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MMP-2 expression during early avian cardiac and neural crest morphogenesis.

Matrix metalloproteinase-type 2 (MMP-2) degrades extracellular matrix, mediates cell migration and tissue remodeling, and is implicated in mediating neural crest (NC) and cardiac development. However, there is little information regarding the expression and distribution of MMP-2 during cardiogenesis and NC morphogenesis. To elucidate the role of MMP-2, we performed a comprehensive study on the temporal and spatial distribution of MMP-2 mRNA and protein during critical stages of early avian NC and cardiac development. We found that ectodermally derived NC cells did not express MMP-2 mRNA during their initial formation and early emigration but encountered MMP-2 protein in basement membranes deposited by mesodermal cells. While NC cells did not synthesize MMP-2 mRNA early in migration, MMP-2 expression was seen in NC cells within the cranial paraxial and pharyngeal arch mesenchyme at later stages but was never detected in NC-derived neural structures. This suggested NC MMP-2 expression was temporally and spatially dependent on tissue interactions or differed within the various NC subpopulations. MMP-2 was first expressed within cardiogenic splanchnic mesoderm before and during the formation of the early heart tube, at sites of active pharyngeal arch and cardiac remodeling, and during cardiac cushion cell migration. Collectively, these results support the postulate that MMP-2 has an important functional role in early cardiogenesis, NC cell and cardiac cushion migration, and remodeling of the pharyngeal arches and cardiac heart tube.

Animals↗

In search of spatial extremes.

In environmental studies attention increasingly focuses on identification of spatial extremes: locations with observations that are apparently higher than either a preset background threshold or neighbouring observations. We consider various procedures for identifying values and locations of these extremes: extreme value theory, conditionally simulated fields and disjunctive kriging. In a recent research project we studied the distribution of nine environmental pollutants (heavy metals, polyaromatic hydrocarbons and mineral oil) in a large industrial estate in the southern Netherlands. This area is interesting as it is influenced by three contaminating processes: inundation by the river Meuse, anthropogenic heightening with contaminated materials and local industrial activities. Concentrations are measured. In this paper the peaks over threshold method was useful for finding extremes for spatially uncorrelated variables, whereas conditional simulations applied in particular to areas with spatial dependence.

Animals↗

Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants.

The effects of mechanical injury on the metabolism of cartilage matrix are of interest for understanding the pathogenesis of osteoarthrosis and the development of strategies for cartilage repair. The purpose of the present study was to examine the effects of injury on matrix turnover in a calf articular cartilage explant system for which the effects of mechanical loading on cell activity and the cell-mediated pathways of matrix metabolism are already well characterized. New methods of quantitative autoradiography were used in combination with established biochemical and biomechanical techniques for the analysis of cell and matrix responses to acute mechanical injury, with particular attention to the processes of localized matrix turnover in the cell-associated matrices of individual chondrocytes. Matrix deposition and turnover around cells in control explants was spatially dependent, with the highest rates of proteoglycan deposition and turnover and the lowest rates of collagen deposition (as indicated by [3H]proline autoradiography) occurring in the pericellular matrix. Injurious compression was associated with (a) an abrupt decrease in the tensile load-carrying capacity of the collagen matrix, apparently associated with mechanical failure of the tissue, (b) a considerable but subtotal decrease in cell viability, marked by the emergence of an apparently inactive cell population interspersed within catabolically active but abnormally large cells, and (c) sustained, elevated rates of proteoglycan turnover, particularly in the cell-associated matrices of apparently viable cells, which involved the increased release of aggregating species in addition to a spectrum of degradation fragments that were also in controls. These results may represent an in vitro model for the responses of chondrocytes and the cartilage extracellular matrix to mechanical injury.

Animals↗

High-flux signals and spatial localization in high-resolution 1H spectroscopy with surface coils.

To perform in vivo localized proton spectroscopy with water suppression, spin-echo sequences, made of binomial pulses, are commonly used with surface coils. The frequency selective response to such a sequence is also-spatially dependent, that is dependent on the sample shape and on the pulse angle adjustment. It is consequently pointed out in this paper that quantitative analysis for relative peak intensities may be strongly affected by the contribution of the high-flux regions. In vivo proton spectroscopy of rat brain exemplifies this difficulty. It is shown that the use of selective prepulses to suppress high-flux signals may be of poor efficiency depending on chemical shift, while the use of hard nonselective prepulses works for any chemical shift.

Animals↗

Intensity artifacts in MRI caused by gradient switching in an animal-size NMR magnet.

