Influence of reconstruction settings in electrical impedance tomography on figures of merit and physiological parameters.

OBJECTIVE: Electrical impedance tomography (EIT) is a non-invasive and relatively cheap imaging technique allowing continuous monitoring of lung function at the bedside. However, image reconstruction and processing are not yet standardized for clinical use, limiting comparability and reproducibility between studies. In addition, optimal reconstruction settings still have to be identified for different clinical applications. In this work (i) a systematic way to select 'good' EIT algorithm parameters is developed and (ii) an evaluation of these parameters in terms of correct functional imaging and consistency is performed. APPROACH: First, 19 200 reconstruction models are generated by full factorial design of experiment in 5D space. Then, in order to quantify the quality of reconstruction, known conductivity changes are introduced and figures of merit (FoM) are calculated from the response image. These measures are further used to select a subset of reconstruction models, matching certain FoM thresholds, and are then used for in vivo evaluation. For this purpose, EIT images of one piglet are reconstructed to assess changes in tidal impedance and end-expiratory lung impedance, at positive end expiratory pressure of 0 and 15 cmH2O. From ground truth spirometry measurements, physiological criteria are formulated and the subset of models is further reduced. Finally, the remaining reconstruction models are evaluated on physiological data gathered from published data in the literature to assess the generalization possibilities. MAIN RESULTS: Parametrization of EIT image reconstruction has a strong influence on the resulting FoM and the derived physiological parameter. While numerous reconstruction models showed reasonable values for a single parameter, in total only 12 matched all simulation and physiological criteria. After validation on further physiological data, only a single reconstruction model remained with a noise figure of 0.3, target size of 0.08, weight radius of 0.3, normalized voltage and strong weighting of lung and heart regions. Furthermore, the relationship between the reconstruction settings and some FoM could be partly explained by using a linear statistical model. SIGNIFICANCE: The quest for standard reconstruction settings is highly relevant for future clinical applications. Simulation measures might help to assess the quality of the reconstruction models, but further evaluation of more data and different experimental settings is required.

Conformational analysis of spiro-epoxides by principal component analysis of molecular dynamics trajectories.

A new procedure for full conformational analyses comprising the statistical analysis of molecular dynamics trajectories was developed and applied. This method included a coordinate space for sampling using molecular dynamics simulations, reduction of dimensionality using tensor decomposition tools, determination of probability distributions in a reduced space, and finally the search for all of the strict extrema points of probability distributions. These extracted extrema points formed an initial guess for geometry optimization and clustering of conformers. A complete conformational space of 1-oxaspiro[2,5]octane and its cis- and trans-4-, 5- and 6-methyl substituted derivatives was also determined. In each case, eight conformers were found with two chair-like conformers predominant at room temperature. It was found that chair-like conformers with an epoxide ring oxygen atom in the pseudo-axial position had less strain, as well as all of their conformers with the methyl substituent in an equatorial position on a cyclohexane moiety.

Enantioselective formation and ring-opening of epoxides catalysed by halohydrin dehalogenases.

Halohydrin dehalogenases catalyse the conversion of vicinal halohydrins into their corresponding epoxides, while releasing halide ions. They can be found in several bacteria that use halogenated alcohols or compounds that are degraded via halohydrins as a carbon source for growth. Biochemical and structural studies have shown that halohydrin dehalogenases are evolutionarily and mechanistically related to enzymes of the SDR (short-chain dehydrogenase/reductase) superfamily. In the reverse reaction, which is epoxide-ring opening, different nucleophiles can be accepted, including azide, nitrite and cyanide. This remarkable catalytic promiscuity allows the enzymatic production of a broad range of beta-substituted alcohols from epoxides. In these oxirane-ring-opening reactions, the halohydrin dehalogenase from Agrobacterium radiobacter displays high enantioselectivity, making it possible to use the enzyme for the preparation of enantiopure building blocks for fine chemicals.