Koenraad Van Laere

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.

Acute single photon emission computed tomographic study of vagus nerve stimulation in refractory epilepsy

Summary: Purpose: Left‐sided vagus nerve stimulation (VNS) is an efficacious treatment for patients with refractory epilepsy. The precise mechanism of action remains to be elucidated. Only limited data on VNS‐induced changes in regional cerebral blood flow (rCBF) are available. The aim of this study was to investigate rCBF changes during initial VNS with single‐photon emission computed tomography (SPECT).

Regional Brain Activity during Different Paradigms of Mental Rotation in Healthy Volunteers: A Positron Emission Tomography Study

Positron emission tomography (PET) was used to observe changes in regional cerebral blood flow (rCBF) in 10 right-handed healthy volunteers performing two paradigms of mental rotation. In one paradigm, subjects mentally rotated a single alphanumeric stimulus to determine whether it was shown in a normal or mirror-image position. In a second paradigm, subjects mentally rotated and compared pairs of figurative stimuli to determine whether the stimuli were identical or mirror-images. In both paradigms, rCBF was compared with a control task that used identical stimuli, but required no mental rotation. Mental rotation of single alphanumeric stimuli engendered activation in the primary somatomotor area in the left precentral gyrus. Mental rotation of paired figures engendered activation in the left superior parietal lobule and the right frontal medial gyrus. A deactivated area was located in the medial part of the left superior frontal gyrus. Comparison of both paradigms revealed that the left gyrus precentralis was activated significantly during the alphanumeric condition and that the left gyrus lingualis was significantly activated during the paired figures condition. Motor processes may be an inherent part of every mental rotation but the type of motor involvement appears strongly dependent on the specific task or the specific stimuli. Similar paradigms, designed to isolate the same cognitive function, in the same subjects, using the same imaging technology and methodology, but differing only in stimulus material, lead to different areas of neural activation. Task specificity determines the most significant changes in cerebral blood flow in different mental rotation paradigms.

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.

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.

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.

Quantification of 99Tcm-HMPAO brain SPET in two series of healthy volunteers using different triple-headed SPET configurations : Normal databases and methodological considerations

We evaluated the methodological issues underlying the assessment of normal confidence intervals, as used in clinically based region-of-interest (ROI) semi-quantification of 99Tcm-HMPAO brain SPET. At two different centres equipped with high-resolution, triple-headed gamma cameras, HMPAO SPET scans were performed on two groups of 24 and 15 healthy volunteers respectively. Together with an operator-defined analysis (ODA), a semi-automated analysis (SAA) was conducted on the normal datasets in one centre. Tests of intra- and inter-observer variability were performed. Repeat scans were performed within 72 h after the first to analyse short-term regional inter-study variations. The overall regional uptake showed significant differences in most regions between both normal datasets. Intra-observer and inter-observer reproducibility were on average within 4% for the ODA, while for the SAA it was less than 1%. Inter-study variations were excellent for both centres, ranging from -4% to +3% for most regions studied. The variability in clinical brain perfusion studies largely depends on the reproducibility of the data analysis technique. A semi-automated approach shows clear advantages over an entirely operator-defined approach. Intra-subject repeat studies show enough stability for use as reliable baseline measurements in the construction of a normal database or to allow activation studies with high sensitivity.

Dopaminergic neurotransmission in psychiatry: should selection of patients only be based on DSM or ICD criteria?

Patients suffering from clearly distinct psychiatric disorders, such as affective or psychotic disorders, as defined by criteria suggested by the Diagnostic and Statistical Manual of Mental Disorders (DSM) [1] or the International Statistical Classification of Diseases (ICD) [2], show a considerable overlap in positive and negative symptomatology and neuropsychological performance [3, 4]. Both biochemical assessments of peripheral body fluids and post-mortem brain studies of patients with divergent psychiatric disorders indicate that the cluster of negative symptomatology (e.g. speech poverty, psychomotor slowing, affective flattening, loss of initiative and drive), which often dominates the clinical picture, is associated with a decreased dopaminergic function in the brain [5, 6]. On the other hand, several lines of evidence point to hyperactivity of the dopaminergic neurotransmitter system in the modulation of positive, psychotic symptoms (e.g. delusions and hallucinations) [7]. Over the past two decades, positron emission tomography (PET) and single-photon emission tomography (SPET) dopaminergic receptor imaging studies have been used to elucidate the existence of possible imbalances in dopaminergic transmission underlying different categorical DSM or ICD patient populations. The majority of these studies have focussed on schizophrenic patients and only a few have addressed patients with affective disorders. Overall results obtained by these studies are contradictory, partly due to the relatively small number of patients in the individual studies and differences in ligands and/or methods of quantification. However, such discrepancies in the results can largely be explained if more attention is paid to differences in patient symptomatology, rather than merely adopting a nosological approach by considering disease classification according to the DSM or ICD criteria.

Predictive value of 99Tcm-DTPA captopril scintigraphy in patients with a solitary kidney and reduced kidney function.

The aim of this study was to determine if the qualitative 99Tcm-DTPA captopril radionuclide test (CRT) can help predict the acute detrimental effect of angiotensin-converting enzyme (ACE) inhibitors on renal function in hypertensive patients with solitary kidneys and chronic renal failure. Between 1991 and 1996, eight consecutive patients (6 males, 2 females) aged 27-73 years (mean 49.8 years) with known chronic renal failure and a solitary kidney referred for ACE treatment were included. 99Tcm-DTPA renography was performed at baseline and 1 h after the administration of 25 mg captopril within 1 week of each other. The CRT was performed in accordance with the criteria of the Working Party on the Diagnostic Criteria of Renovascular Hypertension with Captopril Renography. A beneficial or detrimental effect of subsequent ACE inhibitor treatment on renal function was determined by long-term follow-up (> or = 2 years). The CRT accurately predicted outcome in all eight patients subsequently treated with ACE inhibitors. In conclusion, our results suggest a role for qualitative 99Tcm-DTPA CRT in the prediction of renal function in patients with a solitary kidney and chronic renal failure subsequently treated with ACE inhibitors.