Magnetic Resonance Imaging Biomarkers of Renal Structure and Function

The kidney's major role in filtration depends on its high blood flow, concentrating mechanisms, and biochemical activation. The kidney's greatest strengths also lead to vulnerability for drug-induced nephrotoxicity and other renal injuries. The current standard to diagnose renal injuries is with a percutaneous renal biopsy, which can be biased and insufficient. In one particular case, biopsy of a kidney with renal cell carcinoma can actually initiate metastasis. Tools that are sensitive and specific to detect renal disease early are essential, especially noninvasive diagnostic imaging. While other imaging modalities (ultrasound and x-ray/CT) have their unique advantages and disadvantages, MRI has superb soft tissue contrast without ionizing radiation. More importantly, there is a richness of contrast mechanisms in MRI that has yet to be explored and applied to study renal disease.

The focus of this work is to advance preclinical imaging tools to study the structure and function of the renal system. Studies were conducted in normal and disease models to understand general renal physiology as well as pathophysiology. This dissertation is separated into two parts--the first is the identification of renal architecture with ex vivo MRI; the second is the characterization of renal dynamics and function with in vivo MRI. High resolution ex vivo imaging provided several opportunities including: 1) identification of fine renal structures, 2) implementation of different contrast mechanisms with several pulse sequences and reconstruction methods, 3) development of image-processing tools to extract regions and structures, and 4) understanding of the nephron structures that create MR contrast and that are important for renal physiology. The ex vivo studies allowed for understanding and translation to in vivo studies. While the structure of this dissertation is organized by individual projects, the goal is singular: to develop magnetic resonance imaging biomarkers for renal system.

The work presented here includes three ex vivo studies and two in vivo studies:

1) Magnetic resonance histology of age-related nephropathy in sprague dawley.

2) Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice.

3) Susceptibility tensor imaging of the kidney and its microstructural underpinnings.

4) 4D MRI of renal function in the developing mouse.

5) 4D MRI of polycystic kidneys in rapamycin treated Glis3-deficient mice.

Stability of Sr adatom model structures for SrTiO3(001) surface reconstructions

We report results of first-principles calculations on the thermodynamic stability of different Sr adatom structures that have been proposed to explain some of the observed reconstructions of the (001) surface of strontium titanate (Kubo and Nozoye 2003 Surf Sci. 542 177). From surface free energy calculations, a phase diagram is constructed indicating the range of conditions over which each structure is most stable. These results are compared with Kubo and Nozoye's experimental observations. It is concluded that low Sr adatom coverage structures can only be explained if the surface is far from equilibrium. Intermediate coverage structures are stable only if the surface is in or very nearly in equilibrium with the strontium oxide.

Magnetic and electrode structure design for a new EBIT

Electron beam trajectory simulations have been performed to design a new electron beam ion trap. The design of the magnet and electrode structures was optimized based on the results of the simulations. (C) 2003 Elsevier Science B.V. All rights reserved.

Current-driven magnetic rearrangements in spin-polarized point contacts

A method for investigating the dynamics of atomic magnetic moments in current-carrying magnetic point contacts under bias is presented. This combines the nonequilibrium Green's function (NEGF) method for evaluating the current and the charge density with a description of the dynamics of the magnetization in terms of quasistatic thermally activated transitions between stationary configurations. This method is then implemented in a tight-binding (TB) model with parameters chosen to simulate the main features of the electronic structures of magnetic transition metals. We investigate the domain wall (DW) migration in magnetic monoatomic chains sandwiched between magnetic leads, and for realistic parameters find that collinear arrangement of the magnetic moments of the chain is always favorable. Several stationary magnetic configurations are identified, corresponding to a different number of Bloch walls in the chain and to a different current. The relative stability of these configurations depends on the geometrical details of the junction and on the bias; however, we predict transitions between different configurations with activation barriers of the order of a few tens of meV. Since different magnetic configurations are associated with different resistances, this suggests an intrinsic random telegraph noise at microwave frequencies in the I-V curves of magnetic atomic point contacts at room temperature. Finally, we investigate whether or not current-induced torques are conservative.

Self-focusing and envelope pulse generation in nonlinear magnetic metamaterials

The self-modulation of waves propagating in nonlinear magnetic metamaterials is investigated. Considering the propagation of a modulated amplitude magnetic field in such a medium, we show that the self-modulation of the carrier wave leads to a spontaneous energy localization via the generation of localized envelope structures (envelope solitons), whose form and properties are discussed. These results are also supported by numerical calculations.

