PET kinetics of radiolabeled antidepressant, [N-methyl-11C]mirtazapine, in the human brain

BACKGROUND: We compared six kinetic models with and without the requirement of arterial cannulation for estimating the binding potential of [N-methyl-(11)C]mirtazapine in the living human brain. METHODS: Distribution volumes of [N-methyl-(11)C]mirtazapine in brain regions were estimated using single- and two-tissue compartment models as well as a graphical plasma input model. The two-tissue compartment model provided a direct estimate of the binding potentials of [N-methyl-(11)C]mirtazapine in brain regions, while binding potentials of the single-tissue compartment model and the graphical plasma input model were estimated indirectly from ratios of distribution volumes in brain regions. We obtained also direct estimates of binding potentials using a graphical reference tissue model and two nonlinear reference tissue models. RESULTS: The two-tissue compartment model required several fits with different initial guesses for avoiding negative values of parameters. Despite the extra fits, estimates of distribution volumes and binding potentials of [N-methyl-(11)C]mirtazapine obtained by the two-tissue compartment model were far more variable than those produced by the other methods. The graphical plasma input method and the graphical reference tissue method provided estimates of the binding potential that correlated closely, but differed in magnitude. The single-tissue compartment model provided relatively low estimates of binding potentials with curves that failed to fit the data as well as the three other methods that used the entire series of positron emission tomography data. The reference tissue method and the simplified reference tissue method provided similar, consistent estimates of binding potentials. However, certain assumptions of the simplified reference tissue method may not be fulfilled by the radioligand. CONCLUSION: The reference tissue method is appropriate for estimating the binding potential of [N-methyl-(11)C]mirtazapine in regions of the human brain so that the binding potential of [N-methyl-(11)C]mirtazapine can be estimated without arterial cannulation

Fully-Automatic Multiresolution Idealization for Filtered Ion Channel Recordings: Flickering Event Detection

We propose a new model-free segmentation method, JULES, which combines recent statistical multiresolution techniques with local deconvolution for idealization of ion channel recordings. The multiresolution criterion takes into account scales down to the sampling rate enabling the detection of flickering events, i.e., events on small temporal scales, even below the filter frequency. For such small scales the deconvolution step allows for a precise determination of dwell times and, in particular, of amplitude levels, a task which is not possible with common thresholding methods. This is confirmed theoretically and in a comprehensive simulation study. In addition, JULES can be applied as a preprocessing method for a refined hidden Markov analysis. Our new methodolodgy allows us to show that gramicidin A flickering events have the same amplitude as the slow gating events. JULES is available as an R function jules in the package clampSeg

3D visualisering af trafik omkring ny letbane

I foråret 2005 tog Københavns Amt initiativ til en udstilling om den mulige kommende letbane på Ring 3. Til udstillingen leverede COWI dels en simulering af trafikken på og omkring letbanen, dels visualiseringer i form af billeder og videoer der viser trafikken i en detaljeret 3D-bymodel bl.a. med facader i form af digitalfotos fra området. Videoerne er del af den rejsende udstilling der i løbet af sommeren har været opstillet ved nogle af de fremtidige stoppesteder på ruten

Monitoring variables affecting positron emission tomography measurements of cerebral blood flow in anaesthetized pigs

Abstract Background Positron emission tomography (PET) imaging of anaesthetized pig brains is a useful tool in neuroscience. Stable cerebral blood flow (CBF) is essential for PET, since variations can affect the distribution of several radiotracers. However, the effect of physiological factors regulating CBF is unresolved and therefore knowledge of optimal anaesthesia and monitoring of pigs in PET studies is sparse. The aim of this study was therefore to determine if and how physiological variables and the duration of anaesthesia affected CBF as measured by PET using [15O]-water in isoflurane–N2O anaesthetized domestic female pigs. First, we examined how physiological monitoring parameters were associated with CBF, and which parameters should be monitored and if possible kept constant, during studies where a stable CBF is important. Secondly, we examined how the duration of anaesthesia affected CBF and the monitoring parameters. Results No significant statistical correlations were found between CBF and the nine monitoring variables. However, we found that arterial carbon dioxide tension (PaCO2) and body temperature were important predictors of CBF that should be observed and kept constant. In addition, we found that long-duration anaesthesia was significantly correlated with high heart rate, low arterial oxygen tension, and high body temperature, but not with CBF. Conclusions The findings indicate that PaCO2 and body temperature are crucial for maintaining stable levels of CBF and thus optimizing PET imaging of molecular mechanisms in the brain of anaesthetized pigs. Therefore, as a minimum these two variables should be monitored and kept constant. Furthermore, the duration of anaesthesia should be kept constant to avoid variations in monitoring variables

PET radioligand injection for pig neuroimaging

Pigs are useful models in neuroimaging studies with positron emission tomography (PET). Radiolabeled ligands are injected intravenously at the start of the scan and in pigs the most easily accessible route of administration is the ear vein. However, in brain studies the short distance between the brain and ear vein can be problematic as both are localized inside the field of view and, as a consequence, tracer residues in the catheter may influence the outcome of the scan. Here, we discuss options to avoid this problem. The femoral vein can be used in studies where repeated arterial blood sampling is needed because surgical incision has to be performed to allow access to the artery. When a non-invasive technique is preferred, the ear vein is a good alternative although it is recommended to dilute the tracer sufficiently in saline (20-50 mL) prior to injection. In addition, the tracer can be injected through an extension tube (filled with saline before injection), which is removed together with the syringe immediately after tracer injection. This avoids placing the syringe with tracer inside the PET gantry while injecting. By applying these simple techniques, it is our experience that it is possible to obtain high-quality images without exposing pigs to invasive procedures

CRIM-TRACK: Sensor system for detection of criminal chemical substances

Detection of illegal compounds requires a reliable, selective and sensitive detection device. The successful device features automated target acquisition, identification and signal processing. It is portable, fast, user friendly, sensitive, specific, and cost efficient. LEAs are in need of such technology. CRIM-TRACK is developing a sensing device based on these requirements. We engage highly skilled specialists from research institutions, industry, SMEs and LEAs and rely on a team of end users to benefit maximally from our prototypes. Currently we can detect minute quantities of drugs, explosives and precursors thereof in laboratory settings. Using colorimetric technology we have developed prototypes that employ disposable sensing chips. Ease of operation and intuitive sensor response are highly prioritized features that we implement as we gather data to feed into machine learning. With machine learning our ability to detect threat compounds amidst harmless substances improves. Different end users prefer their equipment optimized for their specific field. In an explosives-detecting scenario, the end user may prefer false positives over false negatives, while the opposite may be true in a drug-detecting scenario. Such decisions will be programmed to match user preference. Sensor output can be as detailed as the sensor allows. The user can be informed of the statistics behind the detection, identities of all detected substances, and quantities thereof. The response can also be simplified to “yes” vs. “no”. The technology under development in CRIM-TRACK will provide custom officers, police and other authorities with an effective tool to control trafficking of illegal drugs and drug precursors