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Biomedical subjects

Rudi Dierckx

Publications and source records attributed to Rudi Dierckx.

At least 19 recordsLinked to original sources

Differences of cortical 5-HT2A receptor binding index with SPECT in subtypes of anorexia nervosa: relationship with personality traits?

OBJECTIVE: Using single photon emission computed tomography and the 5-HT2A receptor antagonist, 123I-5-I-R91150, we explored differences in 5-HT2A binding index in anorexia nervosa patients with and without bulimic features. We also searched for associations between temperament dimensions and cortical 5-HT2) binding. METHOD: About 9 restrictive and 7 bulimic anorexia nervosa patients were examined and cortical 123I-5-I-R91150 binding index values were compared between the two subgroups. Open explorative correlation analysis was used to examine any relationships between binding index values and temperament scores, as assessed with the Temperament and Character Inventory. RESULTS: 5-HT2A binding index was significantly reduced in the parietal cortex in bulimic anorexia nervosa patients in comparison with restrictive anorectics. Further, a positive correlation was documented between reward dependence and parietal 5-HT2A binding index across patients in the two subgroups. DISCUSSION: Restrictive anorexia nervosa patients differ from binging/purging anorexia nervosa patients on the basis of a reduced parietal 5-HT2A binding index in the latter. We speculate that the finding of a positive correlation between parietal 5-HT2A binding and reward dependence might reflect an association between these two variables, at least in anorexia nervosa patients.

Adolescent↗

Blunted prefrontal perfusion in depressed patients performing the Tower of London task.

Impairment of cognition is common in depression, and many tasks on which depressed patients are impaired are sensitive to frontal lobe dysfunction. Performance on the Tower of London (TOL) task, which includes setting up and maintaining multiple subgoals at the same time, has been shown to depend on intact prefrontal cortices. Single photon emission computed tomography (SPECT) with 99mTc-ethyl cysteinate dimer was used to compare cognitive activation in nine depressed patients and nine normal controls during performance of the TOL task. Planning times and accuracy were measured as performance parameters, and functional imaging data were analysed with statistical parametric mapping (SPM99) to determine significant voxel-wise differences in activation between the two groups. During activation, depressed patients were as accurate as controls but differed in that they spent more thinking time. These findings agree with the results of neuropsychological studies. Compared with the normal controls, depressed patients were characterized by a blunted perfusion response in the right middle frontal cortex [Brodmann area (BA) 6] and the left superior frontal gyrus (BA 9), and by increased perfusion in the right superior temporal gyrus (BA 21) and the insular cortex (BA 13). This study shows that a SPECT activation procedure using the TOL task under classical test conditions is feasible in depressed patients.

Adult↗

Brain perfusion SPECT in impulsivity-related personality disorders.

BACKGROUND: Impulsive 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). METHODS: A 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). RESULTS: There 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). CONCLUSIONS: Patients with BPD and ASPD who showed impulsive behaviour have diminished rCBF in areas of the right prefrontal and temporal cortex.

Adult↗

Changes in cerebellar blood flow after manipulation of the cervical spine using Technetium 99m-ethyl cysteinate dimer.

BACKGROUND: Cervical spine manipulation is one of the many interventions practiced by health professionals to treat musculoskeletal disorders of the cervical spine. Although serious consequences of manipulation have been documented, the incidence is thought to be rare. More frequently, there may be minor transient side effects after manipulation of the cervical spine, such as headache, dizziness, and nausea. One of the hypothesis is that these side effects are caused by ischemia in the areas perfused by the vertebral arteries. OBJECTIVE: The purpose of this study was to investigate whether manipulation of the cervical spine can influence blood flow in the brain. METHODS: Single photon emission computed tomography was used to examine changes in regional cerebral blood flow caused by cervical spine manipulation (CSM) performed by a physiotherapist to 15 volunteers, using a 1-day split-dose Technetium 99m-ethyl cysteinate dimer single photon emission computed tomography activation paradigm. RESULTS: One brain region was identified showing a decreased regional cerebral blood flow after manipulation. This region was situated in the anterior lobe of the left cerebellum (-42, -48, -24). CONCLUSIONS: These findings suggest that cerebellar hypoperfusion may occur after CSM. This could explain why certain people experience headache, dizziness, or nausea after CSM. Further investigation into patient symptoms in the presence of cerebellar hypoperfusion and the possible link of these findings with other adverse reactions are warranted.

