We report the assessment of cerebral blood flow (CBF) changes with a wide-field laser Doppler imager based on a CCD camera detection scheme, in vivo, in mice. The setup enables the acquisition of data in minimally invasive conditions. In contrast with conventional laser Doppler velocimeters and imagers, the Doppler signature of moving scatterers is measured in the frequency domain, by detuning a heterodyne optical detection. The quadratic mean of the measured frequency shift is used as an indicator of CBF. We observe a significant variability of this indicator in an experiment designed to induce blood flow changes.
The cortical hemodynamic response to somatosensory stimulus is investigated at the level of individual vascular compartments using both depth-resolved optical imaging and in-vivo two-photon microscopy. We utilize a new imaging and spatiotemporal analysis approach that exploits the different characteristic dynamics of responding arteries, arterioles, capillaries and veins to isolate their three-dimensional spatial extent within the cortex. This spatial delineation is validated using vascular casts. Temporal delineation is supported by in-vivo two-photon microscopy of the temporal dynamics and vascular mechanisms of the arteriolar and venous responses. Using these techniques we have been able to characterize the roles of the different vascular compartments in generating and controlling the hemodynamic response to somatosensory stimulus. We find that changes in arteriolar total hemoglobin concentration agree well with arteriolar dilation dynamics, which in turn correspond closely with changes in venous blood flow. For 4-s stimuli, we see only small changes in venous hemoglobin concentration, and do not detect measurable dilation or ballooning in the veins. Instead, we see significant evidence of capillary hyperemia. We compare our findings to historical observations of the composite hemodynamic response from other modalities including functional magnetic resonance imaging. Implications of our results are discussed with respect to mathematical models of cortical hemodynamics, and to current theories on the mechanisms underlying neurovascular coupling. We also conclude that our spatiotemporal analysis approach is capable of isolating and localizing signals from the capillary bed local to neuronal activation, and holds promise for improving the specificity of other hemodynamic imaging modalities.
Controlled precipitation produced aqueous nanoparticle suspensions of a poorly water soluble drug, itraconazole (ITZ), in an amorphous state, despite unusually high potencies (drug weight/ total weight) of up to 94%. Adsorption of the amphiphilic stabilizer hydroxypropylmethylcellulose (HPMC) at the particle-aqueous solution interface arrested particle growth, producing surface areas from 13 to 51 m(2)/g. Dissolution of the particles in acidic media yielded high plateau levels in supersaturation up to 90 times the equilibrium solubility. The degree of supersaturation increased with particle curvature, as characterized by the surface area and described qualitatively by the Kelvin equation. A thermodynamic analysis indicated HPMC maintained amorphous ITZ in the solid phase with a fugacity 90 times the crystalline value, while it did not influence the fugacity of ITZ in the aqueous phase. High surface areas led to more rapid and levels of supersaturation higher than those seen for low-surface area solid dispersions, which undergo crystallization during slow dissolution. The rapid generation of high levels of supersaturation with potent amorphous nanoparticles, containing small amounts of stabilizers oriented at the particle surface, offers new opportunities for improving bioavailability of poorly water soluble drugs.
The Seebeck coefficient, electrical conductivity, and thermal conductivity of individual chromium disilicide nanowires were characterized using a suspended microdevice and correlated with the crystal structure and growth direction obtained by transmission electron microscopy on the same nanowires. The obtained thermoelectric figure of merit of the nanowires was comparable to the bulk values. We show that combined Seebeck coefficient and electrical conductivity measurements provide an effective approach to probing the Fermi Level, carrier concentration and mobility in nanowires.
Rapidly dissolving nanostructured particles containing amorphous repaglinide (REP) were produced by controlled precipitation. Rapid in vitro dissolution rates and high levels of supersaturation (drug concentration/crystalline equilibrium solubility) were achieved using different stabilizing polymers including Hypromellose, polyvinylpyrrolidone, polyvinyl alcohol, and polyethylene glycol. The dissolution and supersaturation characteristics of amorphous REP depended on the surface area of the particles and the miscibility of REP with the polymer employed to prevent drug crystallization in the solid phase. Each of the polymers contained hydrogen bonding groups to favor miscibility with the drug. Of the various formulations investigated, REP/Hypromellose had the highest surface area leading to the highest dissolution rate in aqueous media under sink conditions. For each of the polymers, except for PVA, the level of supersaturation was on the order of 5 and decayed only slightly for up to 24 h. In addition, the amorphous RE P/Hypromellose system produced high supersaturation after 3 months storage at 25 degrees C/60% RH indicating it was stable against crystallization. This understanding of the effect of polymer stabilizers on drug morphology and subsequently, dissolution rates and supersaturation, may be used to facilitate rational design of dosage forms with the potential for improved bioavailability.
