Rudi Dierckx

Prefrontal 5-HT2a receptor binding index, hopelessness and personality characteristics in attempted suicide

BACKGROUNDnDepression, hopelessness, impaired problem solving capacities and deficient serotonergic functions have been identified as major causes of suicidal behaviour. In general, the relation between biological markers of attempted suicide and psychological functions has been investigated using indirect peripheral markers of, e.g. the serotonergic system. Recently, functional neuroimaging techniques with radioligands allow direct in vivo assessment of the neurobiological status of the central nervous system.nnnMETHODSnWe studied the binding index of serotonin-(2a) (5-HT(2a)) receptors in the frontal cortex of attempted suicide patients (n=9) and normal controls (n=13) using [123I]5-I-R91150, a highly selective 5-HT(2a) receptor ligand. Moreover, we measured personality characteristics (using Cloningers Temperament and Character Inventory) and levels of hopelessness (using Becks Hopelessness Scale), and studied the association between 5-HT(2a) receptor binding index, hopelessness and these personality dimensions.nnnRESULTSnWhen compared to normal controls, attempted suicide patients had a significantly lower binding potential of frontal 5-HT(2a) receptors, a higher level of hopelessness, a higher score on the temperament dimension harm avoidance and lower scores on the character dimensions self-directedness and cooperativeness. A significant correlation was found between harm avoidance, hopelessness and binding index in the population of patients that attempted suicide.nnnLIMITATIONSnThe limited number of patients and potential ingestion of psychotropic drugs may influence the results of the study.nnnCONCLUSIONSnLower central serotonergic function, hopelessness and harm avoidance are interrelated phenomena, which may increase the probability of the occurrence of attempted suicide.

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

Abstract. 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.

SPECT neuropsychological activation procedure with the Verbal Fluency Test in attempted suicide patients

Performance on the Verbal Fluency Test, as a measure of the ability of initiating processes, is reduced in depressed suicidal patients. The hampered results in this prefrontal executive task parallel the reduction in prefrontal blood perfusion and metabolism in depressed subjects. A neuropsychological activation study with the verbal fluency paradigm could evaluate a possible blunted increase in perfusion in the prefrontal cortex in depressed suicidal patients. Twenty clinically depressed patients who had recently attempted suicide and 20 healthy volunteers were included in a single photon emission computed tomography (SPECT) split-dose activation study following a verbal fluency paradigm. Statistical parametric mapping was used to determine voxelwise significant changes. Differences in regional cortical activation between the letter fluency and category fluency tasks in attempted suicide patients were found. These patients showed a blunted increase in perfusion in the prefrontal cortex. Methodological restrictions concerning group uniformity, medication bias and subjective effort of the participants are discussed. Our findings indicate a blunted increase in prefrontal blood perfusion as a possible biological reason for reduced drive and loss of initiative in attempted suicide patients.

Imaging of the 5-HT2A system: age-, gender-, and Alzheimer’s disease-related findings

Serotonin (5-HT) and more specifically the 5-HT(2A) receptor is involved in cognitive and non-cognitive behavior and plays an important role in Alzheimers disease (AD). The objective was to assess the 5-HT(2A) binding potential (BP) in healthy volunteers and AD with SPECT and 123I-5-I-R91150, a selective radio-iodinated 5-HT(2A) receptor antagonist. Twenty-six controls and nine AD patients were included. A semiquantitive analysis with normalization on cerebellar uptake provided estimates of BP for 26 cortical regions of interest. An age-related decline of neocortical BP was found (11.6% per decade). Compared to age-matched controls, a generally decreased neocortical BP in AD was found with a significant regional reduction in the orbitofrontal, prefrontal, lateral frontal, cingulate, sensorimotor, parietal inferior, and occipital region. These results are in line with previous postmortem, in vitro, and PET findings. The age-related decline highlights the necessity for matched advanced age study samples. The fact that the 5-HT(2A) receptor is differentially affected in AD patients has implications for both the etiological basis and therapeutic management of AD.

