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PubMed1994

Health and infarcted brain tissues studied at short diffusion times: the origins of apparent restriction and the reduction in apparent diffusion coefficient.

The significance of NMR water diffusion measurements performed at short diffusion times (< 10 ms) for brain tissue is examined. An apparent restriction to diffusion for both healthy and cytotoxically edematous tissue is shown: cytotoxic edema lengthens the diffusion time at which this phenomenon is visible. The dramatic reduction in apparent diffusion coefficient (ADC) observed in the core of cytotoxic edema is explained in terms of the enclosure of extracellular water in non-contiguous pockets in conjunction with the shift of water from the extra-to the intracellular space. The model presented provides an explanation for the ADC reduction without recourse to changes in the cell membrane permeability to water, or unrealistic values for the extra- and intracellular diffusion coefficients.

Animals↗

PubMed2005

A diffusion tensor imaging analysis of gender differences in water diffusivity within human skeletal muscle.

The diffusive properties of adjacent muscles at rest were evaluated in male (n = 12) and female (n = 12) subjects using diffusion tensor imaging (DTI). The principle, second and third eigenvalues, trace of the diffusion tensor [Tr(D)], and two anisotropic parameters, ellipsoid eccentricity (e) and fractional anisotropy (FA), of various muscles in the human calf were calculated from the diffusion tensor. Seven muscles were investigated in this study from images acquired of the left calf: the soleus, lateral gastrocnemius, medial gastrocnemius, posterior tibialis, anterior tibialis, extensor digitorum longus and peroneus longus. A mathematical model was also derived that relates the eigenvalues of the diffusion tensor to the muscle fiber volume fraction, which is defined as the volume of muscle fibers within a well-defined arbitrary muscle volume. Females on average had higher eigenvalues and Tr(D) compared with males, with the majority of muscles being statistically different between the sexes. In contrast, males on average had higher e and FA than females, with the large plantar flexors--soleus, lateral gastrocnemius, and medial gastrocnemius--producing statistically different results. The behavior of the mathematical model for variations in fiber volume fraction produced similar trends to those seen when the experimental data were fit to the model. The model predicts that a larger volume fraction of skeletal muscle in males is devoted to fibers than in females, but the true underlying source of the gender discrepancy remains unclear. Although the model does not fully account for other transport processes, it does provide some insight into the limiting factors that affect the diffusion of water in skeletal muscle measured by DTI.

Adult↗

PubMed2003

Oxygen diffusion coefficient and oxygen permeability of metmyoglobin solutions determined in a diffusion chamber using a non-steady state method.

Non-steady state measurements of oxygen diffusion through various model layers can be performed using a diffusion chamber that was described earlier [1, 2]. A closer analysis of these measurements showed that they not only yield the oxygen diffusion coefficient (DO2) of the diffusion layer, but also the oxygen permeability (PO2). In this study DO2 and PO2 have been determined in solutions of metmyoglobin (metMb) with concentrations varying between 5 and 40 g/dL at 25 degrees C. Both DO2 and PO2 decreased with increasing metMb concentration. This decrease was comparable to the values reported for DO2 in protein solutions by Kreuzer and Hoofd [3]. Using this diffusion chamber for non-steady state measurements, oxygen diffusion coefficients, oxygen permeability and oxygen solubility (aO2 = PO2/DO2) of various model layers could be determined.

Diffusion↗

PubMed1984

Dual role of diffusion in tissue gas exchange: blood-tissue equilibration and diffusion shunt.

The role of diffusion in tissue gas exchange is investigated using a simple mathematical model which incorporates both tissue-blood equilibration and gas transfer between arterial and venous vessels with counter-current flow, leading to 'diffusion shunt'. Both increasing the diffusion coefficient of the gas considered or decreasing the blood flow results in two antagonistic effects: (i) improvement of blood/tissue equilibration, (ii) increase in extent of diffusion shunt. The diffusion shunt retards inert gas wash-out (local tissue clearance) and leads thus, if not taken into account, to an underestimation of capillary blood flow calculated from the wash-out rate constant. For O2 (and CO2) the diffusion shunt reduces the efficacy of blood/tissue transfer, but its extent is expected to be only moderate because of the chemical combination of these gases in blood.

