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Hans Olsson

Publications and source records attributed to Hans Olsson.

18 recordsLinked to original sources
PubMed2006

Dopamine D2 receptor binding in drug-naïve patients with schizophrenia examined with raclopride-C11 and positron emission tomography.

The aim was to test the dopamine hypothesis of schizophrenia in a further analysis of D(2)-like dopamine binding using the radioligand [(11)C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D(2) binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D(2) BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D(2) BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D(2) BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D(2) BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [(11)C]FLB 457 and provide further support for a role of dopamine in the thalamus related to the pathophysiology of schizophrenia.

Adolescent↗
PubMed2006

A comparison of recent parametric neuroreceptor mapping approaches based on measurements with the high affinity PET radioligands [11C]FLB 457 and [11C]WAY 100635.

In positron emission tomography (PET) studies, the detailed mapping of neuroreceptor binding is a trade-off between parametric accuracy and spatial precision. Logan's graphical approach is a straightforward way to quickly obtain binding potential values at the voxel level but it has been shown to have a noise-dependent negative bias. More recently suggested approaches claim to improve parametric accuracy with retained spatial resolution. In the present study, we used PET measurements on regional D2 dopamine and 5-HT1A serotonin receptor binding in man to compare binding potential (BP) estimates of six different parametric imaging approaches to the traditional Logan ROI-based approach which was used as a "gold standard". The parametric imaging approaches included Logan's reference tissue graphical analysis (PILogan), its version recently modified by Varga and Szabo (PIVarga), two versions of the wavelet-based approach, Gunn's basis function method (BFM) and Gunn et al.'s recent compartmental theory-based approach employing basis pursuit strategy for kinetic modeling (called DEPICT). Applicability for practical purposes in basic and clinical research was also considered. The results indicate that the PILogan and PIVarga approaches fail to recover the correct values, the wavelet-based approaches overcome the noise susceptibility of the Logan fit with generally good recovery of BP values, and BFM and DEPICT seem to produce values with a bias dependent on receptor density. Further investigations on this bias and other phenomena revealed fundamental issues regarding the use of BFM and DEPICT on noisy voxel-wise data. In conclusion, the wavelet-based approaches seem to provide the most valid and reliable estimates across regions with a wide range of receptor densities. Furthermore, the results support the use of receptor parametric imaging in applied studies in basic or clinical research.

Algorithms↗
PubMed2006

Quantitative analyses of regional [11C]PE2I binding to the dopamine transporter in the human brain: a PET study.

PURPOSE: The dopamine transporter (DAT) is a plasma membrane protein of central interest in the pathophysiology of neuropsychiatric disorders and is known to be a target for psychostimulant drugs. [(11)C]PE2I is a new radioligand which binds selectively and with moderate affinity to central DAT, as has been demonstrated in vitro by autoradiography and in vivo by positron emission tomography (PET). The aims of the present PET study were to quantify regional [(11)C]PE2I binding to DAT in the human brain and to compare quantitative methods with regard to suitability for applied clinical studies. METHODS: One PET measurement was performed in each of eight healthy male subjects. The binding potential (BP) values were obtained by applying kinetic compartment analysis, which uses the metabolite-corrected arterial plasma curve as an input function. They were compared with the BP values quantified by two reference tissue approaches, using cerebellum as a reference region representing free and non-specific radioligand binding. RESULTS: The radioactivity concentration was highest in the striatum, lower in the midbrain and very low in the cerebellum. The regional [(11)C]PE2I binding could be interpreted by kinetic compartment models. However, the BP values in the striatum obtained by the compartment analyses were about 30% higher than the BP values obtained using reference tissue methods. We suggest that the difference may be explained by the inaccurate metabolite correction, small amounts of radioactive metabolites that could account for the presence of non-specific binding in the cerebellum and insufficient data acquisition time. CONCLUSION: The reference methods may be used to quantify [(11)C]PE2I binding in clinical studies, assuming that non-specific binding in the cerebellum does not vary between subjects and that an extended data acquisition time is employed. Moreover, the study corroborates the previous observation that [(11)C]PE2I is advantageous for PET examination of DAT binding in the midbrain, a region from which dopaminergic innervation originates and which is of central interest for the pathophysiology of several neuropsychiatric disorders.