Brain perfusion SPECT in impulsivity-related personality disorders

BACKGROUNDnImpulsive behaviours in patients with cluster B personality disorders are associated with low glucose metabolism and regional cerebral blood flow in the frontal cortex and subcortical structures. The aim of this study is to confirm the presence of a particular pattern of brain perfusion in a sample of borderline (BPD) and anti-social personality disorder (ASPD) patients using brain perfusion single photon emission computed tomography (SPECT).nnnMETHODSnA brain perfusion SPECT study was performed in 37 patients with BPD or ASPD (and no Axis I diagnosis) and 34 healthy control participants. Data were acquired on a triple head Toshiba gamma camera. Scatter and attenuation correction was done. Reconstructed SPECT images were analyzed by Statistical Parametrical Mapping (SPM99).nnnRESULTSnThere were no significant differences in age and gender distributions between the patients and the healthy controls. With regard to the functional imaging results, patients were characterized by a reduced regional cerebral blood flow (rCBF) in right temporal and prefrontal brain areas, including the right lateral temporal cortex (BA 21), the right frontopolar cortex (BA 10) and the right ventrolateral prefontal cortex (BA 47).nnnCONCLUSIONSnPatients with BPD and ASPD who showed impulsive behaviour have diminished rCBF in areas of the right prefrontal and temporal cortex.

Experimental Performance Assessment of SPM for SPECT Neuroactivation Studies Using a Subresolution Sandwich Phantom Design

The validity domain of voxel-based statistical analysis of SPECT neuroactivation studies with statistical parametric mapping (SPM) has been investigated by a limited number of theoretical and simulation studies. In this work, an experimental setup is described with an assessment of its activation detection performance together with the influence of acquisition and processing parameters. A subresolution sandwich phantom was constructed using a printed high-resolution digital Hoffman phantom with a (99m)TcO(4)-ink mixture. Activations of 8, 16, and 24 mm diameter, with an intensity ranging from 5 to 60%, were constructed in the right frontal cortex, anterior and posterior cingulate, and left striatum. Triple-headed SPECT acquisitions were carried out using both fan-beam and parallel beam geometry. The impact of activation characteristics (size, intensity and location), study size, physical degradation factors, and reconstruction technique were studied using SPM99 in a group comparison design with correction for multiple comparisons. For a 15 x 15 design, all 24-mm activations of 5% intensity were detected for the fan-beam data. Decreased focus or study size, lower SPECT resolution, absence of scatter, and attenuation correction resulted in an increase in minimally detectable activation. For a single study referred to 15 control studies, only 24-mm activation foci with a minimal intensity of 10% were detected in the optimal configuration. This approach allows experimental parameter optimization of SPM-based group or single-subject SPECT activation studies compared to normal data, as used in clinical applications. In principle, these findings can be extended to SPECT receptor studies or PET data.

Effects of aging on brain perfusion and serotonin-2A receptor binding in the normal canine brain measured with single photon emission tomography

Normal aging is associated with a decrease in number and size of neurons, loss of synapses and neuronal branching and with a reduced functioning neurotransmitter systems, such as the serotonergic system. These structural and functional alterations have important impact on the behavioural, cognitive and affective status of the individual. With the introduction of functional brain imaging in veterinary medicine, the canine brain can be examined in vivo, evaluating changes in perfusion, metabolism and neurotransmitter systems. Since cognitive decline is recognised in the aging dog, it was our aim to investigate whether age related changes concerning cerebral perfusion and binding index of the selective 5-HT2A receptor ligand 123I-5-I-R91150 could be found in the canine brain. A group of twelve normal, aging dogs, older than 96 months, was compared to a normal reference group (n = 12), younger than 96 months. SPET images were obtained, using the radiopharmaceutical 99mTc-N,N-1,2-ethylene-diylbis-L-cysteine diethylester dihydrochloride (99mTc-ECD) for evaluation of the regional perfusion and the selective radioligand 123I-5-I-R91150 for visualization of the 5-HT2A receptor. Regional decrease of cerebral blood-flow was noted in the fronto- and temporocortical area and in the subcortical region. Age was negatively correlated with perfusion in the left and right fronto-cortical region. The binding index of the neuroreceptor radioligand was decreased in the fronto-cortical region, with a significant negative correlation with age in the right fronto-cortical area. No correlation was found between alteration of perfusion and binding index of the receptor ligand, suggesting that age related perfusion differences do not influence the binding of this radioligand. These results suggest that age related effects should be considered in functional canine brain imaging.