Diffusion↗

PubMed1994

Effect of surfactants on the diffusion coefficients of proteins, measured by analytical SPLITT fractionation (ASF) in the diffusion mode.

This work reports further studies of protein transport parameters in the new technique called analytical SPLITT fractionation. The SPLITT fractionation channel mimics a dialysis-like separation utilizing differential transport across an ultra-thin lamina flowing through a channel. The flowing stream is split into two sub-streams at the channel outlet, between which the protein is distributed. The cell is capable of rapidly measuring diffusion coefficients of proteins, based on their differential transport across the channel thickness, which affects the distribution between the two outlet sub-streams. The sub-stream next to the sample introduction port is more enriched than the sub-stream at the counter port when the diffusion coefficients is small. The smaller the diffusion coefficient, the higher the degree of retrieval of the protein at the sample side outlet. The entire process is realized within a short time, and a quantitative treatment of the signals of the two sub-streams yields a retrieval factor which is used for the determination of the diffusion coefficient. The conditions under which the selectivity of the diffusion SPLITT cell is optimal were examined. Analytical SPLITT fractionation has proven successful, using a number of proteins under various conditions. Results showed that the technique can detect subtle changes in proteins diffusion coefficients, and confirm that addition of small concentrations of surfactants does not change their transport parameters significantly.

Chromatography, High Pressure Liquid↗

PubMed2006

Anisotropic diffusion of metabolites in peripheral nerve using diffusion weighted magnetic resonance spectroscopy at ultra-high field.

Although the diffusivity and anisotropy of water has been investigated thoroughly in ordered axonal systems (i.e., nervous tissue), there have been very few studies on the directional dependence of diffusion of metabolites. In this study, the mean apparent diffusion coefficient (Trace/3 ADC) and fractional anisotropy (FA) values of the intracellular metabolites N-acetyl aspartate (NAA), creatine and phosphocreatine (tCr), choline (Cho), taurine (Tau), and glutamate and glutamine (Glx) were measured parallel and perpendicular to the length of excised frog sciatic nerve using a water suppressed, diffusion-weighted, spin-echo pulse sequence at 18.8T. The degree of anisotropy (FA) of NAA (0.41+/-0.09) was determined to be less than tCr (0.59+/-0.07) and Cho (0.61+/-0.11), which is consistent with previously reported human studies of white matter. In contrast, Glx diffusion was found to be almost isotropic with an FA value of 0.20+/-0.06. The differences of FA between the metabolites is most likely due to their differing micro-environments and could be beneficial as an indicator of compartment specific changes with disease, information not readily available with water diffusion.

Animals↗

PubMed2005

Applied electric fields accelerate the diffusion rate and increase the diffusion distance of DiI in fixed tissue.

Lipophilic carbocyanine dyes are effective neuronal tracers in fixed tissue. However, their application has been limited by the slow diffusion, short tracing distances, and long durations of incubation in fixed tissue. We used applied dc electric fields, that exerted forces on the cationic dyes, to increase the diffusion velocity and maximal tracing distances of DiI and its analogs. Maximum diffusion distances of DiI in fixed human peripheral nerve were approximately 4 times longer then the previous reported maximum, and diffusion velocities was approximately 100 times faster in samples exposed to the electric field than in control samples. This method enabled retrograde tracing from a distal nerve branch into a proximal nerve trunk, and did not result in lateral transaxonal diffusion. Field enhanced diffusion will expand the range of uses of lipophilic dyes in fixed tissues and enable topographic mapping of peripheral nerve fascicles in post-mortem tissue.

Aged↗

PubMed1993

MRI diffusion-weighted imaging of the brain: contributions to image contrast from CSF signal reduction, use of a long echo time and diffusion effects.

