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PubMed1998

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↗

PubMed1998

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↗

PubMed1993

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↗

PubMed1998

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↗

PubMed1999

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↗

PubMed2001

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↗

PubMed1994

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↗

PubMed1999

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↗

PubMed1993

DNA damage in non-proliferating cells subjected to ionizing irradiation at high or low dose rates.

Ionizing radiation damage to the genome of a non-cycling mammalian cell is analyzed using continuous time Markov chains. Immediate damage induced by the radiation is modeled as a batch Poisson arrival process of DNA double strand breaks (DSBs). Different kinds of radiation, for example gamma rays or alpha particles, have different batch probabilities. Enzymatic modulation of the immediate damage is modeled as a Markov process similar to the processes described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete exchange model, which postulates that radiation induced DSBs can subsequently either undergo enzymatically mediated repair (restitution) or can participate pairwise in chromosome exchanges, some of which make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. A complete solution of the Markov chain is known for the case that the exchange rate constant is negligible so that no irremediable chromosome lesions are produced and DSBs are the only damage to the genome. Using PDEs for generating functions, a perturbation calculation is made assuming the exchange rate constant is small compared to the repair rate constant. Some non-perturbative results applicable to very prolonged irradiation are also obtained using matrix methods: Perron-Frobenius theory, variational methods and numerical approximations of eigenvalues. Applications to experimental results on expected values, variances and statistical distributions of DNA lesions are briefly outlined. Continuous time Markov chain models are the most systematic of those current radiation damage models which treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g. ignore diffusion limitations). They contain most other homogeneous models as special cases, limiting cases or approximations. However, applying the continuous time Markov chain models to studying spatial dependence of DSB interactions, which is generally believed to be very important in some situations, presents difficulties.

Animals↗

PubMedDate not supplied

Characteristics of fatty acid-binding proteins and their relation to mammary-derived growth inhibitor.

Based on sequence relationships the cytoplasmic fatty acid-binding proteins (FABPs) of mammalian origin are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-type. Highly conserved sequences of FABPs within the same type correlate with immunological crossreactivities. Isoforms of hepatic-type FABP are found in several mammalian species and for bovine liver FABP specific shifts in isoelectric points upon lipidation with fatty acids are observed. Isoforms of intestinal-type FABP are not known and the occurrence of cardiac-type isoforms so far is confined to bovine heart tissue. A bovine mammary-derived growth inhibitor (MDGI) is 95% homologous to the cardiac-type FABP from bovine heart. Dissociation constants of FABP/fatty acid complexes are in the range of 1 microM and 1:1 stoichiometries are usually found, but the neutral isoform of hepatic FABP from bovine liver binds 2 fatty acids. On subcellular levels hepatic- and cardiac-type FABPs are differently distributed. Though mainly cytosolic in either case, immunoelectron microscopy as well as a gelchromatographic immunofluorescence assay demonstrate the association of hepatic FABP in liver cells with microsomal and outer mitochondrial membranes and with nuclei, whereas in heart cells cardiac FABP is confined to mitochondrial matrix and nuclei. In mammary epithelial cells MDGI is associated with neither mitochondria nor endoplasmic reticulum, and is expressed in a strictly developmental-dependent spatial and temporal pattern. The specific role proposed for MDGI is to arrest growth of mammary epithelial cells when they become committed to differentiation in the mammary gland.

Amino Acid Sequence↗

PubMed1992

Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region.

We present a model for predicting the temporal and spatial dependence of [Ca] in the cardiac subsarcolemmal diadic region (cleft), following Ca release from the "feet" of the sarcoplasmic reticulum. This region is modeled as a disc 10 nm thick, 430 nm in radius, with or without Ca binding sites and open at its periphery to the cytosol. [Ca] is computed for three diffusion coefficients (100, 20 and 4% of aqueous diffusion), following release of a 20-msec square pulse sufficient to produce 50% maximal contractile force, or repetitive release (400/min) of such pulses. Numerical solutions are obtained for the general diffusion/binding problem and analytic solutions for the case of no binding sites. For the middle value of diffusion coefficient, and in the absence of binding sites, [Ca] rises to approximately 1.5 mM in 20-msec and then falls to approximately 0.1 microM in less than 3 msec. Adding binding sites reduces peak [Ca] to approximately 0.6 mM but prolongs its decline, requiring approximately 200 msec to reach 20 microM. For repetitive release [Ca] is greater than 100 microM for roughly half of each cycle. Two major implications of the predicted [Ca] are: (i) The effect of Ca binding sites on [Ca] will cause Ca efflux from the cleft via the Na-Ca exchanger (Km(Ca) approximately 20 microM) to continue at a significant level for greater than 200 msec. (ii) The time constant for inactivation of release from the "feet" must be much greater than for activation if Ca-induced Ca release is to continue for greater than 1-2 msec.