Adult↗

Cognitive neuroactivation using SPECT and the Stroop Colored Word Test in patients with diffuse brain injury.

Psychomotor slowing in patients with diffuse brain injury frequently underlies impaired cognitive performance on neuropsychological tests, for example, the Stroop Colored Word test. The aim of the present study was to determine the neural basis associated with performance on the Stroop interference subtask in patients with diffuse brain injury. We hypothesized that patients would be slower than healthy controls, and that this would be associated with brain activations other than those seen in healthy subjects. Brain perfusion, using a split-dose activation paradigm with single photon emission tomography (SPECT) and the Stroop test, was assessed in 9 patients with diffuse brain injury. The Stroop interference score was calculated as a behavioral parameter, and functional imaging data were analyzed with statistical parametrical mapping (SPM99) to determine significant voxel-wise differences of activation between the control and the activation condition. Patients were impaired on the interference subtask of the Stroop test. Comparison of the SPECT data obtained during the activation condition with those obtained during the control condition by means of SPM showed significant activations in the left inferior parietal lobe, the right anterior cingulate extending into the right middle frontal gyrus and the right caudate, and the left posterior cingulate cortex. Patients with diffuse brain injury were slower than healthy controls on the interference subtask of the Stroop test, suggesting difficulty with resistance to distractions. This finding was associated with activation effects in posterior (mainly parietal) brain areas in addition with activation of previously observed anterior (mainly anterior cingulate) brain regions.

Adult↗

Radiolabeled annexin-V for monitoring treatment response in oncology.

Because of its potential to allow for noninvasive, repetitive, and selective in vivo identification of the site and extent of apoptotic cell death and for monitoring cell death kinetics without the need for invasive biopsy, radiolabeled annexin-V is of major clinical relevance. This paper reviews available preclinical and clinical data on radiolabeled annexin-V pertaining to the domain of monitoring response to radiotherapy and chemotherapy, focusing especially on advantages and drawbacks of the different labeling procedures for the radiolabeling of annexin-V.

Animals↗

Intraobserver, interobserver, and day-to-day reproducibility of quantitative 99mTc-HYNIC annexin-V imaging in head and neck carcinoma.

RATIONALE: For clinical application, a sufficient reproducibility of 99mTc-HYNIC annexin-V quantitative uptake measurements must be demonstrated to allow a study of cell-death changes induced by chemotherapy over time and intersubject. Thus, the aim of this study was to estimate the intra-, inter-, and day-to-day reproducibility of quantitative 99mTc-HYNIC annexin-V tumor uptake values in patients suffering from head and neck carcinomas. METHODS: Thirteen (13) patients suffering from clinically suspected, histologically confirmed squamous head and neck carcinomas were prospectively included in the study. All patients were scheduled to undergo a spiral computed tomography scan and two 99mTc-HYNIC annexin-V scintigraphies within 3-5 days from each other, referred to as day 1 and day 2 of scintigraphy. The percentage of uptake of the injected dose of 99mTc-HYNIC annexin-V in tumor lesions on scintigrams divided by the tumor volume, as derived from CT, was determined twice within an interval of 2 weeks by observer 1 and once by observer 2 on day 1 of scintigraphy and once on day 2 of scintigraphy by observer 1. RESULTS: The mean of the difference for the intra-, inter-, and day-to-day measurements were -3.4%, 2.4%, and -6%, respectively. No systematic bias was observed for the mean of the differences for the intra-, inter-, and day-to-day measurements. The respective confidence intervals for the mean of the differences of intra-, inter-, and day-to-day variability were -8.2%-1.4%, -2.9%-7.8%, and -14.7%-2.7%. CONCLUSION: The reproducibility of quantitative 99mTc-HYNIC annexin-V tumor uptake measurements using a manual method appears to be acceptable for clinical use.

Adult↗

Application of a neuropsychological activation probe with SPECT: the 'Tower of London' task in healthy volunteers.