The contributions of CSF signal reduction, use of a long echo time and diffusion weighting to the appearance of pulsed gradient spin echo (PGSE) images are analysed by reference to T2-weighted spin echo and T2-weighted fluid attenuated inversion recovery (FLAIR) pulse sequences. Both PGSE and T2-weighted FLAIR sequences reduce CSF signal and produce very heavy T2 weighting allowing the specific additional contribution produced by the diffusion weighting of PGSE sequences to be recognized. Considerable advantage accrues from CSF suppression with both PGSE and FLAIR sequences through reduction in partial volume effects and artefacts. The very heavy T2 weighting with both these pulse sequences highlights certain white matter tracts and provides high sensitivity to disease. The additional diffusion weighting with PGSE sequences can enhance or reduce white matter tract signals and may enhance or reduce lesion conspicuity relative to the FLAIR sequences. Many of the benefits attributed to the diffusion-weighted PGSE sequence may result from the reduction of the CSF signal and the heavy T2 weighting of the sequence without a contribution from diffusion effects. However, additional anatomical detail, sensitivity to myelination and increased lesion conspicuity may result from the diffusion weighting.

Brain↗

PubMed2002

Focal follicular features in tonsillar diffuse large B-cell lymphomas: follicular lymphoma with diffuse areas or follicular colonization.

Focal follicular features in diffuse large B-cell lymphomas (DLBCLs) are bound to raise the question of follicular lymphoma (FL) with diffuse areas, because the diagnosis of FL is based on the presence of follicular areas, even though focal. We report 7 cases of primary tonsillar DLBCLs with focal follicular features that presented with morphologic, immunohistochemical, and biological features distinct from those of FL. Histologically, these tumors were characterized by involvement of pericryptal follicles with adjacent dominant diffuse areas. Monomorphous large tumor cells were evenly spaced with abundant, often clear cytoplasm, and blastoid nuclei often with a delicate nuclear membrane. Importantly, residual germinal centers (GCs) were present in the form of either an intrafollicular GC remnant or an isolated GC in the midst of diffuse tumor. An extrafollicular and/or parafollicular growth pattern was also observed. Bcl-6 staining revealed a predominantly sporadic occurrence of Bcl-6(+) cells, comprising <50% of tumor cells, and none displayed diffusely dense collections (>75%) of Bcl-6(+) tumor cells characteristic of the GC or FL. Staining for CD10 was negative in 6 cases. Five of 7 patients were younger than 60, the median age of other patients with primary tonsillar DLBCL. No extratonsillar involvement was seen at 18 months after diagnosis. After chemotherapy or radiotherapy, complete remission was achieved with ease in all patients, but 2 patients who were treated with chemotherapy alone relapsed at 24 and 30 months. In conclusion, tonsillar DLBCL includes a small (10%) but distinct subgroup that warrants distinction from FL with predominant diffuse areas or de novo DLBCL. It appears that the focal follicular features in tonsillar DLBCL likely represent follicular colonization of marginal zone B-cell lymphoma, probably high-grade, if the possibility of FL is excluded.

Adult↗

PubMed2006

Diffusion in multilayer media: transient behavior of the lateral diffusion coefficient.

A general formalism for treating lateral diffusion in a multilayer medium is developed. The formalism is based on the relation between the lateral diffusion and the distribution of the cumulative residence time, which the diffusing particle spends in different layers. We exploit this fact to derive general expressions which give the global and local time-dependent diffusion coefficients in terms of the average cumulative times spent by the particle in different layers and the probabilities of finding the particle in different layers, respectively. These expressions are used to generalize two recently obtained results: (a) A solution for the short-time behavior of the lateral diffusion coefficient in two layers separated by a permeable membrane obtained by a perturbation theory is extended to the entire range of time. (b) A solution for the time-dependent diffusion coefficient of a ligand, which repeatedly dissociates and rebinds to sites on a planar surface, obtained under the assumption that the medium above the surface is infinite, is generalized to allow for the medium layer of finite thickness. For the latter problem we derive an expression for the Fourier-Laplace transform of the propagator in terms of the double Laplace transform of the probability density of the cumulative residence time spent by the ligand in the medium layer.