Transfer of normal 99mTc-ECD brain SPET databases between different gamma cameras

Abstract. A stereotactic, normal perfusion database is imperative for optimal clinical brain single-photon emission tomography (SPET). However, interdepartmental use of normal data necessitates accurate transferability of these data sets. The aim of this study was to investigate transfer of three normal perfusion databases obtained in the same large population of healthy volunteers who underwent sequential scanning using multihead gamma cameras with different resolution. Eighty-nine healthy adults (46 females, 43 males; aged 20–81 years) were thoroughly screened by history, biochemistry, physical and full neurological examination, neuropsychological testing and magnetic resonance imaging. After injection of 925xa0MBq technetium-99m labelled ethyl cysteinate dimer (ECD) under standard conditions, 101 scans were acquired from all subjects (12 repeat studies) on a triple-head Toshiba GCA-9300A (measured average FWHM 8.1xa0mm). Ninety-one sequential scans were performed on a dual-head Elscint Helix camera (FWHM 9.6xa0mm) and 22 subjects also underwent imaging on a triple-head Prism 3000 (FWHM 9.6xa0mm). Images were transferred to the same processing platform and reconstructed by filtered back-projection with the same Butterworth filter (order 8, cut-off 0.9 cycles/cm) and uniform Sorensen attenuation correction (µ=0.09). After automated rigid intrasubject registration, all subjects were automatically reoriented to a stereotactic template by a nine-parameter affine transformation. The databases were analysed using 35 predefined volumes of interest (VOIs) with normalisation on total VOI counts. For comparison, the high-resolution data were smoothed with a 3D Gaussian kernel to achieve more similar spatial resolution. Hoffman phantom measurements were conducted on all cameras. Partial volume effects after smoothing varied between –6.5% and 10%, depending on VOI size. Between-camera reproducibility was 2.5% and 2.7% for the Toshiba camera versus the Helix and the Prism database, respectively. The highest reduction in between-camera variability was achieved by resolution adjustment in combination with linear washout correction and a Hoffman phantom-based correction. In conclusion, transfer of normal perfusion data between multihead gamma cameras can be accurately achieved, thereby enabling widespread interdepartmental use, which is likely to have a positive impact on the diagnostic capabilities of clinical brain perfusion SPET.

MRI guided segmentation and quantification of SPECT images of the basal ganglia: a phantom study

Due to the limited resolution of single-photon emission computed tomography (SPECT) imaging devices, tissue interfaces are not well defined in the reconstructed image, even though resolution recovery techniques may be used during reconstruction. Therefore, segmentation of a particular region and quantification of the tracer uptake in that region is critical due to spillover effects, when based on the SPECT image only. In this study, we present two methods for quantification of tracer uptake in a SPECT image, defined by a matched high resolution structural magnetic resonance image. We show preliminary results of both techniques, when applied for quantifying regional uptake in the different compartments of a phantom simulating the basal ganglia. These results indicate that the quantification method, which takes into account the blurring by the SPECT imaging device, promises to be perform better in the presence of background activity.

Nuclear Medicine Imaging For Prediction or Early Assessment of Response to Chemotherapy in Patients Suffering From Breast Carcinoma

Reliable assays that could assess treatment response more rapidly or even predict responsiveness of breast tumours to chemotherapy would be very valuable as they would allow for adjustment of ineffective treatment and discontinuation of ineffective treatment in an early phase. As with effective cancer therapy, changes in tumour physiology, metabolism and proliferation do often precede volumetric changes routinely measured by morphological imaging modalities, for example, radiography and computerized tomography, assessment of these parameters by means of single photon emission computerized tomography (SPECT) or positron emission tomography may provide more sensitive and earlier markers of tumour cell death or growth inhibition. This paper reviews the available literature on the role of SPECT and PET in the measurement and visualisation of breast tumour metabolism (glucose utilization and protein synthesis rate), apoptosis induction and chemotherapy resistance mechanisms as predictors or early markers of tumour response or non-response to chemotherapeutic options in patients suffering from breast carcinoma.