Animals↗

PubMed1989

The asymptotic transectional/circumferential homogeneity of the solutions of reaction-diffusion systems in/on cylinder-like domains.

It is often reported that an animal with spotty coat markings on its body has a tail with stripe-shaped pattern. In other various biological and chemical phenomena in/on cylinder-like domains, longitudinally periodic band patterns are observed much more often than the other non-uniform patterns. This paper mathematically explains these observations by proving that, in/on a long and narrow cylinder-like domain, any solution of reaction-diffusion system asymptotically loses its spatial dependence in the transectional/circumferential direction.

Animals↗

PubMed1985

Mechanics of the transduction of sound in the tympanal organ of adults and larvae of locusts.

The mechanical transmission of sound in the tympanal organ of adults and 5th instar larvae of Locusta migratoria and Schistocerca gregaria has been investigated by means of stroboscopic measurements within a frequency range from 1-20 kHz. Frequency dependent spatial distributions of amplitudes and phases of oscillation on the tympanal membrane and the Müller's organ could be demonstrated. Cuticular structures on the membrane may act as a lever arm (e.g. elevated process) and cause a transformation of the (unidimensional) membrane motion into components of displacements in the Müller's organ perpendicular, as well as even parallel, to the membrane. Sites of maximum relative displacements at distinct frequencies are found to be correlated to the course of the dendrites of the acoustic receptor cells. Differences in morphology of the tympanal organ between the two species as well as between adults and larvae always correspond to differences in the mechanical properties (resonances etc.). Consequently, differences or changes in the neurophysiological response characteristics of the different receptor cells have been found. Based upon these findings a correlation between the anatomical and physiological classification of the receptor cell groups is presented.

Animals↗

PubMed1999

Two-dimensional deghosting for EPI.

A residual ghost artefact in echo-planar imaging (EPI) remains after the standard correction procedure based on a 1-dimensional phase-modulation of the spectra of even or odd echoes. A better reduction of this artefact is demonstrated using a 2-dimensional phase correction. The phase correction map is measured inside the ghost-free region of the image, preferably in a reference scan with an increased field of view, as the phase difference between complex images reconstructed separately from even and odd echoes. An extrapolated map consisting of spatial components up to the second order (constant, x, y, xy and x2-y2) is then found by a fit to the measured values. This map is used to correct the phase of even- and odd-reconstructed images before adding them. This procedure may cause some spatially dependent loss of signal, but if the level of the residual artefact is less than 20% of the image intensity, such losses are negligible.

Artifacts↗

PubMed2002

Microscopic spin tagging (MiST) for flow imaging.

In this study, a new strategy for slow flow imaging is proposed. The basic idea is to generate flow contrast on a microscopic level below the spatial resolution of an imaging experiment. Since a microscopic spin tagging scheme is used, this concept is called MiST (Microscopic Spin Tagging). MiST is not a single specific measurement sequence, but rather a new flow sensitive preparation concept which is highly flexible and can be carried out in many ways. The common principle in all possible realizations of MiST is a periodic tagging of magnetization in thin planes (100-200 microm) within the imaging voxels by means of spatially selective RF-pulses. Therefore, flow sensitivity occurs via inflow of fresh spins on a microscopic scale. With this approach, short evolution times are sufficient to introduce inflow contrast and a spatial dependence of inflow times is avoided. The flow sensitive preparation and image orientation are also not connected as they are in conventional time-of-flight techniques. Another powerful feature of MiST is that it can be designed as a non-subtraction method, which results in no signal from stationary spins. Here we present a first realization of the MiST concept and its validation in quantitative flow measurements to demonstrate the feasibility of the proposed preparation concept.

Arteries↗

PubMed2002

Visual-tactile spatial interaction in saccade generation.