Surface plasmons in layered structures with semiconductor and metallic films

The complete spectrum of eigenwaves including surface plasmon polaritons (SPP), dynamic (bulk) and complex waves in the layered structures containing semiconductor and metallic films has been explored. The effects of loss, geometry and the parameters of dielectric layers on the eigenmode spectrum and, particularly, on the SPP modes have been analysed using both the asymptotic and rigorous numerical solutions of the full-wave dispersion equation. The field and Poynting vector distributions have been examined to identify the modes and elucidate their properties. It has been shown that losses and dispersion of permittivity qualitatively alter the spectral content and the eigenwave properties. The SPP counter-directional power fluxes in the film and surrounding dielectrics have been attributed to vortices of power flow, which are responsible for the distinctive features of SPP modes. It has been demonstrated for the first time that the maximal attainable slow-wave factor of the SPP modes guided by thin Au films at optical frequencies is capped not by losses but the frequency dispersion of the actual Au permittivity. © 2009 EDP Sciences.

A study of magnetic bright points in the Na I D1 line.

High-cadence, multiwavelength, optical observations of solar magnetic bright points (MBPs), captured at the disk center using the ROSA and IBIS imaging systems on the Dunn Solar Telescope, are presented. MBPs manifesting in the Na I D-1 core are found to preferentially exist in regions containing strong downflows, in addition to cospatial underlying photospheric magnetic field concentrations. Downdrafts within Na I D-1 bright points exhibit speeds of up to 7 km s(-1), with preferred structural symmetry in intensity, magnetic field, and velocity profiles about the bright point center. Excess intensities associated with G-band and Ca II K observations of MBPs reveal a power-law trend when plotted as a function of the magnetic flux density. However, Na I D-1 observations of the same magnetic features indicate an intensity plateau at weak magnetic field strengths below approximate to 150 G, suggesting the presence of a two-component heating process: one which is primarily acoustic and the other predominantly magnetic. We suggest that this finding is related to the physical expansion of magnetic flux tubes, with weak field strengths (approximate to 50 G) expanding by similar to 76%, compared to a similar to 44% expansion when higher field strengths (approximate to 150 G) are present. These observations provide the first experimental evidence of rapid downdrafts in Na I D-1 MBPs and reveal the nature of a previously unresolved intensity plateau associated with these structures.

Barrier height variations and interface properties of PtSi/Si structures

To study some of the interfacial properties of PtSi/Si diodes, Schottky structures were fabricated on (100) crystalline silicon substrates by conventional thermal evaporation of Pt on Si followed by annealing at different temperatures (from 400 degrees C to 700 degrees C) to form PtSi. The PtSi/n-Si diodes, all yielded Schottky barrier (SB) heights that are remarkably temperature dependent. The temperature range (20-290 K) over which the I-V characteristics were measured in the present study is broader with a much lower limit (20 K), than what is usually reported in literature. These variations in the barrier height are adequately interpreted by introducing spatial inhomogeneity into the barrier potential with a Gaussian distribution having a mean barrier of 0.76 eV and a standard deviation of 30 meV. Multi-frequency capacitance-voltage measurements suggest that the barrier is primarily controlled by the properties of the silicide-silicon interface. The forward C-V characteristics, in particular, show small peaks at low frequencies that can be ascribed to interface states rather than to a series resistance effect.

The Area Distribution of Solar Magnetic Bright Points

Magnetic bright points (MBPs) are among the smallest observable objects on the solar photosphere. A combination of G-band observations and numerical simulations is used to determine their area distribution. An automatic detection algorithm, employing one-dimensional intensity profiling, is utilized to identify these structures in the observed and simulated data sets. Both distributions peak at an area of approximate to 45,000 km(2), with a sharp decrease toward smaller areas. The distributions conform with log-normal statistics, which suggests that flux fragmentation dominates over flux convergence. Radiative magneto-convection simulations indicate an independence in the MBP area distribution for differing magnetic flux densities. The most commonly occurring bright point size corresponds to the typical width of inter-granular lanes.

