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PubMed2003

Measurement of fractional anisotropy using diffusion tensor MRI in supratentorial astrocytic tumors.

In vivo, water diffusion displays directionality due to presence of complex microstructural barriers in tissue. The extent of directionality of water diffusion can be expressed as a fractional anisotropy (FA) value, using diffusion tensor MR imaging (DTI). The aim of this study was to determine whether FA values indicate microstructures in astrocytic tumors. We performed DTI in 31 patients with astrocytic tumor, and measured the FA values of tumor and normal brain regions prior to CT-guided stereotactic biopsy. After biopsy, FA values were compared to assess the cellularity and vascularity of tumor tissue. Although mean FA values trended to differ among histological types, all mean tumor FA values were lower than those of normal brain regions. Positive correlation was observed between FA values and both cellularity (r = 0.65, p < 0.05) and vascularity (r = 0.45, p < 0.05). We had hypothesized that the FA value of an astrocytic tumor would be determined by a balance between factors increasing the directionality of water diffusion, such as high cellularity and/or vascularity, and factors decreasing the directionality of water diffusion, such as fiber destruction. However, our results suggest that the FA values of glioblastoma, anaplastic astrocytoma, diffuse astrocytoma and pilocytic astrocytoma are largely affected by cellularity and/or vascularity, whereas that of gliomatosis cerebri are largely affected by the preservation of nerve fibers. Measurement of FA value using DTI will allow prediction of histological characteristics such as cellularity, vascularity and/or fiber structure in astrocytic tumors.

Adult↗

PubMed2000

Oxygen diffusive barriers of rat distal colon: role of subepithelial tissue, mucosa, and mucus gel layer.

The contributions of subepithelial tissue, mucosa, and mucus gel layer as restraints for oxygen diffusion in rat distal colon in vitro were assessed by comparing oxygen transfer through preparations of isolated submucosa, isolated mucosa with and without the superficial mucus gel layer, and mucosa-submucosa mounted as flat sheets in a diffusion chamber. One side of the chamber was gassed with 95% O2-5% CO2 while the time course of oxygen concentration rise was measured in the continuously stirred opposite side, initially equilibrated with near-zero oxygen solution. The procedure does not affect epithelial viability. Diffusion in isolated mucosa was the same before and after KCN (5 mM) treatment, suggesting that epithelial oxygen consumption does not influence transfer rates. Subepithelial tissue, mucosa, and mucus gel layer are roughly responsible, respectively, for 12%, 56%, and 32% of oxygen diffusive hindrance. Diffusion coefficients range from 13% (mucosa-submucosa) to 54% (isolated submucosa) of that of water. Subepithelial tissue accounts for about 12% of total diffusive restraint.

Animals↗

PubMed2002

Diffusion-weighted magnetic resonance imaging in early stage of 5-fluorouracil-induced leukoencephalopathy.

We report a case of 5-fluorouracil (5-FU)-induced leukoencephalopathy in which magnetic resonance imaging (MRI) of the brain, including diffusion-weighted imaging (DWI), was performed serially. The initial T2-weighted and FLAIR images showed diffuse mild hyperintensity in bilateral deep cerebral white matter and corpus callosum, which on T1WI appeared as non-enhanced faint hypointensity. Isotropic DWI disclosed the abnormality as well-conspicuous diffuse hyperintensity with decreased ADC. Serial studies revealed that majority of the abnormal signal intensity on these sequences resolved, and the decreased ADC values approached normal. Some hyperintensity remained in the deep cerebral white matter and the splenium, but no further significant ADC change after normalization was noted. Measurement of ADC along the three orthogonal directions showed the presence of directional dependence of diffusion throughout the length of study. These findings suggest that early stage of 5-FU-induced leukoencephalopathy is associated with reversible restricted diffusion and preservation of anisotropy. Diffusion-weighted imaging may be useful for the diagnosis.

Adult↗

PubMed2002

Diffusion studies of VOC mixtures in a building material.

Volatile organic compound (VOC) adsorption by indoor materials will reduce peak concentrations, and subsequent desorption will prolong the presence of a compound indoors. Diffusion within materials plays an important role in this context. The purpose of this paper is to present two experimental set-ups to study VOC diffusion, and to show corresponding experimental results. The Field and Laboratory Emission Cell (FLEC) is in both cases an integral part of the set-up. The mass flow of VOC mixtures across gypsum board is studied. Diffusion of less polar VOCs in gypsum board can be fast (diffusion coefficients of 0.001-0.003 m2/h). Diffusion coefficients of chlorinated compounds are correlated with boiling points and molecular areas. Different compounds show similar diffusion properties.

