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PurposeThe purpose of this study was to improve triggering efficiency of the prospective respiratory amplitude-triggered 4-dimensional magnetic resonance imaging (4DMRI) method and to develop a 4DMRI imaging protocol that could offer T2 weighting for better tumor visualization, good spatial coverage and spatial resolution, and respiratory motion sampling within a reasonable amount of time for radiation therapy applications.Methods and materialsThe respiratory state splitting (RSS) and multi-shot acquisition (MSA) methods were analytically compared and validated in a simulation study by using the respiratory signals from 10 healthy human subjects. The RSS method was more effective in improving triggering efficiency. It was implemented in prospective respiratory amplitude-triggered 4DMRI. 4DMRI image datasets were acquired from 5 healthy human subjects. Liver motion was estimated using the acquired 4DMRI image datasets.ResultsThe simulation study showed the RSS method was more effective for improving triggering efficiency than the MSA method. The average reductions in 4DMRI acquisition times were 36% and 10% for the RSS and MSA methods, respectively. The human subject study showed that T2-weighted 4DMRI with 10 respiratory states, 60 slices at a spatial resolution of 1.5 × 1.5 × 3.0 mm(3) could be acquired in 9 to 18 minutes, depending on the individual's breath pattern. Based on the acquired 4DMRI image datasets, the ranges of peak-to-peak liver displacements among 5 human subjects were 9.0 to 12.9 mm, 2.5 to 3.9 mm, and 0.5 to 2.3 mm in superior-inferior, anterior-posterior, and left-right directions, respectively.ConclusionsWe demonstrated that with the RSS method, it was feasible to acquire high-quality T2-weighted 4DMRI within a reasonable amount of time for radiation therapy applications.

We previously established that probucol decreases basal expression of VCAM-1 in the aorta of WHHL rabbits and inhibits the up-regulation of VCAM-1 expression that normally accompanies atherogenesis. To determine whether this effect is shared by other antioxidants in vivo, we now investigated whether a structurally unrelated antioxidant, vitamin E, also inhibits arterial VCAM-1 expression and whether the degree of VCAM-1 inhibition correlates with the reduction of atherosclerosis or the antioxidant protection of LDL. Atherogenesis and VCAM-1 mRNA and protein were determined in four groups of NZW rabbits (n = 6;-8) fed 0.5% cholesterol alone or supplemented with 0.1% vitamin E, a low dose (0.04;-0.075%) of probucol yielding the same degree of antioxidant protection of plasma LDL as vitamin E, or a high dose (0.5%) of probucol, and in normocholesterolemic rabbits. After 81 days, extensive atherosclerosis and a greater than 4-fold up-regulation of VCAM-1 mRNA was seen in rabbits on high cholesterol diet, mostly in the intima. Treatment with vitamin E, high-dose probucol, and low-dose probucol significantly decreased VCAM-1 mRNA by 49.0, 74.9, and 57. 5%, respectively, and reduced atherosclerosis in adjacent segments of the thoracic aorta to a similar degree as reported by previous studies. Immunocytochemistry confirmed that lesions of antioxidant-treated animals also contained less VCAM-1 protein. Neither the degree of VCAM-1 inhibition nor the extent of atherosclerosis correlated with the degree of antioxidant protection of plasma LDL.In summary, treatment with structurally unrelated antioxidants conveyed different degrees of antioxidant protection to plasma LDL but significantly reduced VCAM-1 expression in vivo and inhibited atherogenesis. This is consistent with the assumption that antiatherogenic effects of antioxidants may in part be mediated by interference with oxidation-dependent intracellular signaling.