The switching of magnetic field gradients in MRI gives rise to eddy currents in the structural components of superconducting magnet systems. The associated magnetic fields cause intensity artifacts which are particularly severe in some animal-size systems. We treat theoretically three mechanisms which cause intensity artifacts in one-dimensional projection images obtained by a spin-echo technique. The first is an off-resonance effect, caused by applying the refocusing pulse before the read compensation gradient pulse has decayed sufficiently. The other two mechanisms are caused by a spatial dependence of the phase accumulated by the spins at the time of formation of the echo, as a result of the eddy current fields. First, interference causes a loss of transverse magnetization because of a variation in the phase of spins which lie on the same isochromat during the read gradient pulse. Second, a variation of the phase of the spins in a direction orthogonal to the isochromats causes spins throughout the sample to refocus at different times. These two mechanisms are fundamentally different, since interference can occur even if the main magnetic field is homogeneous, whereas improper refocusing does not. It is shown that there is no loss of intensity by the interference mechanism if phase encoding is used to form two-dimensional images. This may well be a major reason why images obtained by 2DFT have been found to be generally superior to those obtained by projection reconstruction. Experimentally, the distribution of intensity in one-dimensional projection images of a square slice phantom is compared with theoretical intensities, estimated using eddy current field reported in the preceding paper.

Artifacts↗

In vivo proton spectroscopy and spectroscopic imaging of [1-13C]-glucose and its metabolic products.

Metabolism of [1-13C]-glucose was studied in situ in cat brain using gradient-enhanced proton-detected heteronuclear spectroscopy. Proton detection of [1-13C]-glucose, [3-13C]-lactate, 4-[13C]-glutamine, 4-[13C]-glutamate and the combined signals 2-[13C]-glutamate/glutamine and 3-[13C]-glutamate/glutamine was achieved, despite the fact that some of the associated proton resonances are close to the water signal. Two-dimensional [1H-13C]-spectra demonstrate the possibility of in situ spectral assignment with 1H sensitivity and 13C resolution. Spectroscopic images of glucose and its metabolic products were also acquired, showing the possibility to study spatial dependence of metabolism.

Animals↗

Quantitative characterization of the eddy current fields in a 40-cm bore superconducting magnet.

The temporal and spatial dependence of the eddy current fields, generated by switching off x, y, and z gradients in a 40-cm bore Bruker superconducting magnet, have been studied by measuring the offset frequency of the proton FID obtained from a small spherical sample. The measurements were made with the pre-emphasis unit deactivated. The data obtained at each location were well fitted to a sum of four exponentially decaying components. The shortest decay is, in each case, associated with the decay of the current in the gradient coil itself, while the other decays are associated with three eddy currents with decay times ranging from 13 to 480 ms. Each of the three eddy currents generates an essentially uniform gradient for at least 4 cm on either side of the isocenter. However, when the eddy currents are generated by either the vertical transverse gradient or the longitudinal gradient, the eddy current gradients are also accompanied by a field shift.

Magnetic Resonance Imaging↗

Surface coil cardiac tagging and 31P spectroscopic localization with B1-insensitive adiabatic pulses.

A technique is presented for MRI tagging in the presence of inhomogeneous B1 fields. A rectangular tagging grid is produced with B1-insensitive adiabatic pulses in a magnetization preparation period that precedes image acquisition. Phantom results demonstrate that the method is well-suited to surface coil experiments. The technique is applied to a canine model of myocardial ischemia to track the spatially dependent wall motion of the left ventricle during the cardiac cycle. Transmural 31P spectra are acquired from the same double-tuned surface coil, with tagging and spectroscopy performed for the first time, during normal, ischemic, and recovery conditions for the same animal.

Adenosine Triphosphate↗

Calculation of sensitivity correction factors for surface coil MRS.

Quantification of MRS signals obtained with surface coils is difficult due to the inhomogeneous response of these coils. This inhomogeneity results in the measured signal from a defined volume of interest (VOI) being spatially dependent. To account for the sensitivity variation with position from the surface coil, we have developed a method of calculating correction factors for defined VOIs based on an experimentally obtained 3D sensitivity coil map. These factors may then be applied to spectra obtained from these VOIs to accurately take into consideration the varying coil sensitivity resulting in a reduction of measured signal. This method is demonstrated here to be able to correct for the inhomogeneity of surface coils over a range of two coil radii to within 4% accuracy.

Humans↗

Theory of heterogeneous relaxation in compartmentalized tissues.