Adult↗
PubMed2005

Quantification of 11C-MADAM binding to the serotonin transporter in the human brain.

UNLABELLED: (11)C-N,N-Dimethyl-2-(2-amino-4-methylphenylthio)benzylamine ((11)C-MADAM) is a newly synthesized radioligand with high selectivity and specificity for the serotonin transporter (5-HTT) in a monkey model. The purpose of this study in humans was to examine the suitability and potential of (11)C-MADAM for quantitative PET studies of 5-HTT in applied clinical studies on the pathophysiology and treatment of neuropsychiatric disorders. METHODS: PET examination was performed on each of 9 male subjects after intravenous injection of (11)C-MADAM with high specific radioactivity. Radioactive metabolites in plasma were determined with high-performance liquid chromatography. A metabolite-corrected arterial input function was used in kinetic 2- and 3-compartment analyses. Cerebellum was used as the reference region in a cross-validation of 6 reference tissue approaches. RESULTS: The highest radioactivity concentration was detected in the raphe nuclei, followed consecutively by the striatum, hippocampal complex, cingulate cortex, neocortex, and cerebellum. The time-activity curve for the fraction of unchanged (11)C-MADAM in plasma was best described by a sigmoid function. After 50 min, the fraction was 40%. The labeled metabolites were more polar than the mother compound. The compartment model approaches converged, and could describe the time-activity curves in all regions. The total volume of distribution (V(t)) was similar to the regional distribution volumes obtained by the linear graphic analysis. The binding potentials (BPs) for 6 different approaches yielded similar values in all regions but the raphe nuclei, where the 2 equilibrium methods provided lower values. CONCLUSION: The regional binding distribution of (11)C-MADAM is consistent with postmortem data acquired with (3)H-MADAM as well as with that of other reference ligands in vitro. The time-activity curves were well described by current major quantitative approaches. The suitability of the cerebellum as a reference region for nonspecific (11)C-MADAM binding could be confirmed, thus paving the way for experimentally less demanding approaches, such as the simplified reference tissue model, for applied clinical studies.

Adult↗
PubMed2004

Hepatocyte growth factor; expression, concentration and biological activity in chronic leg ulcers.

BACKGROUND: Hepatocyte growth factor (HGF) is a multifunctional cytokine that is involved in recovery process after organ injuries. OBJECTIVE: We studied HGF and the membrane bound receptor, c-met locally in patients who suffered from chronic leg ulcers (> or =1 year) caused by venous insufficiency. METHODS: Skin biopsies from the edge of the ulcers were taken from patients (n=13) and studied by immunohistochemical staining for detection of HGF and c-met. Skin biopsies from healthy volunteers (n=10) were used as the control material. Ulcer secretion from chronic ulcers (n=11) was examined for the presence of HGF by ELISA and the concentration of HGF was compared with acute ulcers in healthy controls (n=10) and in patients operated for a non-invasive breast cancer (n=12). RESULTS: We observed that c-met expression in the ulcer area increased significantly in chronic ulcers compared to controls (p=0.005). Concentration of ulcer-HGF in the patients with chronic ulcer was significantly higher than acute ulcers (p<0.01). The biological activity of HGF in ulcer secret was assessed in-vitro in transferred, mouse skin epithelial cell monolayer. Enhanced migration and morphologic changes were seen after adding ulcer secret from acute ulcers (> 1 ng/mL) that was inhibited by anti-HGF antibodies. No biological activity was observed by adding ulcer secret from chronic ulcers irrespective HGF concentration. CONCLUSION: We conclude that in chronic skin ulcers decreased biological activity of endogenous HGF and overexpression of c-met is seen which might explain fibrosis and delayed recovery. Administration of exogenous active HGF might contribute to accelerated healing in these patients.