To identify factors regulating neurogenesis and neuronal death in mammals and to determine the mechanisms by which these factors act, we have studied mouse olfactory epithelium using two different experimental paradigms: tissue culture of olfactory epithelium purified from mouse embryos; and ablation of the olfactory bulb in adult mice, a procedure that induces olfactory receptor neuron (ORN) death and neurogenesis in vivo. Studies of olfactory epithelium cultures have allowed us to characterize the cellular stages in olfactory neurogenesis and to identify factors regulating proliferation and differentiation of precursor cells in the ORN lineage. Studies of adult olfactory epithelium have enabled us to determine that all cell types in this lineage-proliferating neuronal precursors, immature ORNs and mature ORNs-undergo cell death following olfactory bulb ablation and that this death has characteristics of programmed cell death or apoptosis. In vitro studies have confirmed that neuronal cells of the olfactory epithelium undergo apoptotic death and have permitted identification of several polypeptide growth factors that promote survival of a fraction of ORNs. Using this information, we have begun to explore whether these factors, as well as genes known to play crucial roles in cell death in other systems, function to regulate apoptosis and neuronal regeneration in the adult olfactory epithelium following lesion-induced ORN death.

The hyperpolarizabilities γ of CH4, CF4, and SF6 were measured by the dc Kerr effect at wavelengths from 457.9 to 1092 nm. Vibrational hyperpolarizabilities γv were obtained by combining these measurements with electric-field-induced second harmonic generation (ESHG) measurements. The vibrational contribution to the hyperpolarizability ranges from 6% to 35% of the total. At high optical frequency the difference between γv for Kerr and γv for ESHG is approximately constant, and has values 18, 31, and 51×10-63 C4 m4 J-3 for CH4, CF4, and SF6, respectively. The experimental results are in good quantitative agreement with the results of recent ab initio calculations of the frequency dependence of γv for CH4, except for a small but non-negligible discrepancy at high frequency. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The Raman spectra of the vibrational fundamental, first overtone and second overtone transitions of the H2 molecule were recorded using visible and ultraviolet argon–ion laser excitation. The ratios of transition polarizability matrix elements, α01,21/α01,11 and α01,31/α01,11, were determined from the measured intensities of the Q(1) Raman lines v,J=0,1→v’,1 for v’=1,2,3. The experimentally determined value of the Raman first overtone matrix element is in good agreement with the value from the best ab initio calculation. [ABSTRACT FROM AUTHOR]

Expressions are derived for the vibrational second hyperpolarizability γv of SF6, in the static limit and for the nonlinear-optical processes of the dc Kerr effect, electric-field-induced second harmonic generation (ESHG), and third harmonic generation (THG). These expressions give γv in terms of vibrational transition dipole, polarizability, and first hyperpolarizability matrix elements (μ,α,β). The matrix elements needed in the numerical evaluation of γv are obtained from the literature and from the Raman scattering measurements reported here. In the static limit it is found that γvapprox. 20 γe, where γe is the electronic contribution to γ. At optical frequencies γv is still comparable to γe in magnitude, and it shows significant frequency dependence. [ABSTRACT FROM AUTHOR]

The frequency dependence of the second hyperpolarizability (γ) of CF4 has been measured in the visible (488 nm<λ<660 nm) by means of gas-phase electric-field-induced second harmonic generation (ESHG). The results of these experiments are compared with the results of other nonlinear optics experiments which have measured γ by third harmonic generation (THG), ESHG, and the dc Kerr effect. In order to make this comparison, expressions for the vibrational contributions to γCF4 have been derived and numerically evaluated for each of these optical processes. This comparison indicates that vibrational contributions to γCF4 are significant for both the dc Kerr effect and ESHG. [ABSTRACT FROM AUTHOR]

The frequency dependence of the second hyperpolarizability (γ) of CO2 has been measured in the visible (488<λ<693 nm) by means of gas phase electric-field-induced second-harmonic generation (ESHG). Comparison of these results with the results for several other third-order nonlinear optical processes suggests that there are significant vibrational contributions to γCO2. [ABSTRACT FROM AUTHOR]

