PubMed HealthSearch

Biomedical subjects

J M Pope

Publications and source records attributed to J M Pope.

At least 19 recordsLinked to original sources

The effects of solutes on the freezing properties of and hydration forces in lipid lamellar phases.

Quantitative deuterium nuclear magnetic resonance is used to study the freezing behavior of the water in phosphatidylcholine lamellar phases, and the effect upon it of dimethylsulfoxide (DMSO), sorbitol, sucrose, and trehalose. When sufficient solute is present, an isotropic phase of concentrated aqueous solution may coexist with the lamellar phase at freezing temperatures. We determine the composition of both unfrozen phases as a function of temperature by using the intensity of the calibrated free induction decay signal (FID). The presence of DMSO or sorbitol increases the hydration of the lamellar phase at all freezing temperatures studied, and the size of the increase in hydration is comparable to that expected from their purely osmotic effect. Sucrose and trehalose increase the hydration of the lamellar phase, but, at concentrations of several molal, the increase is less than that which their purely osmotic effect would be expected to produce. A possible explanation is that very high volume fractions of sucrose and trehalose disrupt the water structure and thus reduce the repulsive hydration interaction between membranes. Because of their osmotic effect, all of the solutes studied reduced the intramembrane mechanical stresses produced in lamellar phases by freezing. Sucrose and trehalose at high concentrations produce a greater reduction than do the other solutes.

Biophysical Phenomena

An investigation of the fluidity of concentration polarisation layers in crossflow membrane filtration of an oil-water emulsion using chemical shift selective flow imaging.

A chemical shift selective NMR flow imaging sequence using stimulated echoes for data acquisition is presented. The sequence was tested using a 20% (vol/vol) oil-water emulsion formed from a soluble cutting oil, which was passed through a simple flow phantom to yield two-dimensional velocity distribution maps of the oil droplets and of the water separately. It was then used to investigate the fluidity of concentration polarisation layers formed from the oil droplets during crossflow membrane filtration of a 5% (vol/vol) emulsion of the same cutting oil. A simple membrane filtration module was used for this purpose, with the feedstock emulsion fed into the lumen of a single tubular membrane at a trans-membrane pressure difference P approximately 70 kPa and crossflow Reynolds number, Re, in the range 100-1000. The results confirm a net axial flow rate < 7.5 microns/s (half digital resolution in the velocity dimension) for the oil polarisation layer. Under these conditions, the upper limit for oil flow tangential to the membrane in the polarised layer is less than 15% of the convective flow of oil towards the membrane.

Emulsions

Fast T1 imaging of dual gel samples for diffusion measurements in NMR dosimetry gels.

Diffusion of iron is one of the major problems limiting the usefulness of NMR gel dosimetry. This was studied in dual gel samples using a 4.7T micro-imaging MR scanner and a fast T1 imaging sequence which allowed the acquisition of a 64 x 128 x 8 data sets (phase encoding x frequency encoding x number of inversion times) in less than 15 min. The procedure enabled us to obtain relative relaxation times for any region of interest within the sample. After the two differently doped gels were brought into contact in the dual gel samples (diameter 12 mm), the diffusion could be observed on subsequent images as a function of time. An inverse square root function was used to fit the change of 1/T1 across the junction between the two gel phases. A diffusion constant of 0.014 +/- 0.003 cm2/h was determined for Fe3+ in a typical dosimetry gel (1.5% agarose, 50 mM H2SO4). This could be lowered by adding a chelating agent such as xylenol orange to the gel. It was also found that diffusion was slower in gelatine gels, however these gels tended not to set properly when H2SO4 was added as required for NMR dosimetry. From the present results we propose that a gel consisting of 1.5% agarose (for stability), 3% gelatine and 0.1 mM xylenol orange (to combat diffusion and allow a visual evaluation) is a suitable base for NMR dosimetry gels. The use of a fast T1 imaging sequence reduces acquisition times and therefore the potential impact of diffusion.

Chelating Agents

Limitations of in vitro contact lens dehydration/rehydration data in predicting on-eye dehydration.