Adult↗
PubMed2004

Differentiation of extrastriatal dopamine D2 receptor density and affinity in the human brain using PET.

Dopaminergic neurotransmission in extrastriatal regions may play a crucial role in the pathophysiology and treatment of neuropsychiatric disorders. The high-affinity radioligands [(11)C]FLB 457, [(123)I]epidepride, and [(18)F]fallypride are now used in clinical studies to measure these low-density receptor populations in vivo. However, a single determination of the regional binding potential (BP) does not differentiate receptor density (B(max)) from the apparent affinity (K(D)). In this positron emission tomography (PET) study, we measured extrastriatal dopamine D2 receptor density (B(max)) and apparent affinity (K(D)) in 10 healthy subjects using an in vivo saturation approach. Each subject participated in two to three PET measurements with different specific radioactivity of [(11)C]FLB 457. The commonly used simplified reference tissue model (SRTM) was used in a comparison of BP values with the B(max) values obtained from the saturation analysis. The calculated regional receptor density values were of the same magnitude (0.33-1.68 nM) and showed the same rank order as reported from postmortem studies, that is, in descending order thalamus, lateral temporal cortex, anterior cinguli, and frontal cortex. The affinity ranged from 0.27 to 0.43 nM, that is, approximately 10-20 times the value found in vitro (20 pM). The area under the cerebellar time activity curve (TAC) was slightly lower (11 +/- 8%, mean +/- SD, P = 0.004, n = 10) after injection of low as compared with high specific radioactivity, indicating sensitivity to the minute density of dopamine D2 receptors in the this region. The results of the present study support that dopamine D2 receptor density and affinity can be differentiated in low-density regions using a saturation approach. There was a significant (P < 0.001) correlation between the binding potential calculated with SRTM and the receptor density (B(max)), which supports the use of BP in clinical studies where differentiation of B(max) and K(D) is not required. In such studies, the mass of FLB 457 has to be less than 0.5 microg injected to avoid a mass effect of the radioligand itself.

Autoradiography↗
PubMed2003

Radioiodinated SB 207710 as a radioligand in vivo: imaging of brain 5-HT4 receptors with SPET.

Single-photon emission tomography (SPET) and positron emission tomography (PET), when coupled to suitable radioligands, are uniquely powerful for investigating the status of neurotransmitter receptors in vivo. The serotonin subtype-4 (5-HT(4)) receptor has discrete and very similar distributions in rodent and primate brain. This receptor population may play a role in normal cognition and memory and is perhaps perturbed in some neuropsychiatric disorders. SB 207710 [(1-butyl-4-piperidinylmethyl)-8-amino-7-iodo-1,4-benzodioxan-5-carboxylate] is a selective high-affinity antagonist at 5-HT(4) receptors. We explored radioiodinated SB 207710 as a possible radioligand for imaging 5-HT(4) receptors in vivo. Rats were injected intravenously with iodine-125 labelled SB 207710, euthanised at known times and dissected to establish radioactivity content in brain tissues. Radioactivity entered brain but cleared rapidly and to a high extent from blood and plasma. Between 45 and 75 min after injection, the ratios of radioactivity concentration in each of 12 selected brain tissues to that in receptor-poor cerebellum correlated with previous measures of 5-HT(4) receptor density distribution in vitro. The highest ratio was about 3.4 in striatum. SB 207710 was labelled with iodine-123 by an iododestannylation procedure. A cynomolgus monkey was injected intravenously with [(123)I]SB 207710 and examined by SPET. Maximal whole brain uptake of radioactivity was 2.3% of the injected dose at 18 min after radioligand injection. Brain images acquired between 9 and 90 min showed high radioactivity uptake in 5-HT(4) receptor-rich regions, such as striatum, and low uptake in receptor-poor cerebellum. At 169 min the ratio of radioactivity concentration in striatum to that in cerebellum was 4.0. In a second SPET experiment, the cynomolgus monkey was pretreated with a selective 5-HT(4) receptor antagonist, SB 204070, at 20 min before [(123)I]SB 207710 injection. Radioactivity in all brain regions was reduced almost to the level in cerebellum by 176 min after radioligand injection. These findings show that [(123)I]SB 207710 is an effective radioligand for imaging brain 5-HT(4) receptors in vivo.