Diffusion↗

PubMed2001

Differential control of cellular gene expression by diffusible and non-diffusible EGF.

Cell gene expression is affected by both the kind and mode of growth factor stimulation (diffusive vs. non-diffusive). Epidermal growth factor (EGF) was pattern-immobilized on a polystyrene plate. Although the growth of the rat phaeochromocytoma cell line PC12 is stimulated by diffusible EGF, and differentiation is stimulated by diffusible nerve growth factor (NGF), immobilized (non-diffusible) EGF stimulated PC12 differentiation. The immobilized EGF caused a long-lasting stimulation of the intracellular signal protein mitogen-associated protein MAP kinase (MAPK, also known as ERK) and p38 (a subfamily of the MAPK superfamily) in cells, as did diffusible NGF. The switching between growth stimulation and differentiation is considered to be due to the duration of the stimulus. The function of the biosignal conjugate was regulated using conjugation methodology.

Animals↗

PubMedDate not supplied

Diffusion-weighted magnetic resonance imaging in radiation-induced cerebral necrosis. Apparent diffusion coefficient in lesion components.

OBJECTIVE: The objective of this retrospective study was to investigate the diffusivity of different components of radiation-induced cerebral necrosis with the hypothesis that the diffusivity of the various components is elevated to different degrees. METHODS: Twenty-two patients (18 men, 4 women, aged 34-72 years) with radiation injury to the temporal lobes after radiation therapy (RT) for nasopharyngeal carcinoma with diagnosis confirmed on serial magnetic resonance imaging (MRI) were studied with coronal T2-weighted, diffusion-weighted, and gadolinium-enhanced MRI. Using three diffusion directions for diffusion-weighted MRI, the apparent diffusion coefficients (ADCs) of the enhanced component, the cystic or liquefied component, and the edema component were measured. RESULTS: ADCs of all components of RT-induced cerebral necrosis (154 +/- 21.6 x 10(-5) mm2/s for contrast-enhanced component; 188 +/- 47.4 x 10(-5) mm2/s for cystic/liquefied component; 177 +/- 35.4 x 10(-5) mm2/s for edema component) were all significantly higher (P<0.00001) than ADC of the normal frontal lobe white matter (82 +/- 12.4 x 10(-5) mm2/s). The ADC of the enhanced component was significantly lower than that of the cystic/liquefied component (P=0.0096) and the edema component (P=0.003). A significantly lower ADC was shown in the enhanced component in temporal lobes showing both short-term morphologic deterioration (P=0.024) and occurrence of deterioration on long-term follow-up (P=0.04) compared with the temporal lobes that showed improvement or stable morphology. CONCLUSIONS: ADCs of the contrast-enhanced component, cystic/liquefied component, and edema in RT-induced cerebral necrosis was significantly higher than in normal brain parenchyma. There is association between a lower ADC in the contrast-enhanced component and morphologic deterioration.

Brain↗

PubMed2002

Systematic derivation of reaction-diffusion equations with distributed delays and relations to fractional reaction-diffusion equations and hyperbolic transport equations: application to the theory of Neolithic transition.

We introduce a general method for the systematic derivation of nonlinear reaction-diffusion equations with distributed delays. We study the interactions among different types of moving individuals (atoms, molecules, quasiparticles, biological organisms, etc). The motion of each species is described by the continuous time random walk theory, analyzed in the literature for transport problems, whereas the interactions among the species are described by a set of transformation rates, which are nonlinear functions of the local concentrations of the different types of individuals. We use the time interval between two jumps (the transition time) as an additional state variable and obtain a set of evolution equations, which are local in time. In order to make a connection with the transport models used in the literature, we make transformations which eliminate the transition time and derive a set of nonlocal equations which are nonlinear generalizations of the so-called generalized master equations. The method leads under different specified conditions to various types of nonlocal transport equations including a nonlinear generalization of fractional diffusion equations, hyperbolic reaction-diffusion equations, and delay-differential reaction-diffusion equations. Thus in the analysis of a given problem we can fit to the data the type of reaction-diffusion equation and the corresponding physical and kinetic parameters. The method is illustrated, as a test case, by the study of the neolithic transition. We introduce a set of assumptions which makes it possible to describe the transition from hunting and gathering to agriculture economics by a differential delay reaction-diffusion equation for the population density. We derive a delay evolution equation for the rate of advance of agriculture, which illustrates an application of our analysis.