Weakly nonlinear vertical dust grain oscillations in dusty plasma crystals in the presence of a magnetic field

The weakly nonlinear regime of transverse paramagnetic dust grain oscillations in dusty (complex) plasma crystals is discussed. The nonlinearity, which is related to the sheath electric/magnetic field(s) and to the intergrain (electrostatic/magnetic dipole) interactions, is shown to lead to the generation of phase harmonics and, in the case of propagating transverse dust-lattice modes, to the modulational instability of the carrier wave due to self-interaction. The stability profile depends explicitly on the form of the electric and magnetic fields in the plasma sheath. The long term evolution of the modulated wave packet, which is described by a nonlinear Schrodinger-type equation, may lead to propagating localized envelope structures whose exact forms are presented and discussed. Explicit suggestions for experimental investigations are put forward. (C) 2004 American Institute of Physics.

An introduction to biological nuclear magnetic resonance spectroscopy

ABSTRACT Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful analytical techniques available to biology. This review is an introduction to the potential of this method and is aimed at readers who have little or no experience in acquiring or analyzing NMR spectra. We focus on spectroscopic applications of the magnetic resonance effect, rather than imaging ones, and explain how various aspects of the NMR phenomenon make it a versatile tool with which to address a number of biological problems. Using detailed examples, we discuss the use of 1H NMR spectroscopy in mixture analysis and metabolomics, the use of 13C NMR spectroscopy in tracking isotopomers and determining the flux through metabolic pathways (‘fluxomics’) and the use of 31P NMR spectroscopy in monitoring ATP generation and intracellular pH homeotasis in vivo. Further examples demonstrate how NMR spectroscopy can be used to probe the physical environment of a cell by measuring diffusion and the tumbling rates of individual metabolites and how it can determine macromolecular structures by measuring the bonds and distances which separate individual atoms. We finish by outlining some of the key challenges which remain in NMR spectroscopy and we highlight how recent advances— such as increased magnet field strengths, cryogenic cooling, microprobes and hyperpolarisation—are opening new avenues for today’s biological NMR spectroscopists.

The velocity distribution of solar photospheric magnetic bright points.

We use high spatial resolution observations and numerical simulations to study the velocity distribution of solar photospheric magnetic bright points. The observations were obtained with the Rapid Oscillations in the Solar Atmosphere instrument at the Dunn Solar Telescope, while the numerical simulations were undertaken with the MURaM code for average magnetic fields of 200 G and 400 G. We implemented an automated bright point detection and tracking algorithm on the data set and studied the subsequent velocity characteristics of over 6000 structures, finding an average velocity of approximately 1 km s(-1), with maximum values of 7 km s(-1). Furthermore, merging magnetic bright points were found to have considerably higher velocities, and significantly longer lifetimes, than isolated structures. By implementing a new and novel technique, we were able to estimate the background magnetic flux of our observational data, which is consistent with a field strength of 400 G.

Generation of scaled protogalactic seed magnetic fields in laser-produced shock waves

The standard model for the origin of galactic magnetic fields is through the amplification of seed fields via dynamo or turbulent processes to the level consistent with present observations. Although other mechanisms may also operate, currents from misaligned pressure and temperature gradients (the Biermann battery process) inevitably accompany the formation of galaxies in the absence of a primordial field. Driven by geometrical asymmetries in shocks associated with the collapse of protogalactic structures, the Biermann battery is believed to generate tiny seed fields to a level of about 10 gauss (refs 7, 8). With the advent of high-power laser systems in the past two decades, a new area of research has opened in which, using simple scaling relations, astrophysical environments can effectively be reproduced in the laboratory. Here we report the results of an experiment that produced seed magnetic fields by the Biermann battery effect. We show that these results can be scaled to the intergalactic medium, where turbulence, acting on timescales of around 700 million years, can amplify the seed fields sufficiently to affect galaxy evolution.

Self-Similar Nested Flux Closure Structures in a Tetragonal Ferroelectric

In specific solid-state materials, under the right conditions, collections of magnetic dipoles are known to spontaneously form into a variety of rather complex geometrical patterns, exemplified by vortex and skyrmion structures. While theoretically, similar patterns should be expected to form from electrical dipoles, they have not been clearly observed to date: the need for continued experimental exploration is therefore clear. In this Letter we report the discovery of a rather complex domain arrangement that has spontaneously formed along the edges of a thin single crystal ferroelectric sheet, due to surface-related depolarizing fields. Polarization patterns are such that nanoscale “flux-closure” loops are nested within a larger mesoscale flux closure object. Despite the orders of magnitude differences in size, the geometric forms of the dual-scale flux closure entities are rather similar.