Biomedical subjects

Ronald Van Heertum

Publications and source records attributed to Ronald Van Heertum.

6 recordsLinked to original sources

PubMed2004

Striatal amphetamine-induced dopamine release in patients with schizotypal personality disorder studied with single photon emission computed tomography and [123I]iodobenzamide.

BACKGROUND: Previous imaging studies demonstrated that schizophrenia is associated with increased amphetamine-induced dopamine (DA) release in the striatum, most pronounced during episodes of illness exacerbation. Schizotypal personality disorder (SPD) is a schizophrenia spectrum disorder, genetically related to schizophrenia. The goal of this study was to investigate striatal DA function in patients with SPD. METHODS: In our study, 13 SPD patients and 13 matched healthy control subjects underwent single photon emission computed tomography (SPECT) scan during bolus plus constant infusion of the D2/3 radiotracer [123I]iodobenzamide (IBZM). Striatal specific to nonspecific equilibrium partition coefficient (V(3)") was measured at baseline and following amphetamine administration (.3 mg/kg). RESULTS: No significant differences were observed in baseline V(3)" between groups. Amphetamine induced a larger decrease in [123I]IBZM V(3)" in SPD patients (-12 +/- 5%) compared with control subjects (-7 +/- 5%, p =.03). CONCLUSIONS: The reduction in [123I]IBZM V(3)" induced by amphetamine in SPD was similar to that observed in remitted schizophrenia patients (-10 +/- 9%, n = 17), but significantly lower than that observed during illness exacerbation (-24 +/- 13%, n = 17). This suggests that DA dysregulation in schizophrenia spectrum disorders might have a trait component, present in remitted patients with schizophrenia and in SPD, and a state component, associated with psychotic exacerbations but not SPD.

Adult↗

PubMed2004

Comparative evaluation of serotonin transporter radioligands 11C-DASB and 11C-McN 5652 in healthy humans.

UNLABELLED: Alterations of serotonin transporters (SERT) are implicated in a large number of psychiatric conditions. (11)C-(+)-6beta-(4-Methylthiophenyl)-1,2,3,5,6alpha,10beta-hexahydropyrrolo[2,1-a]isoquinoline ((11)C-McN 5652) was the first PET radiotracer successfully developed as a SERT imaging agent. Recently, (11)C-3-amino-4-(2-dimethylaminomethylphenylthio)benzonitrile ((11)C-DASB) was introduced as an alternative to (11)C-McN 5652. Comparative evaluation of (11)C-DASB and (11)C-McN 5652 in baboons indicates that (11)C-DASB is associated with (a) lower nonspecific binding in the brain, (b) higher plasma free fraction, and (c) faster plasma clearance and brain uptake kinetics, enabling measurement of SERT parameters in a shorter scanning time. The purpose of this study was to compare these 2 agents in healthy humans. METHODS: Six healthy volunteers underwent 2 PET scans on the same day, one with (11)C-DASB and one with (11)C-McN 5652, in counterbalanced order. Regional distribution volumes (V(T)) were derived for 16 brain regions by kinetic analysis using the arterial input function. RESULTS: Both (11)C-DASB and (11)C-McN 5652 displayed similar patterns of accumulation: highest levels in the midbrain, thalamus and striatum; intermediate in the limbic regions; low in the neocortex; and lowest in the cerebellum. (11)C-DASB cerebellar V(T) (10.1 +/- 2.0 mL g(-1)) was lower than that of (11)C-McN 5652 (20.8 +/- 3.6 mL g(-1)), indicating lower nonspecific binding. As a result, regional specific-to-nonspecific equilibrium partition coefficients (V(3)") of (11)C-DASB were higher compared with those of (11)C-McN 5652 (for example, midbrain V(3)" of (11)C-DASB and (11)C-McN 5652 were 2.04 +/- 0.44 and 1.20 +/- 0.34, respectively). The plasma free fraction was 8.9% +/- 1.6% for (11)C-DASB and was not measurable for (11)C-McN 5652. In contrast to the situation observed in baboons, plasma clearances of both compounds were similar in humans, and the minimal scanning times required to derive time-invariant distribution volumes in all regions were comparable for both tracers (95 min). CONCLUSION: With the exception of the scanning time, predictions from baboon studies were confirmed in humans. The higher specific-to-nonspecific ratios of (11)C-DASB are a critical advantage. This property will be especially important for the measurement of SERT in regions with moderate density, such as the limbic regions, where alterations of serotonin transmission might be associated with anxiety and depression.