BACKGROUND: Human planning is a complex mental process that may be evaluated by the 'Tower of London' (TOL) task, which includes setting up and maintaining multiple subgoals at the same time. Although positron emission tomography and functional magnetic resonance imaging have provided reliable data on the recruitment of a neural network engaged in planning tasks, the experimental settings of these studies cannot be applied in clinical conditions. Hence, this study reports on the TOL task under classical neuropsychological test conditions using single photon emission computed tomography (SPECT) activation in 10 healthy subjects. METHODS: Participants first performed a control task and then an activation task, i.e., the TOL planning task In the planning task, subjects were required to change, in the minimum number of moves possible, an initial arrangement of beads to match a goal arrangement. Subjects solved a set of eight TOL problems of increasing difficulty. A control task was designed such that it eliminates planning abilities, which is the process of interest. Planning times and accuracy were measured as performance parameters and functional imaging data were analysed with statistical parametric mapping (SPM99) to determine significant voxel-wise activations between the planning task and the control task. RESULTS: Both overall and for each difficulty level, measures of accuracy were within the normal range. Similar results were found for the overall thinking time and thinking times of each difficulty level. That is, performance of the healthy subjects during the TOL task replicated the typical pattern of results found with appropriate control samples in the literature. Also, activation of the right prefrontal cortex was consistent with other functional imaging results, thereby validating the use of the TOL task in a SPECT activation paradigm. CONCLUSIONS: Based on the present study it may be concluded that the close resemblance of the test conditions of the SPECT activation procedure with those of the TOL task in the investigation room constitutes a major advantage for future application of the SPECT activation procedure in clinical conditions.

Adult↗

99mTc-HYNIC Annexin-V imaging of primary head and neck carcinoma.

In this study, the potential of 99mTc-HYNIC Annexin-V scintigraphy to visualize primary head and neck carcinoma was assessed and compared with computed tomography (CT) findings and histology. Eighteen patients suspected of having primary head and neck carcinoma underwent a spiral CT scan and 99mTc-HYNIC Annexin-V scintigraphy within 1 week of each other, followed by resection of the suspected lesion. Results obtained by CT and scintigraphy were compared vs. histopathology. The diagnosis was primary head and neck carcinoma in 18 patients, accompanied by lymph node involvement in seven patients. 99mTc-HYNIC Annexin-V uptake was identified in five patients on planar images and in 17 patients on tomographic images (single-photon emission computed tomography, SPECT), corresponding to the pathological regions identified by CT. In the remaining patient, CT and 99mTc-HYNIC Annexin-V scintigraphy were false negative. In 11 patients, SPECT and CT scan were concordant, identifying all primary lesions and two sites of lymph node involvement. In the six remaining patients, CT and SPECT accurately identified the primary lesion, but were discordant with regard to the existence of lymph node involvement. In five of six patients, SPECT failed to identify lymph node involvement, whereas CT scan did not. In the remaining patient, CT scan was false positive for lymph node involvement, whereas SPECT was not. In this series, 99mTc-HYNIC Annexin-V allowed for the visualization of all primary head and neck tumours identified by CT scan, but failed to identify most of the sites of lymph node involvement.

Aged↗

Importance of receptor density in alpha radioimmunotherapy in B cell malignancies: an in-vitro study.

BACKGROUND: External beam radiotherapy and beta radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha emitters is attractive because of the high linear energy transfer (LET) and short path length, allowing higher tumour cell kill and lower toxicity to healthy tissues. AIM: To assess the binding of rituximab to samples of B cell chronic lymphocytic leukaemia (B-CLL) and splenic lymphoma with villous lymphocytes (SLVL), and to evaluate the induction of apoptosis by conventional therapies as well as with Bi conjugated to rituximab. METHOD: 213Bi was eluted from a 225Ac generator and conjugated to CD20 antibody (rituximab) with CHX-A''-DTPA as chelator. Binding assays with 213Bi-rituximab were correlated to antibody binding capacity obtained by flow cytometry. Apoptosis was scored by flow cytometric analyses of the cells stained with annexin V-FITC and 7-amino-actinomycin D. RESULTS: Binding of 213Bi-rituximab was significantly lower for B-CLL compared to SLVL samples (12+/-3 and 42+/-10 213Bi atoms per cell, respectively, at 370 kBq.ml(-1)). The induction of apoptosis did not differ significantly between the two groups (B-CLL and SLVL) after external gamma irradiation or treatment with methylprednisolone and fludarabine (17+/-12% and 18+/-11%; 23+/-14% and 21+/-12%; 9+/-9% and 11+/-8%, respectively; all results expressed as percentages of all cells). Rituximab conjugated or not to 213Bi induced significantly more apoptosis in SLVL (42+/-19% and 42+/-17%) compared to B-CLL samples (27+/-12% and 6+/-8%). CONCLUSION: Binding assays confirm that SLVL samples present more CD20 antigens compared to B-CLL samples. Conventional therapies such as fludarabine, methylprednisolone or external gamma irradiation induce similar responses in the two populations but SLVL samples present higher sensitivity towards 213Bi-rituximab. These data are in favour of alpha-RIT in SLVL patients.

