PubMed Health⌕ Search

Biomedical subjects

Alex Maes

Publications and source records attributed to Alex Maes.

9 recordsLinked to original sources

Recombinant P-selectin glycoprotein ligand-immunoglobulin, a P-selectin antagonist, as an adjunct to thrombolysis in acute myocardial infarction. The P-Selectin Antagonist Limiting Myonecrosis (PSALM) trial.

BACKGROUND: Inflammatory responses induced by reperfusion of previously ischemic myocardial tissue may lead to further damage of the microvascular structures. A group of cell adhesion molecules, named selectins, initiate those inflammatory changes at the endothelial wall surface. Recombinant P-selectin glycoprotein ligand-immunoglobulin (rPSGL-Ig), a P-selectin antagonist, was shown to have beneficial effects in several animal models of acute myocardial ischemia. We performed a mechanistic study with positron emission tomography to test the potential benefits of rPSGL-Ig in patients with ST-segment elevation acute myocardial infarction. METHODS: Patients with ST-elevation acute myocardial infarction presenting within the first 6 hours of onset of chest pain were enrolled. All patients received alteplase. Patients were randomly assigned in a 1:1:1 ratio to 3 treatment groups: placebo; 75 mg rPSGL-Ig; 150 mg rPSGL-Ig, given intravenously. Coronary angiography was performed 90 minutes after the start of thrombolytic therapy for TIMI flow grading. Myocardial blood flow (MBF) was measured with 13NH3 at rest and after adenosine administration on day 5. Myocardial blood flow at rest was measured again at day 30, followed by measurement of 18FDG uptake. In addition, a multigated acquisition, gated equilibrium blood pool study was performed at day 30. Continuous 12-lead electrocardiogram recording was performed during the first 24 hours. RESULTS: The trial was prematurely stopped by the sponsor for lack of efficacy in an accompanying larger trial after enrolling 88 patients in the current study. Median MBF in the infarct-related territory (expressed as percentage of the normalized blood flow) at day 5 was similar in the 3 treatment groups (9.1% in the placebo group vs 3.8% in the 75-mg dose and 4.3% in the 150-mg rPSGL-Ig treatment group; P = not significant). No significant differences in MBF reserve, myocardial metabolism, ST-segment resolution, left ventricular ejection fraction, or TIMI flow grade were found among the 3 groups. CONCLUSIONS: In this prematurely stopped mechanistic study, there was no evidence of a benefit of rPSGL-Ig given as an adjunct to thrombolysis on epicardial vessel patency, myocardial tissue reperfusion, or recovery of function.

Adolescent↗

Dual-tracer dopamine transporter and perfusion SPECT in differential diagnosis of parkinsonism using template-based discriminant analysis.

UNLABELLED: Clinical differential diagnosis in parkinsonism can be difficult especially at early stages. We investigated whether combined perfusion and dopamine transporter (DAT) imaging can aid in the differential diagnosis of parkinsonian disorders: idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), dementia with Lewy bodies (LBD), and essential tremor (ET). METHODS: One hundred twenty-nine patients were studied, retrospectively (69 males; 24 MSA, 12 PSP, 8 LBD, 27 ET, and 58 IPD; mean disease duration, 3.5 +/- 3.7 y). Diagnosis was based on established clinical criteria after follow-up of 5.5 +/- 3.8 y in a university specialist movement disorders clinic. Group characterization was done using a categoric voxel-based design and, second, a predefined volume-of-interest approach along Brodmann areas (BA) and subcortical structures, including striatal asymmetry and anteroposterior indices. Stepwise forward discriminant analysis was performed with cross-validation (CV) using the leave-one-out technique. RESULTS: Characteristic patterns for perfusion and DAT were found for all pathologies. In the parkinson-plus group, MSA, PSP, and LBD could be discriminated in 100% (+CV) of the cases. When including IPD, discrimination accuracy was 82.4% (99% without CV). 2beta-Carbomethoxy-3beta-(4-iodophenyl)nortropane imaging as a single technique was able to discriminate between ET and neurodegenerative forms with an accuracy of 93.0% (+CV); inclusion of perfusion information augmented this slightly to 97.4% (+CV). CONCLUSION: Dual-tracer DAT and perfusion SPECT in combination with discrimination analysis allows an automated, accurate differentiation between the most common forms of parkinsonism in a clinically relevant setting.

Algorithms↗

The value of (18)FDG-PET for the detection of infected hip prosthesis.