Adolescent↗

PubMed2003

Regional cerebral blood flow and cognitive deficits in chronic lyme disease.

This study examined brain functioning in patients with Lyme encephalopathy. Eleven patients underwent neuropsychological tests and Xenon(133)-regional cerebral blood flow (rCBF) studies, using an external detector system. Each rCBF scan was age- and sex-matched to two archival, normal controls. While few differences were noted on gray-matter flow indices (ISI, fg), Lyme patients demonstrated significant flow reductions in white matter index (k(2)) (p=.004), particularly in the posterior temporal and parietal lobes bilaterally (p=.003). Flow reductions in white matter areas were significantly associated with deficits in memory (r=.66, p=.027) and visuospatial organization (r=.62, p=.041). Results suggest that Lyme encephalopathy may be a disease primarily affecting the cerebral white matter.

Adult↗

PubMed2002

Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11]WAY-100635.

Serotonin (5-HT) 1A receptors have been implicated in a variety of conditions including, depression, suicidal behavior, and aggression. Post-mortem brain studies and in vivo imaging studies report a variety of age and sex effects on brain 5-HT(1A) binding. Behavioral data from 5-HT(1A) specific pharmacological challenges suggest a role for 5-HT(1A) receptors in aggression. The goal of the present study was to determine age, sex, and severity of life-time aggression effects on 5-HT(1A) binding potential (BP) in vivo using positron emission tomography (PET) and the high affinity 5-HT(1A) antagonist, [carbonyl-C-11]WAY-100635 in 12 healthy females (ages 41.0+/-15.7 years) and 13 healthy males (ages 39.6+/-15.5 years). Regions of interest included the dorsal raphe, anterior cingulate cortex, cingulate body, hippocampus, amygdala, medial prefrontal cortex (PFC), and orbital PFC. No significant correlation between age and BP was detected in any brain region. MANOVA of the first three principle components demonstrated a significantly higher BP in females compared with males (P=0.0127). Post-hoc tests confirmed sex differences (P<0.05) in the following regions: dorsal raphe, amygdala, anterior cingulate, cingulate body, medial PFC, and orbital PFC. The cerebellar volume of distribution was also significantly higher in females. There is a significant negative correlation between binding in several regions and lifetime aggression. We have replicated our post-mortem finding of higher 5-HT(1A) binding in females compared to males. We did not detect an age dependent decrease in binding in males or females. Lower 5-HT(1A) binding in more aggressive individuals is consistent with pharmacological challenge studies. Future studies should determine whether the binding is a state or trait effect.

Adult↗

PubMed2002

Prefrontal dopamine D1 receptors and working memory in schizophrenia.

Studies in nonhuman primates documented that appropriate stimulation of dopamine (DA) D1 receptors in the dorsolateral prefrontal cortex (DLPFC) is critical for working memory processing. The defective ability of patients with schizophrenia at working memory tasks is a core feature of this illness. It has been postulated that this impairment relates to a deficiency in mesocortical DA function. In this study, D1 receptor availability was measured with positron emission tomography and the selective D1 receptor antagonist [11C]NNC 112 in 16 patients with schizophrenia (seven drug-naive and nine drug-free patients) and 16 matched healthy controls. [11C]NNC 112 binding potential (BP) was significantly elevated in the DLPFC of patients with schizophrenia (1.63 +/- 0.39 ml/gm) compared with control subjects (1.27 +/- 0.44 ml/gm; p = 0.02). In patients with schizophrenia, increased DLPFC [11C]NNC 112 BP was a strong predictor of poor performance at the n-back task, a test of working memory. These findings confirm that alteration of DLPFC D1 receptor transmission is involved in working memory deficits presented by patients with schizophrenia. Increased D1 receptor availability observed in patients with schizophrenia might represent a compensatory (but ineffective) upregulation secondary to sustained deficiency in mesocortical DA function.

Adult↗

PubMed2002

Chest CT window settings with multiscale adaptive histogram equalization: pilot study.

Multiscale adaptive histogram equalization (MAHE), a wavelet-based algorithm, was investigated as a method of automatic simultaneous display of the full dynamic contrast range of a computed tomographic image. Interpretation times were significantly lower for MAHE-enhanced images compared with those for conventionally displayed images. Diagnostic accuracy, however, was insufficient in this pilot study to allow recommendation of MAHE as a replacement for conventional window display.

Algorithms↗