A new model of compartmentalized relaxation--that which occurs for spins (protons) exchanging between compartments of different relaxation rates--is presented. This model generalizes previous ones by allowing spatially dependent relaxation within compartments. Solutions for the diffusion-Bloch equations are found via an efficient numerical technique known as the generalized moment expansion, and they agree well with the solutions to the standard two-site exchange equations (TSEE) for many typical situations. Specific models are developed for liposomes, red blood cells, capillaries, and arteries with respect to applied contrast agents. A parameter derived from tissue characteristics is introduced to predict the nature of the solutions. A new method is proposed for using contrast agents to detect capillaries, which exploits their high surface-to-volume ratio relative to the other elements of the vasculature.

Arteries↗

Concomitant gradient terms in phase contrast MR: analysis and correction.

Whenever a linear gradient is activated, concomitant magnetic fields with non-linear spatial dependence result. This is a consequence of Maxwell's equations, i.e., within the imaging volume the magnetic field must have zero divergence, and has negligible curl. The concomitant, or Maxwell field has been described in the MRI literature for over 10 years. In this paper, we theoretically and experimentally show the existence of two additional lowest-order terms in the concomitant field, which we call cross-terms. The concomitant gradient cross-terms only arise when the longitudinal gradient Gz is simultaneously active with a transverse gradient (Gx or Gy). The effect of all of the concomitant gradient terms on phase contrast imaging is examined in detail. Several methods for reducing or eliminating phase errors arising from the concomitant magnetic field are described. The feasibility of a joint pulse sequence-reconstruction method, which requires no increase in minimum TE, is demonstrated. Since the lowest-order terms of the concomitant field are proportional to G2/B0, the importance of concomitant gradient terms is expected to increase given the current interest in systems with stronger gradients and/or weaker main magnetic fields.

Artifacts↗

Quantitative spectroscopic imaging of the human brain.

A method to provide B1 correction and cerebrospinal fluid (CSF) referencing is developed and applied to spectroscopic imaging of the human brain at 4.1 T using a volume head coil. The B1 image allows rapid determination of the spatially dependent B1 that is then used to compensate for the B1 sensitivity of the spectroscopic sequence. The reference signal is acquired from CSF located in a lateral ventricular position using a point-resolved echo spectroscopy (PRESS) acquisition. The CSF spectrum is also corrected for B1 dependence. Together with T2 and T1 corrections, this method is used to provide quantitative values of N-acetylaspartate (NAA), creatine (Cr), and choline (Ch). The metabolite concentrations obtained from a spectroscopic imaging slice through the ventricles in seven normal controls are in good agreement with previously published literature values. This method is applied in a patient with secondary progressive multiple sclerosis, showing separate areas of abnormalities in both NAA and Cr.

Aspartic Acid↗

Disease mapping using empirical Bayes and Bayes methods on mortality statistics in The Netherlands.

Data from the 64 public health service districts in the Netherlands, describing the health status of the Dutch population, were used to construct maps for several causes of deaths. The choice and estimation of the relative risk measure is described. The prior expected number of deaths was modelled using a Poisson regression approach based on a model with main effects of district and age. Desirable properties of risk parameters for disease mapping are that they both reflect the level of risk and cope with the instability in the observed measure caused by the numbers at risk in each district. Different techniques for estimation of parameters were applied: empirical Bayes estimation (EB) using a nonparametric prior and a gamma prior, and a Bayesian approach (B) with a uniform prior. For the parametric EB also a constrained estimator was used. The EB techniques studied in this paper shift or smooth the values of the risk parameter towards a global mean. In the Bayesian method applied here, spatial dependence among districts can be modelled, that is the estimates are smoothed towards a local mean. The three EB estimates gave by and large similar results, although the constrained EB estimate smoothed less, as was expected. The Bayesian estimates smoothed the estimates more or less similarly to the constrained EB.

Bayes Theorem↗

Estrogen-mediated structural and functional synaptic plasticity in the female rat hippocampus.

Light and electron microscopic studies have shown that ovarian steroids regulate the density and number of excitatory synaptic inputs to hippocampal pyramidal cells in the adult female rat; elevated levels of estradiol are associated with a higher density of dendritic spine synapses on CA1 pyramidal cells. Electrophysiological analyses indicate that these hormone-induced synapses increase hippocampal excitability as well as the potential for synaptic plasticity. Importantly, correlation of dendritic spine density and sensitivity to synaptic input of individual CA1 pyramidal cells from estradiol-treated and control animals suggests that synapses induced by estradiol may be a specialized subpopulation that contains primarily the NMDA subtype of glutamate receptor. The apparent NMDA receptor specificity of these synapses may be key to understanding their functional significance. Currently, the behavioral consequences of additional spine synapses are unknown. Numerous studies have aimed at correlating hormone-induced changes in hippocampal connectivity with differences in hippocampus-dependent spatial learning ability in mazes, but the results of these efforts have been equivocal. Anatomical, electrophysiological, and behavioral studies of estradiol-mediated hippocampal plasticity are reviewed. In conclusion, it is suggested that standard behavioral tests of hippocampal function are not sufficient to reveal the behavioral consequences of hormone-induced hippocampal plasticity. Rather, understanding the behavioral consequences of estradiol and progesterone effects on hippocampal connectivity may require analysis of the hippocampus' cognitive and spatial information processing functions in relation to alternative biologically relevant behaviors. A (nonexclusive) proposal that hormone-induced hippocampal plasticity may facilitate appropriate prepartum/maternal behavior is discussed.