Animals↗
PubMed2003

[(11)C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain.

The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2 E-enyl)-2beta-carbomethoxy-3beta-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [(11)C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/ microM). [(11)C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled beta-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [(11)C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [(11)C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [(11)C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man.

Adult↗
PubMed2003

Decreased thalamic D2/D3 receptor binding in drug-naive patients with schizophrenia: a PET study with [11C]FLB 457.

The thalamus is a neuroanatomic structure that has reciprocal connections with several brain regions suggested to be involved in the pathophysiology of schizophrenia. Recent studies have reported structural as well as functional abnormalities of the thalamus in schizophrenia. The aim of the present exploratory study was to examine D2/D3 dopamine receptors in the thalamus as well as the anterior cingulate and the frontal and temporal cortices by using the high-affinity radioligand [11C]FLB 457 and positron emission tomography (3D PET) and to explore the data in relation to disease, age and psychopathology. Nine drug-naive patients with schizophrenia and eight control subjects were examined. Regional binding potential (BP) values were calculated using the simplified reference tissue model. The D2/D3 receptor binding was significantly lower in the right medial thalamus in the schizophrenia patients compared to control subjects. In addition, we found a significant negative age effect on the D2/D3 BP in the frontal and temporal cortex for both groups. There was no significant age effect on the D2/D3 BP in the thalamus or in the anterior cingulate. The result provides additional support to the view that the age effect on D2/D3 receptors differ between brain regions. The preliminary finding of low thalamic D2/D3 BP in patients strengthens the hypothesis that the thalamus is a key region in the pathophysiology of schizophrenia.

Adult↗
PubMed2002

Low striatal and extra-striatal D2 receptor occupancy during treatment with the atypical antipsychotic sertindole.

RATIONALE: Sertindole is a new atypical antipsychotic drug. Preclinical pharmacology suggests that sertindole has a preferential effect on the activity of limbic and cortical dopaminergic neurons. Clinical trials have shown antipsychotic efficacy and very few extrapyramidal symptoms (EPS) with sertindole at 20 mg/day. OBJECTIVES: This positron emission tomography (PET) study aimed to measure D(2) receptor occupancy in striatal and extra-striatal regions induced by clinically representative doses of sertindole in patients with schizophrenia. METHOD: Four stabilized schizophrenic out-patients received sertindole 20 mg/day for 6-8 weeks. PET was performed using [(11)C]raclopride to measure D(2) receptor occupancy in the striatum and [(11)C]FLB457 to measure occupancy in the neocortex and thalamus, i.e. regions with very low D(2) receptor density. RESULTS: Striatal D(2) receptor occupancy was 52-68%. Similar occupancies were found in the thalamus, and the temporal and frontal cortices. CONCLUSIONS: Sertindole appears efficacious at a low D(2) receptor occupancy, comparable to that produced by clozapine. This finding could explain the low risk of EPS. The functional limbic selectivity of sertindole was not reflected in regional differences in receptor occupancy.

Adult↗
PubMed2002

Wavelet-aided parametric mapping of cerebral dopamine D2 receptors using the high affinity PET radioligand [11C]FLB 457.