Saccadic reaction times to visual targets tend to be faster when non-visual stimuli are presented in close temporal or spatial proximity even if subjects are instructed to ignore the accessory input. The effect tends to decrease with increasing spatial distance between the stimuli. Multisensory interaction effects measured in neural structures involved in saccade generation have demonstrated a similar spatial dependence. The present study investigated visual-tactile interaction effects on saccadic reaction time using a focused attention paradigm. Compared to unimodal visual targets saccadic reaction time to bimodal stimuli was reduced by up to 30 ms. The effect was larger for ipsi- than for contralateral presentations, and it increased with the eccentricity of the visual target. The results are consistent with attributing part of the facilitation to a multisensory effect of bimodal neurons with overlapping visual and tactile receptive field structures in the deep layers of the superior colliculus.

Adaptation, Physiological↗

PubMed1997

Suitability of cerebrospinal fluid as a signal-intensity reference on MRI: evaluation of signal-intensity variations in the lumbosacral dural sac.

The suitability of the cerebrospinal fluid (CSF) in the lumbosacral dural sac as an internal signal-intensity reference was studied on magnetic resonance imaging (MRI) of the lumbar spine using a surface coil and motion artefact suppression technique. A signal-intensity reference is needed when signal is compared between images, studies or subjects. Homogeneity of the CSF was estimated visually on T2-weighted images of 60 subjects at 1.5 T and of another 60 subjects at 0.1 T. Spines with a severely narrowed dural sac or marked scoliosis were excluded from the study to avoid partial volume effect. CSF was homogeneous in 82% and 73% of the examinations at 1.5 T and 0.1 T, respectively. The type and location of the local inhomogeneities did not relate to local narrowings of the dural sac. The signal intensity of CSF was measured in 108 examinations at 0.1 T after correcting the spatially-dependent signal-intensity non-uniformities with a phantom-based method. The signal-intensity difference between the CSF in the upper and lower lumbar dural sac was less than 10% in 73% of the examinations. The CSF in the lumbosacral dural sac can be a useful signal-intensity reference for estimation of the signal of the adjacent structures in patients without severe narrowing of the dural sac or marked scoliosis. It may contribute to assessing spinal disease processes.

Adult↗

PubMed2001

A prototype high-resolution animal positron tomograph with avalanche photodiode arrays and LSO crystals.

To fully utilize positron emission tomography (PET) as a non-invasive tool for tissue characterization, dedicated instrumentation is being developed which is specially suited for imaging mice and rats. Semiconductor detectors, such as avalanche photodiodes (APDs), may offer an alternative to photomultiplier tubes for the readout of scintillation crystals. Since the scintillation characteristics of lutetium oxyorthosilicate (LSO) are well matched to APDs, the combination of LSO and APDs seems favourable, and the goal of this study was to build a positron tomograph with LSO-APD modules to prove the feasibility of such an approach. A prototype PET scanner based on APD readout of small, individual LSO crystals was developed for tracer studies in mice and rats. The tomograph consists of two sectors (86 mm distance), each comprising three LSO-APD modules, which can be rotated for the acquisition of complete projections. In each module, small LSO crystals (3.7 x 3.7 x 12 mm3) are individually coupled to one channel within matrices containing 2x8 square APDs (2.6 x 2.6 mm2 sensitive area per channel). The list-mode data are reconstructed with a penalized weighted least squares algorithm which includes the spatially dependent line spread function of the tomograph. Basic performance parameters were measured with phantoms and first experiments with rats and mice were conducted to introduce this methodology for biomedical imaging. The reconstructed field of view covers 68 mm, which is 80% of the total detector diameter. Image resolution was shown to be 2.4 mm within the whole reconstructed field of view. Using a lower energy threshold of 450 keV, the system sensitivity was 350 Hz/MBq for a line source in air in the centre of the field of view. In a water-filled cylinder of 4.6 cm diameter, the scatter fraction at the centre of the field of view was 16% (450 keV threshold). The count rate was linear up to 700 coincidence counts per second. In vivo studies of anaesthetized rats and mice showed the feasibility of in vivo imaging using this PET scanner. The first LSO-APD prototype tomograph has been successfully introduced for in vivo animal imaging. APD arrays in combination with LSO crystals offer new design possibilities for positron tomographs with finely granulated detector channels.

Animals↗