Adsorption↗

PubMed2002

Measurement of diffusion coefficients of VOCs for building materials: review and development of a calculation procedure.

The measurement and prediction of building material emission rates have been the subject of intensive research over the past decade, resulting in the development of advanced sensory and chemical analysis measurement techniques as well as the development of analytical and numerical models. One of the important input parameters for these models is the diffusion coefficient. Several experimental techniques have been applied to estimate the diffusion coefficient. An extensive literature review of the techniques used to measure this coefficient was carried out, for building materials exposed to volatile organic compounds (VOC). This paper reviews these techniques; it also analyses the results and discusses the possible causes of difference in the reported data. It was noted that the discrepancy between the different results was mainly because of the assumptions made in and the techniques used to analyze the data. For a given technique, the results show that there can be a difference of up to 700% in the reported data. Moreover, the paper proposes what is referred to as the mass exchanger method, to calculate diffusion coefficients considering both diffusion and convection. The results obtained by this mass exchanger method were compared with those obtained by the existing method considering only diffusion. It was demonstrated that, for porous materials, the convection resistance could not be ignored when compared with the diffusion resistance.

Air Pollution, Indoor↗

PubMed1994

Extracellular volume fraction and diffusion characteristics during progressive ischemia and terminal anoxia in the spinal cord of the rat.

Extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda), and nonspecific uptake (k'), three parameters affecting the diffusion of substances in nervous tissue, were studied during ischemia and anoxia in the rat spinal cord gray matter in vivo. Progressive ischemia evoked by exsanguination, as well as anoxia evoked by respiratory or cardiac arrest, produced prominent extracellular K+ and pH changes closely related to a decrease in blood pressure and amplitude of field potentials. With use of ion-selective microelectrodes, the changes in the diffusion parameters were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA+) applied by iontophoresis concomitantly with ionic shifts. Under normoxic conditions (in rats with blood pressure of 80-110 mm Hg) diffusion parameters in the dorsal horn gray matter at depth 500-900 microns were as follows: alpha = 0.20 +/- 0.019, lambda = 1.62 +/- 0.12, k' = 4.6 +/- 2.5 x 10(-3) s-1 (mean +/- SD, n = 39). Extracellular K+, pH, and diffusion properties gradually changed during progressive ischemia. As the blood pressure fell to 50-60 mm Hg and field potential amplitude to 20-60%, K+ rose to 6-12 mM, pHe fell by approximately 0.05-0.1 pH unit, and volume fraction of the ECS significantly decreased, to alpha = 0.16 +/- 0.019 (n = 22). Even though the tortuosity remained virtually constant, the nonspecific uptake significantly decreased to k' = 3.4 +/- 1.8 x 10(-3) s-1. As the blood pressure fell to 20-30 mm Hg and field potential amplitude to 0-6%, K+ rose to 60-70 mM, pHe fell by approximately 0.6-0.8 pH unit, and all three diffusion parameters significantly changed. The ECS volume fraction decreased to alpha = 0.05 +/- 0.021, tortuosity increased to lambda = 2.00 +/- 0.24, and TMA+ uptake decreased to k' = 1.5 +/- 1.6 x 10(-3) s-1 (n = 12). No further increase in extracellular K+ or changes in the alpha were found during and up to 120 min after the death of the animal. However, there was a further significant increase in lambda = 2.20 +/- 0.14 and decrease in k' = 0.4 +/- 0.3 x 10(-3) s-1 (n = 24). The acid shift reached its maximum level at approximately 5-10 min after respiratory arrest and then the pHe gradually increased by approximately 0.2 unit. Full recovery to "normoxic" diffusion parameters was achieved after reinjection of the blood or after an injection of noradrenaline during severe ischemia, if this resulted in a rise in blood pressure above 80 mm Hg and a decrease in extracellular K+ below 12 mM.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2003

Accumulation of anchored proteins forms membrane diffusion barriers during neuronal polarization.

The formation and maintenance of polarized distributions of membrane proteins in the cell membrane are key to the function of polarized cells. In polarized neurons, various membrane proteins are localized to the somatodendritic domain or the axon. Neurons control polarized delivery of membrane proteins to each domain, and in addition, they must also block diffusional mixing of proteins between these domains. However, the presence of a diffusion barrier in the cell membrane of the axonal initial segment (IS), which separates these two domains, has been controversial: it is difficult to conceive barrier mechanisms by which an even diffusion of phospholipids could be blocked. Here, by observing the dynamics of individual phospholipid molecules in the plasma membrane of developing hippocampal neurons in culture, we found that their diffusion was blocked in the IS membrane. We also found that the diffusion barrier is formed in neurons 7-10 days after birth through the accumulation of various transmembrane proteins that are anchored to the dense actin-based membrane skeleton meshes being formed under the IS membrane. We conclude that various membrane proteins anchored to the dense membrane skeleton function as rows of pickets, which even stop the overall diffusion of phospholipids, and may represent a universal mechanism for formation of diffusion barriers in the cell membrane.