The study of human neuroreceptor systems by means of positron emission tomography (PET) and suitable radioligands has proven to be of great importance in research on normal brain functions and the pathophysiology and treatment of neuropsychiatric disorders. A for long identified goal is to produce detailed parametric maps of showing neuroreceptor binding parameters for the entire human brain in vivo. The application of wavelet filters has recently been proposed as a solution to handle the inherently low signal-to-noise ratio of PET images. In the present study we applied the wavelet approach to data obtained from 10 healthy subjects who were examined with [11C]FLB 457. This high affinity dopamine D2-receptor antagonist provides a signal from a range of regions with a hundredfold difference in receptor density and should thus be suitable for evaluation of the wavelet approach. For cross-validation purposes the data were analysed with four methods: a traditional region-of-interest (ROI) based analysis, a pixel-based analysis and two variants of wavelet-aided analyses. In both variants the wavelet filter was spatially applied, but a two-dimensional filter was used in one case and a three-dimensional one in the other. The same linear-graphical binding potential (BP) estimation step was used for all methods and the results of the three parametric mapping techniques were compared to the reference ROI-based method by calculating the average BP of representative ROIs. The pixel-based and the two-dimensional-wavelet-based methods yielded highly correlated but systematically lower values when compared to the reference ROI-based method. The approach utilising three-dimensional wavelet filters yielded BP maps with regional averages closely matching the values of the ROI-based method. The results show that the combination of three-dimensional spatial wavelet filtering with established parameter estimation procedures provides detailed, accurate maps of radioligand binding parameters. Such maps can be used for in inter-individual or multi-condition comparisons of binding parameters at subregional levels.

Adult↗
PubMed2002

Cerebral uptake of [ethyl-11C]vinpocetine and 1-[11C]ethanol in cynomolgous monkeys: a comparative preclinical PET study.

PET provides the potential to quantify the distribution of radiolabelled drugs in the human body. In cases when radiolabelled compounds undergo metabolic transformation after administration in vivo, it is necessary to examine the kinetics and distribution of both the labeled mother compound and labeled metabolites. The objective of this study was to assess the extent by which 11C-labeled ethanol, the product arising from the de-esterification of the neuroprotective drug vinpocetine (ethyl-apovincaminate), might contribute to the regional cerebral radioactivity measured by PET after the administration of [ethyl-11C]vinpocetine. In three cynomolgous monkeys PET measurements were made after intravenous bolus injection of both [11C]vinpocetine and 1-[11C]ethanol. There was a marked difference between the regional time-activity curves of [11C]ethanol and [11C]vinpocetine. The distribution pattern obtained with [11C]ethanol was similar to that observed with blood flow tracers such as [15O]water and [15O]butanol. The study shows that although [11C]ethanol may moderately contribute to the brain radioactivity distribution pattern of [11C]vinpocetine, the rapid degradation of [11C]ethanol makes it unlikely that the contribution of this metabolite is of importance. The distinct distribution patterns and kinetics of [11C]vinpocetine and [11C]ethanol also support the view, obtained from our previous observations, that vinpocetine may bind to specific sites in the monkey and human brain, especially in the thalamus.

Animals↗
PubMed2002

The PET radioligand [carbonyl-(11)C]desmethyl-WAY-100635 binds to 5-HT(1A) receptors and provides a higher radioactive signal than [carbonyl-(11)C]WAY-100635 in the human brain.

UNLABELLED: 5-Hydroxytryptamine (serotonin)-1A (5-HT(1A)) receptors are of key interest in research on the pathophysiology and treatment of psychiatric disorders. The PET radioligand [carbonyl-(11)C]WAY-100635 ((11)C-WAY), where WAY-100635 is (3)H-(N-(2-(1-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexane-carboxamide, is commonly used for quantitation of 5-HT(1A) receptors in the human brain. The aim of this PET study was to compare (11)C-WAY with the putative metabolite and selective radioligand [carbonyl-(11)C]desmethyl-WAY-100635 ((11)C-DWAY). METHODS: A PET examination was performed on each of 5 healthy male volunteers after intravenous injection of (11)C-WAY and (11)C-DWAY on separate occasions. Radioactive metabolites in plasma were determined with high-performance liquid chromatography. The plasma metabolite--corrected input function was used in a kinetic compartment analysis. The simplified reference tissue model and peak equilibrium method, using the cerebellum as reference region, was applied for comparison of data. RESULTS: For both radioligands, the highest radioactivity was observed in the neocortex and the raphe nuclei, whereas radioactivity was low in the cerebellum. The regional binding potentials were similar for the 2 radioligands. The brain uptake was more than 2-fold higher for (11)C-DWAY than for (11)C-WAY, in part because of higher delivery (first-order rate constant K(1), 0.38 vs. 0.16). The time--activity curves were well described by a 3-compartment model for all regions, whereas uptake in the cerebellum could not be described by a 2-compartment model, supporting the existence of kinetically distinguishable nonspecific binding in the cerebellum or radioactive metabolites in the brain for both radioligands. Both radioligands were rapidly metabolized, and <10% of the radioactivity in plasma represented unchanged (11)C-WAY or (11)C-DWAY at 10 min after injection. The metabolic pattern was similar for both radioligands, with the formation of radiolabeled cyclohexanecarboxylic acid and more polar components. For (11)C-WAY, small amounts of an additional labeled metabolite comigrated with reference desmethyl-WAY-100635. CONCLUSION: The advantages of (11)C-DWAY over (11)C-WAY for research on central 5-HT(1A) receptors is supported by a significantly higher radioactivity signal at equipotent doses, providing improved imaging statistics and advantages in biomathematic modeling and the preclusion of (11)C-DWAY as a metabolite interfering with PET measurements.