The frequency dependence of the second hyperpolarizabilities (γ ) of Kr and Xe have been measured in the visible by means of gas phase electric-field-induced second-harmonic generation (ESHG). A simple model relating the dispersion of the nonresonant electronic contribution to γ for different third-order nonlinear optical processes is derived. This model is tested by comparing the results obtained here with those obtained by other methods. [ABSTRACT FROM AUTHOR]

The nonlinear susceptibility of acetonitrile has been measured in both the gas and liquid phases by dc electric field-induced second harmonic generation (dc-SHG or EFISH). The EFISH signal for this molecule is dominated by the first hyperpolarizability β. It is shown that local field factors do not adequately describe the effect of the solvent environment. Thus it is not possible to extract ‘‘gas phase’’ values of hyperpolarizabilities from measurements made in solution. First and second hyperpolarizabilities, β and γ, have been calculated for acetonitrile using ab initio techniques. These calculations are compared to the gas phase experimental measurements. Excellent agreement is obtained when electron correlation effects are included. [ABSTRACT FROM AUTHOR]

Evaluation of microbial water quality is commonly based on monitoring populations of fecal indicator organisms (FIO) such as Escherichia coli (EC) and enterococci (ENT). The occurrence of elevated FIO concentrations in surface waters after storm events is well documented and has been attributed to runoff and sediment resuspension. The reasons for FIO concentration variation under baseflow conditions are less clear. The objective of this study was to quantify the variability of EC and ENT in two small streams running through agricultural land use areas. FIO concentrations were measured at upstream and downstream locations under baseflow conditions. Concentrations were not significantly different along cross-sections of the streams. Diurnal concentration trends were observed at each of the sampling locations. Significant differences in concentrations between upstream and downstream locations were noted for both creeks during baseflow periods when no runoff or sediment resuspension occurred. A hypothetical explanation is that indicator organisms are released from sediments during baseflow conditions due to the effect of groundwater influx into streams or due to the motility of indicator organisms. If confirmed, this hypothesis may affect our understanding of the role of sediments in the microbial quality of surface waters. [ABSTRACT FROM AUTHOR]

A high r1 relaxivity manganese–gadolinium nanocolloid (α v β 3 -MnOL-Gd NC) was developed and effectively detected atherosclerotic angiogenesis in rabbits fed cholesterol-rich diets for 12 months using a clinical MRI scanner (3 T). 3D mapping of neovasculature signal intensity revealed the spatial coherence and intensity of plaque angiogenic expansion, which may, with other high risk MR bioindicators, help identify high-risk patients with moderate (40% to 60%) vascular stenosis. Microscopy confirmed the predominant media and plaque distribution of fluorescent α v β 3 -MnOL-Gd NC, mirroring the MR data. An expected close spatial association of α v β 3 -integrin neovasculature and macrophages was noted, particularly within plaque shoulder regions. Manganese oleate bioelimination occurred via the biliary system into feces. Gd-DOTA was eliminated through the bile–fecal and renal excretion routes. α v β 3 -MnOL-Gd NC offers an effective vehicle for T1w neovascular imaging in atherosclerosis. From the Clinical Editor Cerebrovascular accidents are a leading cause of mortality and morbidity worldwide. The acute formation of thrombus following atherosclerotic plaque rupture has been well recognized as the etiology of stroke. The authors studied microanatomical features of vulnerable atherosclerotic plaque in this article, in an attempt to identify those with high risk of rupture. Gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) was developed as a novel contrast agent for MRI. They show that this agent is effective in providing neovascular imaging. [ABSTRACT FROM AUTHOR]

High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium–manganese hybrid nanocolloid (MnOL-Gd NC; 138 ± 10 (D av )/nm; PDI: 0.06; zeta: − 27 ± 2 mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5 nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10 nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk. From the Clinical Editor The authors developed a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) in this study. These were used as a high-relaxivity paramagnetic MR molecular imaging agent in experimental models. It was shown that MnOL-Gd NC could provide high T1w MR contrast for targeted imaging. As the level of gadolinium used was reduced, there was also reduced risk of systemic side effects from complement activation. [ABSTRACT FROM AUTHOR]