Animals↗

Pulsed field gradients in simulations of one- and two-dimensional NMR spectra.

A method for the inclusion of the effects of z-axis pulsed field gradients in computer simulations of an arbitrary pulsed NMR experiment with spin (1/2) nuclei is described. Recognizing that the phase acquired by a coherence following the application of a z-axis pulsed field gradient bears a fixed relation to its order and the spatial position of the spins in the sample tube, the sample is regarded as a collection of volume elements, each phase-encoded by a characteristic, spatially dependent precession frequency. The evolution of the sample's density matrix is thus obtained by computing the evolution of the density matrix for each volume element. Following the last gradient pulse, these density matrices are combined to form a composite density matrix which evolves through the rest of the experiment to yield the observable signal. This approach is implemented in a program which includes capabilities for rigorous inclusion of spin relaxation by dipole-dipole, chemical shift anisotropy, and random field mechanisms, plus the effects of arbitrary RF fields. Mathematical procedures for accelerating these calculations are described. The approach is illustrated by simulations of representative one- and two-dimensional NMR experiments.

Anisotropy↗

Computer simulation of the spin-echo spatial distribution in the case of restricted self-diffusion.

This article concerns the question of a proper stochastic treatment of the spin-echo self-diffusion attenuation of confined particles that arises when short gradient pulse approximation fails. Diffusion is numerically simulated as a succession of random steps when motion is restricted between two perfectly reflecting parallel planes. With the magnetic field gradient perpendicular to the plane boundaries, the spatial distribution of the spin-echo signal is calculated from the simulated trajectories. The diffusion propagator approach (Callaghan, "Principles of Nuclear Magnetic Resonance Microscopy," Oxford Univ. Press, Oxford, 1991), which is just the same as the evaluation of the spin-echo attenuation by the method of cumulant expansion in the Gaussian approximation, with Einstein's approximation of the velocity correlation function (VCF) (delta function), agrees with the results of simulation only for the particle displacements that are much smaller than the size of the confinement. A strong deviation from the results of the simulation appears when the bouncing rate from the boundaries increases at intermediate and long gradient sequences. A better fit, at least for intermediate particle displacements, was obtained by replacing the VCF with the Oppenheim--Mazur solution of the Langevin equation (Oppenheim and Mazur, Physica 30, 1833--1845, 1964), which is modified in a way to allow for spatial dependence of particle displacements. Clearly, interplay of the correlation dynamics and the boundary conditions is taking place for large diffusion displacements. However, the deviation at long times demonstrates a deficiency of the Gaussian approximation for the spin echo of diffusion inside entirely closed pores. Here, the cumulants higher than the second one might not be negligible. The results are compared with the experiments on the edge enhancement by magnetic resonance imaging of a pore.

Journal Article↗

A new model for bacterial growth in heterogeneous systems.

A general theory of spatially dependent bacterial growth in heterogeneous systems is developed by combining a structured-cell kinetic model of bacterial metabolism with reaction-diffusion equations describing the transport of nutrients in the growth medium. Rate constants in the theory are determined for Listeria monocytogenes by fitting the viable count batch growth data acquired in homogeneous, shake-flask cultures. The rate constants are then used to calculate the form of bacterial growth when it occurs as localized microcolonies in structured systems. The same theory is used to analyse the effects of transient variations in environmental variables.

Bacteriological Techniques↗

A Model for the Propagation of Action Potentials in Non-Uniformly Excitable Media.

Electrophysiological properties of cardiac tissue change as a function of position. We define the "excitability" as the propagation velocity of an excitation pulse through the tissue, and study a simple FitzHugh-Nagumo (FHN) model of heart tissue whose excitability changes with position. The propagation velocity is shown to be a good continuous measure of the excitability for both limit cycle and excitable tissue. The influence of the spatial dependence of the excitability is examined for several normal and pathological situations. A novel transient effect is observed for a train of pulses propagating across an excitability step. Copyright 1999 Academic Press.

Journal Article↗