Adult↗
PubMed2002

Standardized angiographically guided over-dilatation of stents using high pressure technique optimize results without increasing risks.

BACKGROUND: Routine angio-guided stent deployment results in a relatively high restenosis rate, which is mostly due to stent sub-expansion. Several different intravascular ultrasound (IVUS) criteria for optimal stent deployment have been proposed. A minimal in-stent restenosis and a minimal in-stent lumen area of > or = 9 mm2 have been associated with low rates of restenosis and target lesion revascularization (TLR) at 6 months. The role of high-pressure stent deployment and/or upsizing the post-dilatation balloon has not yet been clarified. The aim of this study was to evaluate the possibility of achieving accepted IVUS criteria safely without IVUS guidance with the combination of high-pressure deployment and post-dilatation with a 0.25 mm oversized balloon. METHODS: Thirty-four stents (26 NIR, 3 AVE GFX, 3 ACS GFX, 1 Bard, 1 Jostent) were implanted in 30 patients until optimal angiographical results were obtained (< 10% residual stenosis visually). Forty percent of the patients had unstable angina pectoris, forty-four percent had complex lesions (B2 and C) and 29% were occlusions. Mean inflation pressure was 12.6 +/- 1.6 atm, mean stent diameter was 3.2+/- 0.4 mm and mean stent length was 15.1+/- 5.4 mm. Post-dilatation was performed with the same stent using a short (compared to the angiographic reference segment), 0.25 mm oversized Scimed Maxxum Energy 3.5 +/- 0.4 mm balloon using high pressure (16.1 +/- 1.7 atm) followed by an off-line IVUS examination of the stents. There was clinical follow-up for 1 year. Results in patients with single-vessel disease were compared with those of non-randomized controls, who were stented with high pressure but without over-dilatation. RESULTS: No stent achieved the nominal diameter, in spite of over-dilatation. Mean minimal stent diameter (MLD) according to IVUS was 2.9 +/- 0.4 mm (92% of the angiographic reference diameter). Mean minimal lumen area (MLA) was 7.7 +/- 2.2 mm2. An in-stent MLA > or = 90% of the distal reference segment (AVID criteria) and an MLA > or = 100% or > or = 90% of the smallest/average reference segment (MUSIC criteria) was found in 67% and 57%, respectively. MLA > or = 9 mm2 was achieved in 38%. All stents had good apposition and obtained a symmetry index > or = 0.7 mm. No acute perforations, dissections or other serious complications occurred during the over-dilatation. At 1 year, five patients had re-angina leading to a new coronary angiography; only 1 patient had a significant in-stent restenosis requiring re-PTCA. Compared to non-overdilated historical controls, the standardized over-dilatation seemed to give a larger MLD (3.0 +/- 0.4 mm vs. 2.7 +/- 0.4 mm; p = 0.03), more patients who fulfilled AVID criteria (70% vs. 32%; p = 0.048) and more stents with MLA > or = 9 mm2 (46% vs. 11%; p = 0.02). CONCLUSION: A standardized 0.25 mm over-dilatation of stents never achieved nominal stent size, but did improve lumen gain and was associated with low target vessel revascularization without adding complications to the routine stenting procedure.