PURPOSE: The purpose of this study was to use in vitro dehydration and rehydration data to model the predicted hydration changes that may occur as a soft contact lens loses and gains water on the eye between blinks. METHODS: Using a recent in vitro data set for four lens materials dehydrated and rehydrated in saline, we derived a mathematical model to describe dehydration and rehydration time courses. The model further combined the dehydration and rehydration data iteratively, as a function of blink frequency, and pre-lens break-up time. RESULTS: The model showed that reduced break-up times or decreased blink frequencies significantly affected dehydration rates and steady state dehydration for lenses of a variety of water contents. However, the model did not agree with the commonly accepted clinical belief that high water content lens materials dehydrate more than low water content materials. DISCUSSION: The discrepancy of the model with historical observations may be accounted for by one or more of the following factors, which were not accounted for in the present model: 1) temperature dependent dehydration (as a lens is taken from a room temperature vial and warmed when placed on the eye); 2) the colloid osmotic pressure, ionicity, pH, and chemical potential of tears (compared to saline); and 3) dehydration by other non-evaporative mechanisms.

Blinking

The relaxivity of Gd-EOB-DTPA and Gd-DTPA in liver and kidney of the Wistar rat.

The NMR relaxivities of Gd-EOB-DTPA and Gd-DTPA were determined in the kidney and liver of intact male Wistar rats immediately following sacrifice and in vitro in solutions and gels, at 1.5 T using a clinical MR scanner, T1 and T2 values of tissue samples were derived from spin-echo image sequences. Tissue gadolinium concentrations were determined by radioassay of Gd153, Gd-EOB-DTPA T1 and T2 relaxivities, R1 and R2 (s-1 mmole-1 kg), were found to be 10.7 +/- 0.5 and 22.5 +/- 3.2 respectively, for liver, 2.4 +/- 0.2 and 12.1 +/- 1.7 for kidney cortex, 2.7 +/- 0.2 and 14.5 +/- 1.9 for kidney outer medulla, 2.0 +/- 0.2 and 11.4 +/- 2.1 for kidney inner medulla. Gd-DTPA R1 and R2 were found to be 4.8 +/- 0.4 and 14.5 +/- 3.7 for liver, 1.2 +/- 0.1 and 7.9 +/- 0.8 for kidney cortex, 1.6 +/- 0.1 and 10.2 +/- 1.4 for kidney outer medulla, 1.3 +/- 0.1 and 10.2 +/- 1.2 for kidney inner medulla. Gd-EOB-DTPA and Gd-DTPA R1 was increased in liver compared to agarose gets at 38 degrees C (4.49 +/- 0.03 and 3.47 +/- 0.06), but reduced in kidney tissues. All R2 were elevated compared to agarose gels at 38 degrees C (5.72 +/- 0.12 and 4.12 +/- 0.03). Elevated R2 and R1 (expressed in terms of the concentration of gadolinium per kg of tissue) can be accounted for in part by the lower water content of tissues compared with gels or solutions increased microviscosity and binding to macromolecules. In addition, susceptibility effects may give rise to further increases in R2. By contrast, the reduced R1 observed in kidney may be the result of compartmentalization of the magnetopharmaceuticals. Statistically improved fits were obtained for T1 recovery curves for liver in the presence of Gd-EOB-DTPA when a dual exponential model was used. Assuming in vitro values for the relaxivities of these artificial contrast agents will lead to inaccuracies when relating observed signal enhancement factors to tissue gadolinium concentration.

Animals

The effect of sacrifice on image signal, T1, T2, and T*2 in liver, kidney, and brain of the Wistar rat.

Signal intensity in SE240/25 and GE240/25 images, T*2, T2, and T1 were measured prior to and after sacrifice at 1.5 T in liver, kidney, and brain of Wistar rats. Presacrifice, animals were maintained on 2-3% halothane, ensuring a high saturation of venous haemoglobin with oxygen, which emphasised blood oxygenation level dependent (BOLD) effects upon deoxygenation of haemoglobin postsacrifice. T*2 values (in ms) changed on sacrifice from 27.8 +/- 4.1 to 15.0 +/- 1.1 in liver (p << .001), from 57.4 +/- 6.5 to 52.8 +/- 5.7 in brain (p < .02), and from 52.3 +/- 10.3 to 37.6 +/- 11.9 in kidney cortex (p < .01). T*2 was also reduced in kidney medulla and papilla. T2 reduced on sacrifice (by a lesser amount than T*2), except in brain, which showed a small increase. T1 (ms) changed only in liver, showing a significant increase from 670 +/- 31 to 834 +/- 69 (p << .001). The ratio of signal postsacrifice to presacrifice was lowest in the SE240/25 and GE240/25 images of liver (0.73 +/- 0.03 and 0.52 +/- 0.05, respectively), but increased T1 may account for some of these changes. Expected signal ratios at sacrifice calculated from measured relaxation times agreed well with those observed experimentally. Relaxation changes observed on sacrifice were consistent with deoxygenation of haemoglobin. These results give an estimate of the maximum effects which changes of blood oxygen level might produce at 1.5 T and suggest that contrast due to variation of endogenous deoxyhaemoglobin may be exploitable in the liver.