Biophysical Phenomena↗

PubMed2002

Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study.

PURPOSE: To evaluate differences in white matter diffusion properties as a function of age in healthy children and adolescents. MATERIALS AND METHODS: Echo-planar diffusion-tensor magnetic resonance (MR) imaging was performed in 33 healthy subjects aged 5-18 years who were recruited from a functional imaging study of normal language development. Results of neurologic, psychologic, and structural MR imaging examinations were within the normal range for all subjects. The trace of the apparent diffusion coefficient and fractional anisotropy in white matter were correlated as a function of age by using Spearman rank correlation. RESULTS: Statistically significant negative correlation of the trace of the apparent diffusion coefficient with age was found throughout the white matter. Significant positive correlation of fractional anisotropy with age was found in the internal capsule, corticospinal tract, left arcuate fasciculus, and right inferior longitudinal fasciculus. CONCLUSION: Diffusion-tensor MR imaging results indicate that white matter maturation assessed at different ages involves increases in both white matter density and organization during childhood and adolescence. The trace of the apparent diffusion coefficient and fractional anisotropy may reflect different physiologic processes in healthy children and adolescents.

Adolescent↗

PubMed2004

Diffusing capacity reexamined: relative roles of diffusion and chemical reaction in red cell uptake of O2, CO, CO2, and NO.

This paper presents an analytical expression for the diffusing capacity (Theta(t)) of the red blood cell (RBC) for any reactive gas in terms of size and shape of the RBC, thickness of the unstirred plasma layer surrounding the RBC, diffusivities and solubilities of the gas in RBC and boundary layer, hematocrit, and the slope of the dissociation curve. The expression for Theta(t) has been derived by spatial averaging of the fundamental convection-diffusion-reaction equation for O(2) in the RBC and has been generalized to all cell shapes and for other reactive gases such as CO, NO, and CO(2). The effects of size and shape of the RBC, thickness of the unstirred plasma layer, hemoglobin concentration, and hematocrit on Theta(t) have been analyzed, and the analytically obtained expression for Theta(t) has been validated by comparison with different sets of existing experimental data for O(2) and CO(2). Our results indicate that the discoidal shape of the human RBC with average dimensions of 1.6-mum thickness and 8-mum diameter is close to optimal design for O(2) uptake and that the true reaction velocity in the RBC is suppressed significantly by the mass transfer resistance in the surrounding unstirred layer. In vitro measurements using rapid-mixing technique, which measures Theta(t) in the presence of artificially created large boundary layers, substantially underpredicts the in vivo diffusing capacity of the RBC in the diffusion-controlled regime. Depending on the conditions in the RBC, uptake of less reactive gases (such as CO) undergoes transition from reaction-limited to diffusion-limited regime. For a constant set of morphological parameters, the theoretical expression for Theta(t) predicts that Theta(t,NO) > Theta(t,)(CO(2)) > Theta(t,)(O(2)) > Theta(t,CO).

Animals↗

PubMed2003

Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality.