Actin Cytoskeleton↗

PubMed1999

Primary diffuse large B cell lymphoma of the stomach: analysis of somatic mutations in the rearranged immunoglobulin heavy chain variable genes indicates antigen selection.

Gastric low grade MALT lymphomas show a pattern of somatic mutations in their rearranged immunoglobulin genes, indicative of antigen selection. This provides evidence for antigen stimulation in the lymphomagenesis. Gastric diffuse large B cell lymphomas develop secondary to low grade MALT lymphoma or de novo. To study whether antigen-selection is also a feature of primary diffuse large B cell lymphomas, we analysed somatic mutations in the rearranged immunoglobulin heavy chain (IgH) variable genes (VH). The rearranged VH genes of six cases of gastric primary diffuse large B cell lymphoma were amplified from genomic or complementary DNA by a VH gene family-specific polymerase chain reaction method. The PCR products were directly sequenced and were compared to published germline sequences to analyse somatic mutations. Similarly to low grade MALT lymphomas 5/6 primary diffuse large B cell lymphomas show a pattern of somatic mutation in their rearranged VH genes, indicative of antigen selection and suggesting a role for antigens in lymphomagenesis. One case showed bi-allelic VH gene rearrangements, which were non-functional due to extensive deletions. Antigen selection could not be demonstrated or excluded. Antigen selection is a common feature in most analysed primary diffuse large B cell lymphomas, although some heterogeneity in the mechanisms involved in the lymphomagenesis of gastric primary diffuse large B cell lymphomas has not been excluded entirely (case 4).

Aged↗

PubMed2005

Measurements of diffusion coefficients in 1-D micro- and nanochannels using shear-driven flows.

The present paper describes a method for measuring the molecular diffusion coefficient of fluorescent molecules in microfluidic systems. The proposed static shear-driven flow method allows one to perform diffusion measurements in a fast and accurate manner. The method also allows one to work in very thin (i.e. submicron) channels, hence allowing the investigation of diffusion in highly confined spaces. In the deepest investigated channels, the obtained results were comparable to the existing literature values, but when the channel size dropped below the micrometer range, a significant decrease (more than 30%) in molecular diffusivity was observed. The reduction of the diffusivity was most significant for the largest considered molecules (ssDNA oligomers with a size ranging between 25 to 100 bases), but the decrease was also observed for smaller tracer molecules (FITC). This decrease can be attributed to the interactions of the analyte molecules with the channel walls, which can no longer be neglected when the depth of the channel reaches a critical value. The change in diffusivity seems to become more explicit as the molecular weight of the analytes increases.

DNA, Single-Stranded↗

PubMed2006

Diffusion in binary gas mixtures studied by NMR of hyperpolarized gases and molecular dynamics simulations.

The dependence of the individual mean square displacement of rare gases in binary mixtures is studied by a combined experimental and theoretical approach. We show that the diffusion constant can be varied in a considerable range by changing the molar fractions of the mixtures. On the experimental side, NMR diffusion measurements are done on hyperpolarized 3He and 129Xe, mixed with several inert buffer gases, in the presence of a magnetic field gradient. The results are compared to diffusion coefficients obtained from atomistic molecular dynamics simulations based on Lennard-Jones type potentials of the corresponding gas mixtures, and to appropriate analytical expressions, yielding very good mutual agreement. This study is the first quantitative validation of the effects of the mutual interactions between gas particles on the individual diffusion properties. It is shown that the dependency of gas phase diffusion properties on the local chemical environment may not be neglected, e.g. in diffusion-controlled chemical reactions.

Complex Mixtures↗

PubMed1991

Fatty-acid-binding protein facilitates the diffusion of oleate in a model cytosol system.

