Detection of areas with viable remnant tumor in postchemotherapy patients with Ewing's sarcoma by dynamic contrast-enhanced MRI using pharmacokinetic modeling

An approach is presented for monitoring the effects of neoadjuvant chemotherapy in patients with Ewing's sarcoma using dynamic contrast-enhanced perfusion magnetic resonance (MR) images. For that purpose, we modify the three-compartment pharmacokinetic permeability model introduced by Tofts et al. (Magn Reson Med 1991;17:357-67) to a two-compartment model. Perfusion MR images acquired using an intravenous injection with Gadolinium (Gd-DTPA) are analyzed with this two-compartment pharmacokinetic model as well as the with an extended pharmacokinetic model that includes the (local) arrival time t(0) of the tracer as an endogenous (estimated) parameter. For each MR section, a wash-in parameter associated with each voxel is estimated twice by fitting each of the two pharmacokinetic models to the dynamic MR signal. A comparison of the two wash-in parametric images (global versus local arrival time) with matched histologic macroslices demonstrates a good correspondence between areas with viable remnant tumor and a high wash-in rate. This can be explained by the high number and permeability of the (leaking) capillaries in viable tumor tissue. The novel pharmacokinetic model based on a local arrival time of tracer results in the best fit of the wash-in rate, the most important factor discerning viable from nonviable tumor components. However, parameter estimates obtained with this model are also more sensitive to noise in the MR signal. The novel pharmacokinetic model resulted in a sensitivity between 0.22 and 0.60 and a specificity between 0.61 and 1. The model based on a global arrival time gave sensitivities between 0.33 and 0.77 and specificities between 0.58 and 0.99. Both statistics are computed as the fraction of correctly labeled voxels (viable or nonviable tumor) within a specified ROI, which delineates the tumor. We conclude that the added value of estimating the local arrival time of tracer first manifests itself for moderate noise levels in the MR signal. The novel pharmacokinetic model should moreover be preferred when pharmacokinetic modeling is applied on the average signal intensity within a ROI, where noise has less effect on the fitted parameters.     

A density-based segmentation for 3D images,an application for X-ray micro-tomography

Density-based spatial clustering of applications with noise (DBSCAN) is an unsupervised classification algorithm which has been widely used in many areas with its simplicity and its ability to deal with hidden clusters of different sizes and shapes and with noise. However, the computational issue of the distance table and the non-stability in detecting the boundaries of adjacent clusters limit the application of the original algorithm to large datasets such as images. In this paper, the DBSCAN algorithm was revised and improved for image clustering and segmentation. The proposed clustering algorithm presents two major advantages over the original one. Firstly, the revised DBSCAN algorithm made it applicable for large 3D image dataset (often with millions of pixels) by using the coordinate system of the image data. Secondly, the revised algorithm solved the non-stability issue of boundary detection in the original DBSCAN. For broader applications, the image dataset can be ordinary 3D images or in general, it can also be a classification result of other type of image data e.g. a multivariate image.     

Determination of free clindamycin,flucloxacillin or tedizolid in plasma: Pay attention to physiological conditions when using ultrafiltration

Pharmacokinetic/pharmacodynamic indices of anti-infective drugs should be referenced to free drug concentrations. In the present study, clindamycin, flucloxacillin and tedizolid have been determined in human plasma by HPLC–UV. The drugs were separated isocratically within 3–6 min on a C₁₈ column using mixtures of phosphate buffer–acetonitrile of pH 7.1–7.2. Sample treatment for the determination of total drug concentrations in plasma included extraction/back-extraction (clindamycin) or protein precipitation (flucloxacillin, tedizolid). The free drug concentrations were determined after ultrafiltration. An ultrafiltration device with a membrane consisting of regenerated cellulose proved to be suitable for all drugs. Maintaining a physiological pH was crucial for clindamycin, whereas maintaining body temperature was essential for tedizolid. The methods were applied to the analysis of total and free drug concentrations in clinical samples and were sufficiently sensitive for pharmacokinetic studies and therapeutic drug monitoring.     

Spreeta-based biosensor immunoassays to detect fraudulent adulteration in milk and milk powder

Biacore biosensors (Biacore AB, Uppsala, Sweden) have proven to be robust analytical tools for the automated immunochemical detection of different adulterants and contaminants in milk and milk powder. However, the significant cost of the instruments is a disincentive for their wide application in food control laboratories. Therefore, a low-cost alternative optical biosensor (Spreeta, Texas Instruments, Attleboro, MA) was built into an affordable liquid handling system. Using this prototype biosensor, an inhibition immunoassay for bovine K-casein was evaluated for the detection of cow's milk in ewe's and goat's milk and for the detection of bovine rennet whey powder in milk powder. Comparable sensitivities were obtained for both adulterants in the Spreeta-based prototype biosensor and a Biacore 3000 instrument. The limit of detection for cow's milk was 0.17% (v/v) and bovine rennet whey powder could be detected in milk powder above 1% (w/w). The Spreeta sensor was also useful in the control of fraudulent water additions to milk, simply by measuring differences in the bulk response.     

A unified optical theorem for scalar and vectorial wave fields

The generalized optical theorem is an integral relation for the angle-dependent scattering amplitude of an inhomogeneous scattering object embedded in a homogeneous background. It has been derived separately for several scalar and vectorial wave phenomena. Here a unified optical theorem is derived that encompasses the separate versions for scalar and vectorial waves. Moreover, this unified theorem also holds for scattering by anisotropic elastic and piezoelectric scatterers as well as bianisotropic (non-reciprocal) EM scatterers.     

Radioreceptor assay — a tool for the bioanalysis of drugs

Radioreceptor assays can be developed for every class of drugs whose pharmacological action is mediated by a drug-receptor interaction. They provide a measure for biological activity which can be related to pharmacological effect.     

Improvement of selectivity and sensitivity by column switching in the determination of glycyrrhizin and glycyrrhetic acid in human plasma by high-performance liquid chromatography

A sensitive method is described for the simultaneous determination of glycyrrhizin and glycyrrhetic acid in human plasma. Quantitation is by high-performance liquid chromatography using ion-pair chromatography on a reversed-phase column. Variable-wavelength ultraviolet detection is employed. For the extraction of both compounds from plasma, a new solid-phase ion-pair extraction procedure using octadecylsilane columns was developed. Because of the strong forces involved in the protein binding of glycyrrhizin, quantitative extraction of this compound from plasma was possible only after an alkaline pH shift. A considerable improvement in selectivity and sensitivity was obtained by automated column switching involving on-line preseparation of the solid-phase extract on a short precolumn and chromatographic analysis of a heart-cut from the precolumn eluate. The limit of detection of both glycyrrhizin and glycyrrhetic acid was 0.1 mg/l in 0.5 ml of plasma. From a preliminary study in human volunteers, it was concluded that glycyrrhetic acid rather than glycyrrhizin is preferred in a study in human volunteers to assess the zero effect level of glycyrrhizin.