Alpha Particles↗

Comparison of cortical 5-HT2A receptor binding in bulimia nervosa patients and healthy volunteers.

OBJECTIVE: Bulimia nervosa has been associated with alterations in central serotonergic (5-HT) function. This study investigated iodine-labeled 4-amino-N-[1-[3-(4-fluorophenoxy) propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide ((123)I-5-I-R91150) binding to the 5-HT(2A) receptor in the brain by using single photon emission computed tomography in acutely ill bulimia nervosa patients. METHOD: Cortical (123)I-5-I-R91150 binding in 10 normal-weight patients with bulimia nervosa, purging type, was compared with that of 11 healthy volunteers. RESULTS: The 5-HT(2A) binding index of the bulimia nervosa patients, with and without correction for age, was not significantly different from that of the comparison group. CONCLUSIONS: As a group, acutely ill bulimia nervosa patients cannot be discriminated from healthy subjects on the basis of cortical (123)I-5-I-R91150 binding to the 5-HT(2A) receptor.

Acute Disease↗

Statistical parametric mapping of (99m)Tc-ECD SPECT in idiopathic Parkinson's disease and multiple system atrophy with predominant parkinsonian features: correlation with clinical parameters.

UNLABELLED: Statistical parametric mapping was performed to investigate differences in regional cerebral blood flow (rCBF) between patients with idiopathic Parkinson's disease (IPD), patients with multiple system atrophy (MSA), and healthy volunteers. In addition, a voxel-based covariance analysis was performed with disease-specific parameters and clinical patient data such as disease duration, medication, and clinical subscores. METHODS: For this purpose, (99m)Tc-ethylcysteine dimer (ECD) SPECT was performed on 81 IPD patients (50 men, 31 women; age, 62.6 +/- 10.2 y), 15 MSA patients (9 men, 6 women; age, 61.5 +/- 9.2 y), and 44 age- and sex-matched healthy volunteers (27 men, 17 women; age, 59.2 +/- 11.9 y). RESULTS: Significant hypoperfusion was observed in IPD compared with healthy subjects in a symmetric subcortical-cortical network including the basal ganglia, thalami, prefrontal and lateral frontal cortex, and parietooccipital cortex (voxel P value P(height) < 0.001, corrected for multiple comparisons). For MSA, only symmetric hypoperfusion was seen in the putamen and thalamus with respect to healthy subjects and to IPD (P(height) < 0.01, corrected). Prolonged disease duration or higher Hoehn and Yahr stage results in hypoperfusion of the posterior associative cortex. There is a negative correlation between perfusion of the caudate heads and limbic system and the standardized dosage of dopamine agonists in the patients with PD, whereas for MSA a bilateral decrease in putamen activity was noted (P(height) < 0.001, uncorrected). Cognitive performance was positively correlated with limbic perfusion and inversely correlated with posterior associative cortical areas, but not with prefrontal regions. CONCLUSION: Voxel-based analysis of (99m)Tc-ECD perfusion SPECT shows detailed differences between IPD and MSA, which may be of use in the differentiation of both disease entities, and is able to elucidate cerebral perfusion correlates of disease severity, dopamine agonist medication, and cognitive performance.

Algorithms↗

(123)I-Labeled chitinase as specific radioligand for in vivo detection of fungal infections in mice.

