Quantitative pharmacokinetic analysis of DCE-MRI data without an arterial input function: a reference region model

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumor perfusion, microvascular vessel wall permeability and extravascular-extracellular volume fraction. Analysis of DCE-MRI data is usually based on indicator dilution theory that requires knowledge of the concentration of the contrast agent in the blood plasma, the arterial input function (AIF). A method is presented that compares the tissues of interest (TOI) curve shape to that of a reference region (RR), thereby eliminating the need for direct AIF measurement. By assigning literature values for Ktrans (the blood perfusion-vessel permeability product) and v(e) (extravascular-extracellular volume fraction) in a reference tissue, it is possible to extract the Ktrans and v(e) values for a TOI without knowledge of the AIF. The operational RR equation for DCE-MRI analysis is derived, and its sensitivity to noise and incorrect assignment of the RR parameters is tested via simulations. The method is robust at noise levels of 10%, returning accurate (+/-20% in the worst case) and precise (+/-15% in the worst case) values. Errors in the TOI Ktrans and v(e) values scale approximately linearly with the errors in the assigned RR Ktrans and v(e) values. The methodology is then applied to a Lewis Lung Carcinoma mouse tumor model. A slowly enhancing TOI yielded Ktrans=0.039+/-0.002 min-1 and v(e)=0.46+/-0.01, while a rapidly enhancing region yielded Ktrans=0.35+/-0.05 min-1 and v(e)=0.31+/-0.01. Parametric Ktrans and v(e) mappings manifested a tumor periphery with elevated Ktrans (>0.30 min-1) and v(e) (>0.30) values. The main advantage of the RR approach is that it allows for quantitative assessment of tissue properties without having to obtain high temporal resolution images to characterize an AIF. This allows for acquiring images with higher spatial resolution and/or SNR, and therefore, increased ability to probe tissue heterogeneity.     

A study to determine whether cavitation occurs around dental ultrasonic scaling instruments

The aim of this investigation was to determine if cavitation occurred around dental ultrasonic scalers and to estimate the amount of cavitation occurring. Three styles of tip (3 x TFI-10, 3 x TFI-3, 3 x TFI-1) were used, in conjunction with a Cavitron SPS ultrasonic generator (Dentsply, USA), to insonate terephthalic acid solution. The hydroxyl radical, [*OH], concentration, produced due to cavitation from the scaler tips, was monitored by fluorescence spectroscopy. Cavitational activity was enhanced at higher power settings and at longer operating times. The tip dimensions and geometry as well as the generator power setting are both important factors that affect the production of cavitation.     

Treatment of trigeminal ganglion neurons in vitro with NGF,GDNF or BDNF: effects on neuronal survival,neurochemical properties and TRPV1-mediated neuropeptide secretion

Background  

Nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) all play important roles in the development of the peripheral sensory nervous system. Additionally, these growth factors are proposed to modulate the properties of the sensory system in the adult under pathological conditions brought about by nerve injury or inflammation. We have examined the effects of NGF, GDNF and BDNF on adult rat trigeminal ganglion (TG) neurons in culture to gain a better understanding of how these growth factors alter the cytochemical and functional phenotype of these neurons, with special attention to properties associated with nociception.     

Growth spiral activity and step velocities on a crystal surface

The normal growth rates and slopes of the dominant growth spirals on a crystal face were measured using a novel application of interferometry and atomic force microscopy. The dislocations responsible for the spirals were also observed directly. In this way it was shown that the velocities of similar steps on growth spirals of different activity, growing simultaneously on the same crystal face, were the same, and hence independent of the growth spirals to which they belonged. With this information the relative activities of the spirals were quantified and discussed in terms of hollow dislocation cores and the back-stress effect.     

Chaotic behavior of a Galerkin model of a two-dimensional flow

Chaotic behavior of a Galerkin model of the Kolmogorov fluid motion equations is demonstrated. The study focuses on the dynamical behavior of limit trajectories branching off secondary periodic solutions. It is shown that four limit trajectories exist and transform simultaneously from periodic solutions to chaotic attractors through a sequence of bifurcations including a periodic-doubling scenario. Some instability regimes display close similarities to those of a discrete dynamical system generated by an interval map.     

Determination of pore space shape and size in porous systems using NMR diffusometry. Beyond the short gradient pulse approximation

The influence of finite length gradient pulses on NMR diffusion experiments on liquids confined to diffuse between two parallel planes is investigated. It is experimentally verified that the pore size decreases when determined using finite gradient pulses if the results are analyzed within the short gradient pulse approximation. The results are analyzed using the matrix formulation. The observed minima in the echo decay profiles are considerably less sharp than theoretical analysis would indicate and we suggest that this is due to the presence of a distribution of pore sizes in the sample. In addition, effects due to the presence of background gradients are discussed. It is argued that effects due to the finite length gradient pulses are relatively minor and in realistic applications the effects due to inhomogeneities in pore sizes and effects due to background gradients will constitute more serious problems in pore size determinations by means of NMR diffusometry.     

Studies on the total synthesis of disorazole C1. An advanced macrocycle intermediate

Synthesis of protected tetradehydro-(6,6'-S)-(14,14'-S)-(16,16'-R)-disorazole (3), a potential precursor to the natural product disorazole C1 (1), is described. Key features of this work include (a) an unprecedented sequential 1,5 O --> O silyl rearrangement/Horner-Wadsworth-Emmons reaction used to construct 18, (b) a highly convergent Sonogashira reaction between the dienyl iodide 7 and the alkyne 8 to assemble the dienyne monomeric fragment 5, and (c) the selective cyclization of 5 to give either the cyclic monomer 23 or the dimer 3.     

Persistence of well-defined collective excitations in a molten transition metal

Well-defined microscopic collective excitations are found in liquid Ni at 1763 K by means of inelastic neutron scattering. Such excitations are supported by the liquid despite an anharmonic character of its thermodynamic functions. Consideration of the detailed shape of the interionic pair potential provides a way to understand why atomic motions at microscopic scales behave in a way much closer to the alkali metals than to the liquefied rare gases.