Animals

Quantitative magnetic resonance flow and diffusion imaging in porous media.

Quantitative flow and diffusion measurements have been made for water in model porous media, using magnetic resonance micro-imaging methods. The samples consisted of compacted glass beads of various sizes down to 1 mm diameter. Typical flow and diffusion images exhibited a spatial resolution of 117 microns x 117 microns and velocities in the range 1-2 mm/s. Comparison of volume flow rates calculated from the flow velocity maps with values measured directly yielded good agreement in all cases. There was also good agreement between the mean diffusion coefficient of water calculated from the diffusion maps and the bulk diffusion coefficient for pure water at the same temperature. In addition, the mean diffusion coefficient did not depend on the pore sizes in the bead diameter range of 1-3 mm. Our results also show that partial volume effects can be compensated by appropriate thresholding of the images prior to the final Fourier transformation in the flow-encoding dimension.

Diffusion

Choice of soft pulse shapes for signal excitation in chemical shift selective imaging.

The choice of soft pulse shapes for chemical shift selective excitation in chemical shift imaging is discussed. In the presence of inhomogeneities in the static magnetic field resulting from susceptibility anomalies, it is important to optimise pulse bandshape and frequency offset as well as bandwidth, in order to minimize artefacts arising from excitation of unwanted resonances. A comparison of the use of Gaussian and sinc shaped excitation pulses in the chemical shift micro-imaging of grapes serves to illustrate some of the effects that may be observed.

Magnetic Resonance Spectroscopy

Hydration forces and membrane stresses: cryobiological implications and a new technique for measurement.

Very large, repulsive forces are measured between various surfaces in water at separations of about a nanometer or less. These forces are important in cryobiology because extracellular freezing usually causes extreme osmotic dehydration of cells. This brings membranes and macromolecules into close approach, and imposes large, anisotropic stresses on them. It is therefore important to study these forces at freezing temperatures. We have studied the freezing and thawing behaviour of lamellar phases of egg yolk lecithin and D2O. Force-hydration and force-separation relations are obtained from the deuterium nuclear magnetic resonance signal as a function of temperature. From these measurements we estimate the magnitude of freezing-induced membrane stresses and discuss their effect on the response of cells and organelles to freezing and thawing.

Cell Membrane

Ni-DTPA doped agarose gel--a phantom material for Gd-DTPA enhancement measurements.

In order to study the relationship between the concentration of Gd-DTPA in tissue, and the resulting changes in relaxation times and signal intensity, a phantom material that has similar relaxation times to tissue and that can be doped with Gd-DTPA is required. The "tissue-equivalent" material should not contain Gd; nor should it alter the relaxivities of Gd-DTPA from their values in aqueous solution (R1 = 4.5 sec-1 mM-1; R2 = 5.5 sec-1 mM-1 at 1.5 T). Conventional materials, based on CuSO4-, MnCl2-, or GdCl3/LaCl3-agarose mixtures, are not suitable, since Gd is displaced from the Gd-DTPA chelate. The new material, consisting of Ni-DTPA dissolved in agarose, is easy to prepare and does not interact with Gd-DTPA. Its relaxation times are stable; relaxivity R1 was within 4% of its aqueous value over 109 days. T1s have low dependence on temperature (0.2-1.0%/degrees C at 21 degrees C) and on field strength, allowing the material to be used as a relaxation time standard for quality assurance. Equations giving the concentration of Ni-DTPA and agarose to produce a required T1 and T2 are provided.

Contrast Media

Flow-selective pulse sequences.

A series of pulse sequences is described which selectively excite signals only from flowing spins. The method is based on the binomial selective excitation sequences employed for solvent suppression in NMR spectroscopy, combined with 180 degrees refocusing of chemical shift and static field inhomogeneity effects and the application of bipolar gradients to distinguish stationary from flowing spins. The effectiveness of the method is demonstrated by experiments on a simple flow phantom.

Humans

Investigation of the tissue equivalence of gels used for NMR dosimetry.