UNLABELLED: Given the scarcity of diagnostic tools for invasive fungal infections, the aim of this project was to develop new, specific radiopharmaceuticals for diagnosis of fungal infections. Chitin, which is expressed in the fungal cell wall but is absent in mammalian and bacterial cells, represents a potentially selective target for development of tracers for fungal infections. ChiB_E144Q (ChiB = chitinase B) from Serratia marcescens was labeled with (123)I, and in vitro and in vivo studies were assessed. METHODS: (123)I labeling of ChiB_E144Q from S. marcescens by direct iodination was characterized by high-pressure liquid chromatography (HPLC), and stability was evaluated. The in vitro binding properties of the compound to living bacteria, Candida albicans, and Aspergillus fumigatus were examined. Scintigraphy was performed and in vivo characteristics were studied in mice with infected thigh muscles. RESULTS: An average radiochemical yield of 35% was obtained. Radiochemical purity was >97% with a stability of >24 h as determined by HPLC and instant thin-layer chromatography. The average specific activity of the noncarrier-free (123)I-chitinase was 9.25 MBq/ micro g of enzyme. Binding assays showed virtually no binding to Eschericha coli and Staphylococcus aureus, and 2.4 x 10(3) Bq per 1 x 10(7) cells for A. fumigatus and 3.0 x 10(3) Bq per 1 x 10(7) cells for C. albicans (P < 0.05). Binding of the tracer dropped to almost zero for organisms previously incubated with a 50-fold excess of unlabeled enzyme. At 24 h after injection, target-to-nontarget (T/NT) ratios in mice were 20.6 +/- 3.6 for C. albicans and 15.2 +/- 3.7 for A. fumigatus infections, respectively, whereas T/NT ratios for S. aureus -and E. coli-infected thigh muscles or thigh muscles with a sterile inflammation did not exceed 4.9 +/- 2.6, 3.0 +/- 2.3, and 5.3 +/- 2.8, respectively (P < 0.05). Target-to-blood ratios for fungus-infected thighs were always >1. CONCLUSION: Our results show that (123)I-ChiB_E144Q has affinity in vitro for fungi. In vivo, the tracer accumulates in tissue infected with C. albicans and A. fumigatus but not in tissue infected with gram-positive or gram-negative bacteria, or in sterile inflammations, proving it to be a valuable SPECT diagnostic.

Animals↗

Synthesis and comparison of 99mTc-enrofloxacin and 99mTc-ciprofloxacin.

UNLABELLED: The use of (99m)Tc-ciprofloxacin as a tracer for infection and inflammation has been examined and discussed in the literature extensively. Its alleged ability to discriminate between sterile inflammation and bacterial versus nonbacterial infections has led to an intense debate. Other labeled fluoroquinolones might offer better characteristics or may add to a better understanding of the working mechanism of (99m)Tc-ciprofloxacin. The rationale of this work was to determine possible differences in the use of 2 labeled quinolones--that is, (99m)Tc-ciprofloxacin and (99m)Tc-enrofloxacin--as tracers for infection and inflammation in animals. METHODS: Ciprofloxacin and enrofloxacin were labeled with (99m)Tc and characterized. The stability of both preparations was evaluated in serum and in the presence of an excess of cysteine. In vitro binding studies were performed to determine the interaction of the labeled quinolones with bacteria and other cells. Rats with sterile and infectious intramuscular lesions were used to study the scintigraphic properties of the 2 compounds. To assess the specificity of binding to living bacteria, infectious intramuscular lesions of heat-killed Staphylococcus aureus and Candida albicans were used as controls. Imaging was performed with a gamma-camera at 0, 3, 5, and 22 h after injection. RESULTS: The radiochemical purity of both radiolabeled fluoroquinolones exceeded 95% as determined by instant thin-layer chromatography. Both compounds were moderately stable in serum. Binding assays did not show any saturable binding to S. aureus, heat-killed S. aureus, as well as C. albicans. None of the tracers showed specific binding to bacteria. Scintigraphy showed uptake in the infectious lesion at 1 h after injection, which washed out during the next 4 h. Abscess-to-muscle ratios for both preparations were not significantly different for the various infectious or inflammatory lesions studied and did not exceed an average of 4.25 +/- 0.62. CONCLUSION: The study demonstrated that (99m)Tc-ciprofloxacin and (99m)Tc-enrofloxacin do not show preferential binding to living bacteria. In vivo (99m)Tc-enrofloxacin has similar characteristics as (99m)Tc-ciprofloxacin except for differences in uptake in a few normal tissues.

Animals↗

The prefrontal cortex: insights from functional neuroimaging using cognitive activation tasks.

This review presents neuroimaging studies which have explored the functional anatomy of a variety of cognitive processes represented by the prefrontal cortex (PFC). Overall, these studies have demonstrated that standard prefrontal neuroactivation tasks recruit a widely distributed network within the brain of which the PFC consistently forms a part. As such, these results are in keeping with the notion that executive functions within the PFC rely not only on anterior (mainly prefrontal) brain areas, but also on posterior (mainly parietal) brain regions. Moreover, intervention of similar brain regions in a large number of different executive tasks suggests that higher-level cognitive functions may best be understood in terms of an interactive network of specialised anterior as well as posterior brain regions.

Animals↗