Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor.

BACKGROUND: Although the contrast-enhancing (CE) lesion on T1-weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T2-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden. METHODS: Fifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy. RESULTS: The Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data. CONCLUSIONS: The similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM.

CD44 mediates the catch-bond activated rolling of HEPG2Iso epithelial cancer cells on hyaluronan.

The attachment of cancer cells to the endothelium is an essential step during metastatic dissemination. The cell surface receptor CD44 is capable of binding to hyaluronan (HA) produced by tumor cells and by cells of the tumor microenvironment, including blood endothelial cells. Here, we investigated the role of CD44 in the interaction between the liver cancer cell line HepG2Iso and HA surfaces. The rolling interaction was quantitatively analyzed using a microfluidic shear force setup. It was found that rolling of the liver cancer cells on HA depends on CD44, which mediates a catch-bond interaction and thus a flow-induced rolling of the cells. Reduction of CD44 expression by means of siRNA, inhibition of the interaction of CD44 with HA by antibody blocking, and treatment with low molecular weight HA inhibited liver cancer cell rolling on HA-coated surfaces. The results not only clearly show the dependency of the shear-induced catch-bond interaction of HepG2Iso cells on CD44 and HA, but also for the first time demonstrate CD44-mediated rolling for epithelium-derived cells that are typically adherent.

Classification of the pre-settlement behaviour of barnacle cyprids.

Barnacle cyprids exhibit a complex swimming and exploratory behaviour on surfaces and settlement is a consequence of extensive surface probing and selection of suitable settlement sites. In this work, the behaviour of cyprids in their pre-settlement phase was studied by three-dimensional video stereoscopy. With this technique, three-dimensional trajectories were obtained that were quantitatively analysed. The velocity during vertical sinking of cyprids of Balanus amphitrite was used with a modified form of Stokes' law to calculate their mean body density. Furthermore, a classification of the swimming patterns allowed the extension of existing models describing cyprid locomotion and swimming behaviour. The patterns were characterized with respect to their occurrence, transition between patterns and their velocity distribution, and motions were identified that led to surface contacts. This analysis provides a classification framework, which can assist future attempts to identify behavioural responses of cyprids to specific settlement cues.

Barnacle cyprid motility and distribution in the water column as an indicator of the settlement-inhibiting potential of nontoxic antifouling chemistries.

Testing of new coatings to control fouling frequently involves single-species laboratory bioassays. Barnacle cyprids are among the most widely used model organisms in marine biofouling research, and surfaces that inhibit their settlement are considered to be promising candidates for new coating concepts. An analysis of motility parameters (mean velocity and swimming area coefficient) and distribution of cyprids of Balanus amphitrite in different swimming regions in the vicinity of model surfaces (self-assembled monolayers) is presented. The data are correlated with the settlement preferences of cyprids on these surfaces. Cyprids were predominantly found in interfacial regions and the transition frequencies between swimming regions of different depths were determined.

Swimming behavior of Pseudomonas aeruginosa studied by holographic 3D tracking.

Holographic 3D tracking was applied to record and analyze the swimming behavior of Pseudomonas aeruginosa. The obtained trajectories allow to qualitatively and quantitatively analyze the free swimming behavior of the bacterium. This can be classified into five distinct swimming patterns. In addition to the previously reported smooth and oscillatory swimming motions, three additional patterns are distinguished. We show that Pseudomonas aeruginosa performs helical movements which were so far only described for larger microorganisms. Occurrence of the swimming patterns was determined and transitions between the patterns were analyzed.

Hologram reconstruction corrected for measurements through layers with different refractive indices in digital in-line holographic microscopy.

Digital in-line holographic microscopy (DIHM) using point sources has been shown to be a versatile technique, especially for three-dimensional tracking of particles or microorganisms. However, the spherical source wave is altered when measurements are performed through layers with different refractive indices, such as water cuvettes. The situations where a layer of medium with a refractive index different than that of the predominant surrounding propagation medium (usually air) is situated behind or in front of the plane to be reconstructed are analyzed in detail, and a general approach for reconstruction under such circumstances is developed. The proposed refractive index correction is tested experimentally and compared to conventional reconstruction algorithms. Using 3D traces of swimming algal spores, the influence on the velocity calculation is also shown.