The proposed function of fatty-acid-binding proteins in facilitating the diffusion of their ligand has been examined in a cytosolic model using a steady-state diaphragm cell apparatus. The white muscle of ocean pout (Macrozoarces americanus) does not have a fatty-acid-binding protein: nor does it exhibit detectable beta-oxidative capacity, and as such is a good source of cytosol preparation. After determining the diffusion coefficient of oleate in this medium, fatty-acid-binding protein, isolated from the ventricle of this animal, was added and the apparent diffusion coefficient was again determined. The presence of the fatty-acid-binding protein increased the apparent diffusion coefficient of this long-chain fatty acid about 6-fold, from 0.087 x 10(-5) cm2.s-1 to 0.58 x 10(-5)cm2.s-1. This confirms the facilitated diffusion hypothesis as one role of fatty-acid-binding protein. The diffusion coefficients of oleate in 50 mM-sodium phosphate buffer, pH 7.4, at 10 degrees C and 25 degrees C (0.15 x 10(-5) cm2.s-1 and 0.28 x 10(-5) cm2.s-1 respectively) were also measured.

Animals↗

PubMed2003

Interprotein interactions are responsible for the confined diffusion of a G-protein-coupled receptor at the cell surface.

The monitoring of the movements of membrane proteins (or lipids) by single-particle tracking enables one to obtain reliable insights into the complex dynamic organization of the plasma membrane constituents. Using this technique, we investigated the diffusional behaviour of a G-protein-coupled receptor. The trajectories of the receptors revealed a diffusion mode combining a short-term rapid confined diffusion with a long-term slow diffusion. A detailed statistical analysis shows that the receptors have a diffusion confined to a domain which itself diffuses, the confinement being due to long-range attractive inter-protein interactions. The existing models of the dynamic organization of the cell membrane cannot explain our results. We propose a theoretical Brownian model of interacting proteins that is consistent with the experimental observations and accounts for the variations found as a function of the domain size of the short-term and long-term diffusion coefficients.

Animals↗

PubMed1986

Diffusion of butyrate through pig colonic mucus in vitro.

Using a modified equilibrium dialysis cell the rate of diffusion of butyrate through pig colonic mucus has been compared with that through other gels and unstirred layers. Relative diffusion coefficients were calculated for each layer. Layers of 8% polyacrylamide, and of caecal, mid-colonic and terminal colonic mucus, had coefficients that were 50-60% of the apparent free diffusion coefficient for butyrate, determined using layers made up of Millipore filters alone. The apparent free diffusion coefficients for butyrate (layers of agarose or filters) were 70% of previously determined values in the literature. This discrepancy can be explained by elements of the experimental procedure. All mucus layers differed significantly from layers of 2% agarose and Millipore filters but were not significantly different from layers of 8% polyacrylamide or from each other. Diffusion coefficients for butyrate in the mucus samples correlated with water content and carbohydrate content but had no relationship to protein content. The rate of diffusion of butyrate in colonic mucus layers was significantly reduced when compared with unstirred layers (P less than 0.05). Whether this has an effect on the butyrate supply to colonocytes in vitro and whether mucus in colonic disease behaves differently are subjects for further investigation.

Animals↗

PubMed2001

Diffusion theory and drug use.

This paper examines the applicability of the diffusion model to drug use. A variety of studies that employ the diffusion model to examine drug-related behaviour, including the use of alcohol, tobacco and illicit drugs, are discussed. Studies include those that focus on "natural" or spontaneous diffusion and those in which diffusion of a drug or a drug-related intervention is planned. Most studies examined support the application of the diffusion model in the study of drug use. The model is particularly valuable when new substances are introduced to a population or subgroup. The addition of economic and other forms of availability as a determinant of adoption would increase the power of the model. Recommended directions for research are outlined. The diffusion model has been used successfully in the study of drug use for several decades. More rigorous designs would strengthen this type of research and provide direction for policymakers and those involved in public health and education.

Diffusion of Innovation↗

PubMed1998

Water diffusion characteristics of human stratum corneum at different anatomical sites in vivo.

Despite its heterogeneity, stratum corneum (SC) has been described as a homogeneous membrane for water diffusion. We measured water flux across the SC, transepidermal water loss (TEWL), in six women, in vivo. At four anatomical sites--back, abdomen, forearm, and thigh--we took measurements during sequential tape stripping. The inverse of TEWL (1/TEWL) and removed SC thickness yielded a highly linear correlation (Pearson's r ranging between 0.88 and 0.99). Applying Fick's law of diffusion, we calculated SC thickness (H), and SC water diffusion coefficient (D). Comparing the results, SC of all women was significantly thicker (p < 0.05) at the extremities (12.7 +/- 4.2 microm, mean +/- SD, n = 12) than the abdomen (7.7 +/- 1.8 microm, n = 6). The calculated diffusion coefficient approximated 2.16 +/- 1.14x10(-9) cm2/s. Compared with the diffusion constant found for SC depleted of lipids, our value was 100-fold lower. In agreement with previous findings that intercellular lipids are a rate determining component of the SC barrier, we suggest that water diffuses mainly through the intercellular space. The calculation of H and/or D, however, is based on several variables: SC density, the water concentration difference, and the partition coefficient of water between viable epidermis and SC. The literature values vary widely. It is desirable to determine these parameters more precisely, especially if discrete differences, such as between anatomical sites, are to be revealed.

