Timothy Stait-Gardner

Biexponential diffusion decay in formalin‐fixed prostate tissue: Preliminary findings

Magnetic resonance microimaging was used to measure diffusion decay over an extended b‐factor range in a formalin‐fixed normal prostate sample and a Gleason pattern 3+4 cancer tissue sample. The coefficients of biexponential fits to diffusion decay data from 1600 voxels of dimension 160 × 160 × 160 μm3 in each sample were correlated with underlying epithelial and stromal compartment partial volumes estimated from high‐resolution apparent diffusion coefficient (ADC) data (40 × 40 × 40 μm3 voxels) from the same tissue. In the normal tissue sample, the signal fractions of the low and high ADC components of the biexponential fits correlated linearly with partial volumes of epithelial tissue (R2 = 0.6) and stromal tissue (R2 = 0.5), respectively. Similar but weaker correlations were observed in the cancer sample. Epithelium‐containing high spatial resolution voxels appeared to be composed of ∼60% low ADC and ∼40% high ADC component. Stromal voxels appeared to be composed of ∼20% low ADC and ∼80% high ADC component. This preliminary report suggests that distinctly different diffusion properties in microscopically adjacent cell types contribute to the multiexponential diffusion decay phenomenon in prostate tissue. Magn Reson Med, 2012.

Diffusion studies of dihydroxybenzene isomers in water-alcohol systems

Nuclear magnetic resonance diffusion studies can be used to identify different compounds in a mixture. However, because the diffusion coefficient is primarily dependent on the effective hydrodynamic radius, it is particularly difficult to resolve compounds with similar size and structure, such as isomers, on the basis of diffusion. Differential solution interactions between species in certain solutions can afford possibilities for separation. In the present study, the self-diffusion of the three isomers of dihydroxybenzene (i.e., (1,2-) catechol, (1,3-) resorcinol, and (1,4-) hydroquinone) was studied in water, aqueous monohydric alcohols (i.e., ethanol, 1-propanol, tert-butanol), and aqueous ethylene glycol. These systems allowed the effects of isomerism and differential solvent interactions on diffusion to be examined. It was found that, while in aqueous solution these isomers had the same diffusion coefficient, in water-monohydric alcohol systems the diffusion coefficient of catechol differed from those of resorcinol and hydroquinone. The separation was found to increase at higher concentrations of monohydric alcohols. The underlying chemical reasons for these differences were investigated.

Microscopic diffusivity compartmentation in formalin-fixed prostate tissue.

MR microimaging at 16.4 T with 40‐μm isotropic voxels was used to investigate compartmentation of water diffusion in formalin‐fixed prostate tissue. Ten tissue samples (∼ 28 mm3 each) from five organs were imaged. The mean diffusivity of epithelial, stromal, and ductal/acinar compartments was estimated by two methods: ( 1 ) manual region of interest selection and ( 2 ) Gaussian fitting of voxel diffusivity histograms. For the region of interest‐method, the means of the tissue sample compartment diffusivities were significantly different (P < 0.001): 0.54 ± 0.05 μm2/ms for epithelium‐containing voxels, 0.91 ± 0.17 μm2/ms for stroma, and 2.20 ± 0.04 μm2/ms for saline‐filled ducts. The means from the histogram method were also significantly different (P < 0.001): 0.45 ± 0.08 μm2/ms for epithelium‐containing voxels, 0.83 ± 0.16 μm2/ms for stroma, 2.21 ± 0.02 μm2/ms for duct. Estimated partial volumes of epithelial, stromal, and ductal/acinar compartments in a “tissue only” subvolume of each sample were significantly different (P < 0.02) between cancer and normal tissue for all three compartments. It is concluded that the negative correlation between apparent diffusion coefficient and cancer Gleason grade observed in vivo results from an increase of partial volume of epithelial tissue and concomitant decrease of stromal tissue and ductal space. Magn Reson Med, 2012.

Erratum to: Use of diffusion magnetic resonance imaging to correlate the developmental changes in grape berry tissue structure with water diffusion patterns[ Plant Methods (2014); 4(10),35. doi 10.1186/1746-4811-10-35.

[This corrects the article DOI: 10.1186/1746-4811-10-35.].

Numerical analysis of NMR diffusion measurements in the short gradient pulse limit

Pulsed gradient spin-echo (PGSE) NMR diffusion measurements provide a powerful technique for probing porous media. The derivation of analytical mathematical models for analysing such experiments is only straightforward for ideal restricting geometries and rapidly becomes intractable as the geometrical complexity increases. Consequently, in general, numerical methods must be employed. Here, a highly flexible method for calculating the results of PGSE NMR experiments in porous systems in the short gradient pulse limit based on the finite element method is presented. The efficiency and accuracy of the method is verified by comparison with the known solutions to simple pore geometries (parallel planes, a cylindrical pore, and a spherical pore) and also to Monte Carlo simulations. The approach is then applied to modelling the more complicated cases of parallel semipermeable planes and a pore hopping model. Finally, the results of a PGSE measurement on a toroidal pore, a geometry for which there is presently no current analytical solution, are presented. This study shows that this approach has great potential for modelling the results of PGSE experiments on real (3D) porous systems. Importantly, the FEM approach provides far greater accuracy in simulating PGSE diffraction data.