The transition of Fe2+ to Fe3+ in Fricke solution after irradiation results in a change of NMR proton relaxation times in agarose gels which can be used for the dosimetry of ionizing radiation. The main advantage of this system is the possibility of observing dose distributions in 3 dimensions in a medium which is supposed to be tissue equivalent. The aim of the present study was to quantify parameters which determine the tissue equivalence of NMR dosimetry gels. Electron densities and effective atomic numbers were calculated for gels with varying iron, sulphur and agarose concentration. The Hounsfield CT numbers so derived agree well with the CT numbers measured on a clinical CT scanner (effective photon energy 70.7 keV). The Hounsfield CT number of 7.2 +/- 1.5 (n = 9) measured for a 1.5% agarose gel doped with 0.5 mM ammonium ferrous sulphate and 125 mM sulphuric acid compares well with the calculated one of 8 +/- 5. Relaxation times were measured from a series of MR images obtained on a 1.5 T clinical MR scanner. The observed change in 1/T1 of the gel with dose was found to be linear up to 10 Gy (0.084 s-1 Gy-1). No difference in dose response for 10 Gy delivered by four different superficial radiation qualities (HVT = 1.4-7.5 mm Al) could be observed. These findings and the calculated effective atomic number of 7.46 demonstrate the close tissue equivalence of this agarose gel which makes it an ideal tool for the investigation of low energy therapeutic x-rays.

Ferrous Compounds

Motional narrowing of the 2H NMR spectra near the chain melting transition of phospholipid/D2O mixtures.

The reduction in spectral splitting, or motional narrowing, of the deuterium spectra of D2O/phospholipid mixtures near the main chain melting phase transition was studied for palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoylphosphatidylethanolamine (POPE) and equimolar mixtures of the two at 10% hydration. For POPC the splitting was about 1700 Hz in both the fluid and gel phases, dropping to zero near the phase transition (as reported previously). For POPE the splitting remained approximately constant above the phase transition. Below the phase transition the spectrum showed a single broad line whose linewidth varied between 100 Hz and 800 Hz. This was interpreted as being due to small domains of water within a weakly hydrated crystal. POPC:POPE (1:1) samples exhibited motional narrowing behaviour similar to that for POPC except that the splitting above the phase transition was approximately twice that below the transition. The relatively broad temperature range (approximately 20 K) of the transition is explained using a simple physical model involving lipid fluctuations near the phase transition.

Deuterium

Artifacts in chemical shift selective imaging.

The role of susceptibility effects in the production of artifacts in chemical shift images generated by the selective excitation technique is discussed. The effects are demonstrated in images of phantom samples of agarose gels containing small air bubbles. The artifacts can lead to erroneous interpretations, in which the resonances to be resolved exhibit a relatively small chemical shift separation, such as that between water and soluble carbohydrates (sugars).

Artifacts

The application of 3D chemical shift microscopy to noninvasive histochemistry.

Three-dimensional chemical shift imaging methods offer significant advantages over two-dimensional (chemical shift selective) techniques for the study of biological samples which exhibit complex spectra. We have applied 3D-CSI methods to the study of a plant system, (dried fennel mericarps) previously studied by 2D-CSI techniques, obtaining images with in-plane resolution down to 30 microns and special resolution of 0.4 ppm. A modification of the 3D-CSI technique which incorporates water suppression by a combination of pre-saturation and selective excitation is also described and its performance evaluated on both a phantom and a fresh fennel sample.

Ferula

Haemolytic disease of the newborn probably due to anti-ELO, an antibody to a low frequency red cell antigen.

Investigation of mild bilirubinaemia and a positive direct antiglobulin test in a 2 day old baby revealed that the mother's serum contained an antibody against the low frequency antigen ELO, which was present on the father's red cells. Family studies showed that the ELO antigen segregates from Rh, Gc, ADA and PGM1. The ELO antigen is enzyme resistant and therefore not likely to be part of the MNS or Duffy systems. No abnormalities were detected in immunoblotting studies. Although insufficient samples were available to attempt elution of the antibody from the cord cells, it is probable that this case represents the first reported haemolytic disease of the newborn due to anti-ELO.

Adult

Applications of chemical-shift-selective NMR microscopy to the non-invasive histochemistry of plant materials.

Chemical-shift-selective imaging at microscopic resolution has been applied to the study of various plant materials including orange peel, grape berries and both dried and undried fruits of fennel. It is shown that selective imaging of aromatics and carbohydrates as well as water and oil can be performed with in-plane resolution down to 13 microns and slice thicknesses of 1 mm or less, at a field strength of 4.7 Tesla. The noninvasive nature of the method gives it advantages over established methods of plant histochemistry which involve sectioning and staining to reveal different chemical constituents.

Fruit