We compared the accuracy of fluorine-18 labelled 2-fluoro-2-deoxy- d-glucose positron emission tomography ((18)FDG PET) with that of technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy (LS) in the detection of infected hip prosthesis. Seventeen patients with a hip prosthesis suspected for infection were prospectively included and underwent (99m)Tc-methylene diphosphonate bone scintigraphy (BS), LS and an (18)FDG-PET scan within a 2-week period. Seven volunteers with ten asymptomatic hip prostheses were used as a control group and underwent BS and an (18)FDG-PET scan. Bacteriology of samples obtained by surgery or by needle aspiration and/or clinical follow-up for up to 6 months were used as the gold standard. Planar images of BS and LS (4 and 24 h p.i.) were acquired, followed by single-photon emission tomography (SPET) LS images (after 4 h). These images were scored as positive or negative by two experienced readers. The (18)FDG-PET scans of the patients were compared with the tracer distribution pattern in the asymptomatic control group and with BS. A phantom study was performed in order to identify artefacts. For this purpose, three different attenuation correction methods were tested. The combined analysis of the planar BS and LS resulted in a 75% sensitivity and a 78% specificity. The SPET LS images showed a better lesion contrast, resulting in an 88% sensitivity and a 100% specificity, while 24-h planar images were of no additional value. The analysis of PET images alone resulted in an 88% sensitivity and a 78% specificity. The combination of (18)FDG-PET and BS images resulted in an 88% sensitivity and a 67% specificity. Given the presence of small errors near the edge of the metal, which can induce significant artefacts in the corrected emission image, we decided to use the data without attenuation correction. In this preliminary study, (18)FDG-PET scans alone showed the same sensitivity as combined BS and LS, although the specificity was slightly lower.

Adult↗

Defining the transmurality of a chronic myocardial infarction by ultrasonic strain-rate imaging: implications for identifying intramural viability: an experimental study.

BACKGROUND: In a correlative functional/histopathologic study, we investigated the regional deformation characteristics of both chronic nontransmural and transmural infarctions before and after a dobutamine challenge. METHODS AND RESULTS: After stenosing copper-coated stent implantation to produce circumflex artery endothelial proliferation, 18 pigs were followed up for 5 weeks. Posteuthanasia histology showed 10 to have a nontransmural and 8 a transmural infarction. Eight nonstented animals served as controls. Regional radial function was monitored by measuring ultrasound-derived peak systolic strain rates (SR(SYS)) and systolic strains (epsilon(SYS)) (1) before stent implantation and (2) at 5 weeks, at baseline (bs) and during an incremental dobutamine infusion. In controls, dobutamine induced a linear increase in SR(SYS) (dobutamine: bs, 4.8+/-0.4 s(-1); 20 microg x kg(-1) x min(-1), 9.9+/-0.7 s(-1); P<0.0001) and an initial increase of epsilon(SYS) at low dose (bs, 58+/-5%; at 5 microg x kg(-1) x min(-1), 78+/-6%; P<0.05) but a subsequent decrease during higher infusion rates. In the nontransmural group, bs SR(SYS) and epsilon(SYS) were significantly lower than prestent values (SR(SYS), 2.9+/-0.5 s(-1) and epsilon(SYS), 32+/-6%, P<0.05 versus prestent). During dobutamine infusion, SR(SYS) increased slightly at 5 microg x kg(-1) x min(-1) (4.7+/-0.6 s(-1), P<0.05) but fell during higher infusion rates, whereas epsilon(SYS) showed no change. For nontransmural infarctions, transmural scar extension correlated closely with epsilon(SYS) at bs (r=0.88). For transmural infarctions, SR(SYS) at bs was significantly reduced and epsilon(SYS) was almost not measurable (SR(SYS), 1.8+/-0.3 s(-1); epsilon(SYS), 3+/-4%). Both deformation parameters showed no further change during the incremental dobutamine infusion. CONCLUSIONS: Ultrasonic deformation values could clearly differentiate chronic nontransmural from transmural myocardial infarction. The transmural extension of the scar could be defined by the regional deformation response.

Animals↗

Cardiac phantom measurement validating the methodology for a cardiac multi-centre trial with positron emission tomography.

In an ongoing international multi-centre trial, positron emission tomography (PET) is being used to evaluate the effect of a new P-selectin antagonist on the infarct size in patients with acute myocardial infarction, treated with thrombolysis. Although it is possible to correct for site-dependent factors, it is desirable to reduce these factors to a minimum. Therefore, acquisition and reconstruction protocols have been defined that can be closely followed by all participating centres. The resulting reconstructed images are transferred to the core centre for central processing with semi-automatic software. This paper reports on the multi-centre phantom experiment that was carried out to assess the inter-centre reproducibility of defect size determination with this protocol. Also, the spatial resolution of the short axis slices was examined. In addition, the analysis procedure was applied to normal PET studies to evaluate the specificity of perfusion defect detection. The transmural cold defect in the phantom occupied 14.8% of the left ventricular area. The automated analysis was applied to the phantom measurements from the 14 participating PET cameras. It yielded an accurate estimate of 15.1% with a standard deviation of 0.6%, indicating excellent reproducibility. The spatial resolution in the short axis slices was similar for all PET systems: 9.6+/-0.8 mm. The same procedure produced a defect size of zero in the studies of normal volunteers. This study indicates that cardiac studies from multiple PET systems can be pooled for statistical analysis.