Magnetic Resonance Imaging Detects Placental Hypoxia and Acidosis in Mouse Models of Perturbed Pregnancies

Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T 2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T 2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds.

Laser-generated pair production and Hawking-Unruh radiation

Laser-produced electron-positron pair production has been under discussion in the literature since 1969. Large numbers of positrons have been generated by lasers for a few years in studies which are also related to the studies of the physics of the fast ignitor laser fusion concept. For electron-positron pair production in vacuum due to vacuum polarization as predicted by Heisenberg (1934) with electrostatic fields, high-frequency laser fields with intensities around 10 28 W/cm 2 are necessary and may be available within a number of years. A similar electron acceleration by gravitation near black holes denoted as Hawking-Unruh radiation was discussed in 1985 by McDonald. The conditions are considered in view of the earlier work on pair production, change of statistics for electrons in relativistic black body radiation, and an Einstein recoil mechanism with a consequence of a physical foundation of the fine structure constant.

Use of diffusion magnetic resonance imaging to correlate the developmental changes in grape berry tissue structure with water diffusion patterns.

BackgroundOver the course of grape berry development, the tissues of the berry undergo numerous morphological transformations in response to processes such as water and solute accumulation and cell division, growth and senescence. These transformations are expected to produce changes to the diffusion of water through these tissues detectable using diffusion magnetic resonance imaging (MRI). To assess this non-invasive technique diffusion was examined over the course of grape berry development, and in plant tissues with contrasting oil content.ResultsIn this study, the fruit of Vitis vinfera L. cv. Semillon at seven different stages of berry development, from four weeks post-anthesis to over-ripe, were imaged using diffusion tensor and transverse relaxation MRI acquisition protocols. Variations in diffusive motion between these stages of development were then linked to known events in the morphological development of the grape berry. Within the inner mesocarp of the berry, preferential directions of diffusion became increasingly apparent as immature berries increased in size and then declined as berries progressed through the ripening and senescence phases. Transverse relaxation images showed radial striation patterns throughout the sub-tissue, initiating at the septum and vascular systems located at the centre of the berry, and terminating at the boundary between the inner and outer mesocarp. This study confirms that these radial patterns are due to bands of cells of alternating width that extend across the inner mesocarp. Preferential directions of diffusion were also noted in young grape seed nucelli prior to their dehydration. These observations point towards a strong association between patterns of diffusion within grape berries and the underlying tissue structures across berry development. A diffusion tensor image of a post-harvest olive demonstrated that the technique is applicable to tissues with high oil content.ConclusionThis study demonstrates that diffusion MRI is a powerful and information rich technique for probing the internal microstructure of plant tissues. It was shown that macroscopic diffusion anisotropy patterns correlate with the microstructure of the major pericarp tissues of cv. Semillon grape berries, and that changes in grape berry tissue structure during berry development can be observed.

Macromolecular Crowding Studies of Amino Acids Using NMR Diffusion Measurements and Molecular Dynamics Simulations

Molecular crowding occurs when the total concentration of macromolecular species in a solution is so high that a considerable proportion of the volume is physically occupied and therefore not accessible to other molecules. This results in significant changes in the solution properties of the molecules in such systems. Macromolecular crowding is ubiquitous in biological systems due to the generally high intracellular protein concentrations. The major hindrance to understanding crowding is the lack of direct comparison of experimental data with theoretical or simulated data. Self-diffusion is sensitive to changes in the molecular weight and shape of the diffusing species, and the available diffusion space (i.e., diffusive obstruction). Consequently, diffusion measurements are a direct means for probing crowded systems including the self-association of molecules. In this work, nuclear magnetic resonance measurements of the self-diffusion of four amino acids (glycine, alanine, valine and phenylalanine) up to their solubility limit in water were compared directly with molecular dynamics simulations. The experimental data were then analyzed using various models of aggregation and obstruction. Both experimental and simulated data revealed that the diffusion of both water and the amino acids were sensitive to the amino acid concentration. The direct comparison of the simulated and experimental data afforded greater insights into the aggregation and obstruction properties of each amino acid.

Difference between Hawking and Unruh radiation derived from studies about pair production by lasers in vacuum

Laser acceleration of electrons in laser fields of intensities above 10 28 W/cm 2 were found to be in the same range as acceleration at the surface of black holes, where the laser intensities are in the range of pair production in vacuum due to vacuum polarization. The results in connection with the black holes arrived at similarities to the Hawking and Unruh radiation. We present here results based on the thermodynamics of the vacuum fluctuations that there is a difference between Hawking and Unruh effects in connection with the Casimir effect in view of the vacuum properties for laser produced pairs in a vacuum.