Aged↗
PubMed2000

A PET study of

Several radiolabelled cocaine analogues have been proposed for brain imaging of the dopamine transporter in research on neuropsychiatric disorders and drug abuse. In a recent positron emission tomography (PET) study we labelled the cocaine analogue ß-CIT-FE with carbon-11 and demonstrated high specific binding in the monkey striatum. In the present study, the selectivity of [11C]ß-CIT-FE binding in the primate brain was examined by pretreatment experiments with reference ligands for the dopamine, serotonin and norepinephrine transporter. In three healthy human subjects the regional binding of [11C]ß-CIT-FE was analysed using equilibrium and kinetic analyses. A Scatchard analysis showed that [11C]ß-CIT-FE bound in a saturable manner yielded a density value of the same order as that reported in vitro. The pharmacological characterization indicated that a high degree of [11C]-CIT-FE binding in the primate striatum represents the dopamine transporter. In human subjects the radioligand provided high brain uptake and reached peak equilibrium within 1 hour after i.v. injection. Different quantitative approaches gave similar values for the binding potential. The results support the view that [11C]ß-CIT-FE is a suitable radioligand for clinical studies of the dopamine transporter. In particular for studies requiring short data acquisition or repeated PET measurements on the same day.

Journal Article↗
PubMedDate not supplied

Angiography-guided routine coronary stent implantation results in suboptimal dilatation.

The resistance of the atherosclerotic lesion counteracts the expansion of the stent, resulting in suboptimal stent expansion. Intravascular ultrasound provides more precise information on stent expansion than coronary angiography but adds cost and time to the percutaneous transluminal coronary angiography procedure. The aim of this study was to evaluate the need for intravascular ultrasound at routine angiography-guided high pressure stent implantation by comparing stent expansion with predefined intracoronary ultrasound criteria for optimal stent implantation. In 32 patients, 48 stents (35 NIR, 12 AVE, and 1 Cordis) were implanted in A, B, and C stenoses using a high-pressure inflation technique until an optimal result was achieved according to angiography. Stent expansion was then evaluated by intravascular ultrasound as minimal lumen diameter, minimal lumen area, proximal and distal stent area, and a minimal lumen area symmetry index. These variables were then compared with the nominal stent size in vitro. Finally the stents were also evaluated with respect to the MUSIC criteria, ie, strict criteria regarding symmetry, apposition, and vessel geometry according to intravascular ultrasound after stent expansion. Forty-five stents could be completely analyzed. The mean balloon inflation pressure was 12.8 (range, 10-17) atm. The nominal stent size was not achieved in any patient. Minimal lumen diameter attained 77% and minimal lumen area 78% of expected nominal values (p<0.0001), distal stent area 88% (p < 0.001), and proximal stent area 92% (ns). Application of the MUSIC criteria showed that almost all stents (96%) had good stent apposition and symmetry index. Optimal proximal stent entrance was found in 70%. Optimal minimal lumen area in comparison to the reference areas was present in 41%. This lead to fulfilling of all MUSIC criteria in 47% of the stents. If nominal stent size had been achieved, symmetry index and apposition would have been fulfilled in all cases and optimal minimal lumen area increased to 75%. Acceptable proximal entrance however would have decreased to 55% and the fulfillment of all MUSIC criteria would increase only to 52%. In routine angiography-guided stent implantation in stenoses with a wide range of severities using modern stents and high pressure inflation technique to reach a visually optimal result, the nominal stent size was never achieved mainly due to residual intrastent stenosis. If nominal stent size had been achieved, the results would have improved only marginally and would still be suboptimal in almost half of the stents. These results highlight the shortcoming of angiography and the need for intravascular ultrasound in choosing correct stent size.

Aged↗