Equipment Design↗

Clinical relevance of thyroid fluorodeoxyglucose-whole body positron emission tomography incidentaloma.

Fluorodeoxyglucose (FDG) whole body positron emission tomography (PET) scan is increasingly used in the diagnostic work-up or follow-up of patients. In these conditions, positive PET scans with unexpected hot spots within the thyroid region could be defined as thyroid FDG-PET incidentaloma (in analogy with unexpected sonographic thyroid nodules). We describe eight consecutive patients referred to the endocrine department because of thyroid "hot spots," incidentally detected by whole body FDG-PET scan (September 1999 to March 2001). Using ultrasound, fine needle aspiration cytology (FNAC), and histology reports, we tried to identify the pathology underlying thyroid FDG-PET incidentaloma. FNAC showed an indication for surgery in all patients. Surgery has been performed in 7 patients. Malignancy was correctly identified in five patients: two medullary thyroid carcinomas, one with lymph node invasion, and three papillary thyroid carcinomas with invasion through the thyroid capsule in two of the PTC cases. In two patients with a positive FDG-PET scan, FNAC pointed to follicular neoplasms, and final histology reports showed follicular adenoma. In the remaining patient, FNAC revealed a follicular lesion, but surgery has not yet been performed. In conclusion, a small series of consecutive thyroid FDG-PET incidentaloma cases is presented and suggests a high rate of clinically relevant malignancies.

Adenoma↗

A nonsurgical porcine model of left ventricular dysfunction. Validation of myocardial viability using dobutamine stress echocardiography and positron emission tomography.

BACKGROUND: Although several short-term animal models of stunning and hibernation have been studied extensively, it has been difficult to produce a consistent animal model of chronic hibernation. The aim of the present study was to develop a nonsurgical porcine stent model of coronary stenosis in order to investigate the relationship between chronic dysfunctional myocardium and viability using 2D-echo, dobutamine stress echo (DSE) and positron emission tomography (PET). METHODS AND RESULTS: Focal progressive coronary stenosis was induced by implantation of an oversized stent in the left anterior descending (LAD) and/or circumflex (LCX) coronary artery in a total of 115 pigs, according to various experimental protocols: copper stent in the LAD (group I, n = 5); noncoated stainless steel stent in the LAD combined with balloon overstretch (group II, n = 7); poly(organo)phosphazene-coated stent in the LAD (group III, n = 77); and poly(organo)phosphazene-coated stent in both the LAD and the LCX (group IV, n = 26). Occurrence of left ventricular dysfunction was evaluated weekly by 2D-echo. At the time of left ventricular dysfunction the presence of viable myocardium within the dysfunctional region was investigated with DSE and PET, and confirmed by histology. The degree of coronary artery stenosis was measured by quantitative coronary angiography and morphometry. Severe coronary artery stenosis in the presence of dysfunctional, but viable, myocardium was induced in groups III and IV (47% and 11% of the animals, respectively). CONCLUSIONS: The authors developed a nonsurgical porcine stent model of progressive coronary stenosis using an oversized polymer-coated stent resulting in chronically decreased myocardial function, with residual inotropic reserve and viable myocardium. This condition may arise from repetitive periods of ischemia, or from sustained hypoperfusion, or a combination of these processes eventually leading to myocardial hibernation.

Journal Article↗

Image-derived input function for [11C]flumazenil kinetic analysis in human brain.

PURPOSE: We describe a method for analysis of [11C]flumazenil data using an input curve directly derived from the positron emission tomography (PET) images. PROCEDURE: The shape of the tracer plasma curve was obtained from the product of the intact flumazenil fraction in plasma in six arterial samples and the internal carotid artery time-activity curve (TAC). The resulting curve was calibrated using the [11C]flumazenil concentration in three of the six samples. The curve peak was recovered by adding an exponential function to the scaled curve whose parameters were estimated from simultaneous fittings of several tissue TACs assuming that all regions share the same input. RESULTS: Good agreement was found between the image-derived and the experimental plasma curves in six subjects. Distribution volumes were highly correlated with linear regression slope and intercept values between [0.94, 1.03] and [-0.10, 0.16], respectively. CONCLUSION: The proposed method is suitable for benzodiazepine receptor quantification requiring only a few blood samples.

Brain↗