region for SPECT quantification in patients suffering from dementia of the Alzheimer type.

In longitudinal brain studies of dementia of the Alzheimer type (DAT), the cerebellum is often used as a reference region for single photon emission computed tomography (SPECT) quantification, which assumes no significant regional influence of physiological fluctuations or pathology. With the use of absolute quantification in DAT patients, reproducibility of cerebellar uptake of technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO) was tested and compared with the mean absolute cerebellar tracer uptake value in DAT patients and healthy control subjects. In 13 DAT patients SPECT studies were repeated within 2 weeks to assess reproducibility of cerebellar regional brain uptake (rBU). With calibrated point sources as scaling factors, cerebellar activity was expressed as rBU of HMPAO per cm3 brain tissue in percent of the injected lipophilic dose of 740 MBq (20 mCi). Also, mean cerebellar rBU in patients suffering from DAT was calculated and compared with a previously established database obtained in healthy volunteers. Repeated SPECT studies within a 2-week interval in clinically stable patients resulted in a mean rBU increase of 6.8 +/- 10.3% in the second SPECT study as compared with the first. A similar shift was previously reported in healthy volunteers. Mean cortical cerebellar rBU values in DAT patients and in the healthy reference population concurred, after cumulative corrections for body surface and for a mean brain volume of 1350 ml (obtained in healthy control subjects), showing respective mean values of 53.9 +/- 7.4 and of 52.0 +/- 7.3 x 10(-6) of the injected lipophilic dose 740 MBq (20 mCi) of HMPAO per cm3 of brain tissue. A unidirectional shift in mean absolute cerebellar uptake values occurs between repeat SPECT examinations in DAT patients similar to previous findings in a group of healthy volunteers. The origin of this phenomenon remains elusive but deserves further study with regard to SPECT (semi)quantification in DAT patients. Most interestingly, the presented findings suggest that with the use of HMPAO SPECT in DAT patients the cerebellum remains scintigraphically uninvolved.

Aged↗

Nanogram amounts of salicylic acid produced by the rhizobacterium Pseudomonas aeruginosa 7NSK2 activate the systemic acquired resistance pathway in bean.

Root colonization by specific nonpathogenic bacteria can induce a systemic resistance in plants to pathogen infections. In bean, this kind of systemic resistance can be induced by the rhizobacterium Pseudomonas aeruginosa 7NSK2 and depends on the production of salicylic acid by this strain. In a model with plants grown in perlite we demonstrated that Pseudomonas aeruginosa 7NSK2-induced resistance is equivalent to the inclusion of 1 nM salicylic acid in the nutrient solution and used the latter treatment to analyze the molecular basis of this phenomenon. Hydroponic feeding of 1 nM salicylic acid solutions induced phenylalanine ammonia-lyase activity in roots and increased free salicylic acid levels in leaves. Because pathogen-induced systemic acquired resistance involves similar changes it was concluded that 7NSK2-induced resistance is mediated by the systemic acquired resistance pathway. This conclusion was validated by analysis of phenylalanine ammonia-lyase activity in roots and of salicylic acid levels in leaves of soil-grown plants treated with Pseudomonas aeruginosa. The induction of systemic acquired resistance by nanogram amounts of salicylic acid is discussed with respect to long-distance signaling in systemic acquired resistance.

Fabaceae↗

Variability study of a non-invasive approach to the absolute quantification of cerebral blood flow with 99Tcm-ECD using aortic activity as the arterial input estimate.

The absolute measurement of regional cerebral blood flow can be made non-invasively if dynamic scanning is performed immediately following the intravenous injection of 99Tcm-labelled HMPAO or ECD. By application of an elementary one-step kinetic model in which the arterial input curve is estimated from a region of interest over the anterior aortic arch projection, a brain perfusion index (BPI) can be calculated which is correlated to the total hemispheric blood flow. The aim of this study was to assess the variability of the BPI approach as applied to the calculation of cerebral blood flow. For 46 patients (30 men, 16 women) aged 23.7-74.4 years (mean 60.3), we calculated hemispheric BPI factors. For two subgroups of 10 patients chosen at random, several data-processing parameters, including the number of noise suppression steps and the linear slope interval for the Patlak fit, were assessed. To determine the influence of region-of-interest selection and to estimate intra- and inter-observer differences, three independent observers conducted a repeat analysis of all 46 patients. From five patients who underwent the same injection procedure twice, an estimate of intra-subject reproducibility was calculated. Temporal noise reduction of the input data significantly decreased the intra-observer variability. Visual estimation of the linear interval in the Patlak curve is much less reproducible than automatic interval selection; very high interval borders in particular significantly decrease the calculated BPI. The intra-observer coefficients of variation for the BPI were 5.3, 5.6 and 7.9% respectively, corresponding to 2.8, 3.0 and 4.1% when converted to hemispheric CBF. The slight inter-observer differences found could be attributed to differing processing parameters. For the five patients in whom the procedure was repeated, the hemispheric BPI reproducibility index was on average 2.6%. Determination of absolute hemispheric blood flow can be performed in a precise manner by means of a dynamic scan during the first 2 min after tracer injection after careful optimization of the processing parameters.

Adult↗