OBJECTIVE: The most common finding on magnetic resonance imaging (MRI) of the brain in preterm infants at term-equivalent age is diffuse excessive high signal intensity (DEHSI) in the white matter. It is unclear whether DEHSI represents a biological abnormality. This study used diffusion-weighted imaging (DWI) to compare apparent diffusion coefficient (ADC) values in DEHSI with infants with normal imaging and those with overt brain damage to determine whether DEHSI shows the diffusion characteristics of normal or abnormal tissue. METHODS: MRI, using conventional and diffusion-weighted imaging (DWI), was performed in 50 preterm infants at term-equivalent age using a 1.5 Tesla MR scanner. The infants were divided into 3 groups on the basis of their MRI results: 1) normal white matter, 2) DEHSI, or 3) overt white matter pathology. ADC values were measured in the frontal, central, and posterior white matter at the level of the centrum semiovale. ADC values in the 3 groups of preterm infants were compared using a 1-way analysis of variance with a Bonferroni test for multiple comparisons. RESULTS: ADC values were significantly higher in infants with DEHSI and infants with overt white matter pathology than in infants with normal white matter. There was no significant difference between ADC values in infants with DEHSI and those with overt white matter pathology. CONCLUSIONS: This study provides objective evidence that DEHSI represents diffuse white matter abnormality.

Body Water↗

PubMed1997

Studies on diffusion in alginate gels. II. Effect of acid and subsequent re-exposure to calcium on the diffusion of caffeine and theophylline in alginate gel films.

The aim of this research was to investigate the effect of acid exposure and calcium re-exposure on the diffusion of caffeine and theophylline through calcium alginate gel films. Diffusion was measured using side-by-side glass cells, before and after the films were exposed to simulated gastric fluid (SGF) USP minus pepsin. The permeability increased by about 15-fold for theophylline and 48-fold for caffeine after 5 min SGF exposure. There was no significant further increase by prolonging the exposure time to 4 hr. The diffusion of both drugs was less than through alginate gel films that were not cross-linked with calcium but were gelled in SGF. Treatment of the calcium alginate gel films with SGF depleted the films of all of their calcium content. Calcium alginate gel films that were exposed to SGF for a constant period of 15 min, were re-exposed to 0.34 M calcium chloride solution for periods up to 24 hr. The calcium content returned to 80% of the level in the original calcium alginate films and diffusion was reduced, but not to the level that was observed in the original calcium alginate films. It was concluded that the effect of SGF on calcium alginate was very rapid and that the increase in drug diffusion observed was probably due to removal of calcium from the gel. It was also concluded that the original diffusion properties and calcium content could only be partially regenerated by re-exposing the acid-exposed films to calcium chloride.

Administration, Oral↗

PubMed1999

[Diffusion MRI and cerebral ischemia. When to calculate the coefficient of diffusion?].

INTRODUCTION: There are two types of diffusion images: so-called "diffusion-weighted" images (DWI) and apparent diffusion coefficient (ADC) images. For certain authors, ADC mapping is crucial for interpreting diffusion images while for others the ADC map adds no further sensitivity or specificity compared with diffusion weighted images. The objective of this work was to determine those situations where ADC mapping modifies image interpretation. MATERIAL AND METHODS: T2-weighted and diffusion-weighted (DIF) MRI sequences were acquired in 197 patients with suspected cerebral ischemia (< or = 48 hr). For each lesion (239 lesions in the 197 patients), we analyzed MRI interpretation with and without ADC mapping and compared the interpretations with the final diagnosis established on clinical data and complementary explorations. RESULTS: We observed 3 groups. In group A (36% of the lesions), ADC mapping did not change image interpretation. This group was subdivided into 3 subgroups. A1: T2 and DIF weighted images are normal: no lesions and normal ACD map (n = 38 patients); A2: High intensity signal on T2 and low intensity signal on DIF: ischemic sequelae, ADC always increased (n = 32 lesions); A3: T2 normal and high intensity signal on DIF: hyper acute ischemia and ADC always decreased (n = 16 patients) In group B (high intensity signal on T2 and DIF, 54.5% of the lesions), ADC mapping changed the MRI interpretation: there was acute ischemia if the ADC was decreased (n = 113) and "pseudo-ischemic" lesions if the ADC was normal or increased (n = 17 patients). Group C was comprised of 23 lesions with a false negative ADC (9.5%). These lesions were always small recent ischemic lesions (< or = 5 mm) with a high intensity signal on DIF and a strictly normal ADC map. CONCLUSION: ADC mapping was found to be useful in 54.5% of the lesions and should not be considered as solely a research tool but also as a useful tool for routine clinical practice.

Adult↗