Abdomen↗

PubMed2003

Diffusion-weighted MRI in severe neonatal hypoxic ischaemia: the white cerebrum.

Presently, prognosis of infants with perinatal hypoxia-ischaemia is estimated using the Sarnat scale, which combines clinical evaluation and electroencephalography, in combination with magnetic resonance imaging (MRI) and or evoked potentials. While the value of conventional MRI is limited during the first week of life, diffusion-weighted MRI demonstrates effects of acute cerebral ischaemia within hours of onset. However, the exact value of diffusion MRI in the prognosis of infants with hypoxia-ischaemia has to be established in larger follow-up studies. In this report we describe 5 term (post-conceptional age 40 1/7 to 41 2/7 week) neonates with severe hypoxia-ischaemia and a characteristic pattern of diffusion changes. T 1 -weighted images showed a hyperintense cortical signal in only one case and extensive hyperintensity in the basal nuclei in all 5 cases. T 2 -weighted images showed nearly complete loss of cortical delineation in three cases. Increased signal on diffusion-weighted images was seen throughout all cortical and subcortical areas while the cerebellum remained normal. This pattern, which we refer to as the "white cerebrum", is most readily apparent on coronal images. The apparent diffusion coefficient (ADC) was calculated and compared to that of four control infants. In the cortex ADC values were lowered (0.70 +/- 0.17 micro m 2/msec [mean +/- standard deviation (SD)]; controls [n = 4]: 1.18 +/- 0.02 micro m 2/msec) as compared to values of ADC in the cerebellum (1.31 +/- 0.06 micro m 2/msec [mean +/- SD]; controls [n = 4]: 1.25 +/- 0.06 micro m 2/msec). All infants died in the perinatal period. In summary, the "white cerebrum" on diffusion-weighted MRI indicates severe neonatal hypoxia-ischaemia and is the counterpart of the white cerebellum on CT.

Diffusion Magnetic Resonance Imaging↗

PubMed2003

[Normal and abnormal water diffusion in the brain].

Diffusion magnetic resonance imaging (MRI) has become an important tool in the radiologic diagnosis of diseases of the brain as it measures molecular motion of water that characterizes the microstructure of tissues. Its most important clinical use to date is the early detection of cerebral ischemia by revealing the ischemic injury shortly after vessel occlusion and simultaneously providing therapy-relevant information on the tissue at risk. Furthermore, diffusion MRI is diagnostically promising in other diseases of the brain and is thus increasingly becoming part of routine clinical protocols in the diagnosis of tumors, inflammation, trauma, demyelination, dysmyelination and neurodegeneration. Although abnormalities of diffusion are generally not pathognomonic, diffusion MRI affords information about tissue changes for specific disorders that complements information obtained with standard MR techniques and frequently shows pathology earlier. In addition, diffusion MRI can be applied to plan, guide and follow-up biopsies or resective surgery. Particularly diffusion tensor imaging (DTI), which displays the orientation of white matter fibers, holds promise for improved surgical planning. Moreover, DTI can be used to detect changes in connectivity between functional brain areas. Therefore, DTI is highly relevant not only in advancing the knowledge of white matter diseases but also in stimulating research on normal brain development and brain aging.

Blood-Brain Barrier↗

PubMed1984

The diffusing capacity as a predictor of arterial oxygen desaturation during exercise in patients with chronic obstructive pulmonary disease.

We evaluated 48 patients with chronic obstructive pulmonary disease by means of pulmonary-function and exercise testing to determine whether any tests of pulmonary function could predict the development of arterial desaturation during exercise. We found that only two indexes--diffusing capacity and forced expiratory volume in one second (FEV1)--were predictive of desaturation. The diffusing capacity was more specific and sensitive than FEV1. A diffusing capacity above 55 per cent of predicted was 100 per cent specific in excluding desaturation, as compared with an 82 per cent specificity for an FEV1 above 55 per cent of predicted. With this cutoff point, the sensitivity of the diffusing capacity was 68 per cent, as compared with 46 per cent for the FEV1. Both the frequency and the magnitude of arterial desaturation increased substantially when the diffusing capacity was below 55 per cent of predicted. Testing the diffusing capacity should be useful in identifying which patients with chronic obstructive lung disease are likely to become desaturated during exercise and may therefore benefit from oxygen therapy.

Aged↗