J. T. Oden, Diller, K. R., Bajaj, C., Browne, J. C., Hazle, J., Babu�ka, I., Bass, J., Biduat, L., Demkowicz, L., Elliott, A., Feng, Y., Fuentes, D., Prudhomme, S., Rylander, M. N., Stafford, R. J., and Zhang, Y., “Dynamic Data-driven Finite Element Models for Laser Treatment of Cancer,” Numerical Methods For Partial Differential Equations, vol. 23, pp. 904–922, 2007.
The amount, location, and form of NAPL in contaminated vadose zones are controlled by the spatial distribution of water saturation and soil permeability, the NAPL spill scenario, water infiltration events, and vapor transport. To evaluate the effects of these processes, we used the three-phase flow simulator STOMP, which includes a new permeability–liquid saturation–capillary pressure (k–S–P) constitutive model. This new constitutive model considers three NAPL forms: free, residual, and trapped. A 2-D vertical cross-section with five stratigraphic layers was assumed, and simulations were performed for seven cases. The conceptual model of the soil heterogeneity was based upon the stratigraphy at the Hanford carbon tetrachloride (CT) spill site. Some cases considered co-disposal of NAPL with large volumes of wastewater, as also occurred at the Hanford CT site. In these cases, the form and location of NAPL were most strongly influenced by high water discharge rates and NAPL evaporation to the atmosphere. In order to investigate the impact of heterogeneity, the hydraulic conductivity within the lower permeability layer was modeled as a realization of a random field having three different classes. For six extreme cases of 100 realizations, the CT mass that reached the water table varied by a factor of two, and was primarily controlled by the degree of lateral connectivity of the low conductivity class within the lowest permeability layer. The grid size at the top boundary had a dramatic impact on NAPL diffusive flux just after the spill event when the NAPL was present near the ground surface. NAPL evaporation with a fine grid spacing at the top boundary decreased CT mass that reached the water table by 74%, compared to the case with a coarse grid spacing, while barometric pumping had a marginal effect for the case of a continuous NAPL spill scenario considered in this work. For low water infiltration rate scenarios, the distribution of water content prior to a NAPL spill event decreased CT mass that reached the water table by 98% and had a significant impact on the formation of trapped NAPL. For all cases simulated, use of the new constitutive model that allows the formation of residual NAPL increased the amount of NAPL retained in the vadose zone. Density-driven advective gas flow from the ground surface controlled vapor migration in strongly anisotropic layers, causing NAPL mass flux to the lower layer to be reduced. These simulations indicate that consideration of the formation of residual and trapped NAPLs and dynamic boundary conditions (e.g., areas, rates, and periods of different NAPL and water discharge and fluctuations of atmospheric pressure) in the context of full three-phase flow are needed, especially for NAPL spill events at the ground surface. In addition, NAPL evaporation, density-driven gas advection, and NAPL vertical movement enhanced by water flow must be considered in order to predict NAPL distribution and migration in the vadose zone.
Electrophoretic mobilities of TiO2 colloids in an apolar solvent, toluene, were measured by differential-phase optical coherence tomography (DP-OCT). An electrode spacing of 0.18 mm, made possible by optical coherence tomography with transparent electrodes, enables measurement of the electrophoretic mobility with small samples (20 mu L) of highly turbid colloids at low applied electric potential to avoid electrohydrodynamic instability and electrochemical reactions. In the presence of Aerosol-OT reverse micelles, which stabilized the countercharges, the zeta potential was positive for hydrophilic TiO2 (13 mV at 90 mM AOT) and negative for hydrophobic TiO2. The magnitudes of the zeta potentials were very similar for these two types of TiO2 and decreased at the same rate with AOT concentration. For both hydrophilic and hydrophobic TiO2, a general mechanism is presented to describe the zeta potential in terms of preferential partitioning of cations and sulfosuccinate anions between the particle surface and reverse micelle cores in bulk. This preferential partitioning is governed by the hydrophilicities and extents of the particle surfaces and reverse micelle cores, as a function of surfactant and water concentration. The emerging understanding of the complex charging and stabilization mechanisms for colloids in apolar solvents will be highly beneficial for the design of novel materials.