Due to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents have been widely used to test the safety and efficacy for pharmaceutical development in human disease. In this report, MR cholangiography demonstrated an unexpected rapid (< 5 min) biliary elimination of gadolinium–perfluorocarbon nanoparticles (approximately 250 nm diameter) into the common bile duct and small intestine of rats, which is notably different from nanoparticle clearance patterns in larger animals and humans. Unawareness of this dissimilarity in nanoparticle clearance mechanisms between small animals and humans may lead to fundamental errors in predicting nanoparticle efficacy, pharmacokinetics, biodistribution, bioelimination, and toxicity. From the Clinical Editor Comprehensive understanding of nanoparticle clearance is a clear prerequisite for human applications of nanomedicine-based therapeutic approaches. Through a novel use of MR cholangiography, this study demonstrates unusually rapid hepatic clearance of gadolinium-perfluorocarbon nanoparticles in rodents, in a pattern that is different than what is observed in larger animals and humans, raising awareness of important differences between common rodent-based models and larger mammals. [ABSTRACT FROM AUTHOR]

Modeling inactivation of indicator microorganisms is a necessary component of microbial water quality forecast and management recommendations. The linear semi-logarithmic (LSL) model is commonly used to simulate the dependencies of bacterial concentrations in waters on time. There were indications that assumption of the semi-logarithmic linearity may not be accurate enough in waters. The objective of this work was to compare performance of the LSL and the two-parametric Weibull inactivation models with data on survival of indicator organism Escherichia coli in various types of water from a representative database of 167 laboratory experiments. The Weibull model was preferred in >99% of all cases when the root mean squared errors and Nash-Sutcliffe statistics were compared. Comparison of corrected Akaike statistic values gave the preference to the Weibull model in only 35% of cases. This was caused by (i) a small number of experimental points on some inactivation curves, (ii) closeness of the shape parameter of the Weibull equation to one, and (iii) piecewise log-linear inactivation dynamic that could be well described by neither of the two models compared. Based on the Akaike test, the Weibull model was favored in agricultural, lake, and pristine waters, whereas the LSL model was preferred for groundwater, wastewater, rivers, and marine waters. The decimal reduction time parameter of both the LSL and Weibull models exhibited an Arrhenius-type dependence on temperature. Overall, the existing E. coli inactivation data indicate that the application of the Weibull model can improve the predictive capabilities of microbial water quality modeling. [ABSTRACT FROM AUTHOR]

Beef feedlot manure distributed to row crop production areas is a potential surface water contaminant source of the steroid hormones commonly used in beef cattle production. This article reports on research conducted at the University of Nebraska Haskell Agricultural Laboratory near Concord, Nebraska, in July 2009. Manure, collected from beef feedlot pens, was stockpiled for ten months prior to application to a row crop field. Previous research identified that the detection frequency of steroid hormones in beef manure varies greatly. Thus, a surrogate (17cr-ethynylestradiol, EE2) was applied at a rate of 75 g ha-1 to ensure detectable concentrations in surface runoff samples. EE2 was applied directly to beef cattle manure and to bare soil. The EE2 and manure were either incorporated using a single disk treatment (T) or left on the soil surface in a no-till practice (NT). .4 rainfall simulation experiment was conducted 24 h after manure and EE2 incorporation using a factorial design consisting of tillage, manure, and EE2 treatments. Runoff samples were collected at 5 min intervals during a 30 min runoff period for each plot. Results indicated 96% less EE2 mass transport from disk-tilled plots compared to no-till. The greatest loss of EE2 was 156 and 6 mg ha-1 from no-till and disked plots, respectively. Results of this study showed that a single-pass disk tillage treatment can limit the overland transport of steroid hormones from crop production areas. [ABSTRACT FROM AUTHOR]