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PubMed2006

Time dependence of 3He diffusion in the human lung: measurement in the long-time regime using stimulated echoes.

A stimulated-echo-based technique was developed to measure the long-time-scale apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breath-hold acquisition. Computer simulations were used to evaluate the performance of the technique and guide the selection of appropriate parameter values for obtaining accurate ADC values. The technique was used in 10 healthy subjects and two subjects with chronic obstructive pulmonary disease (COPD) to measure the global ADC for diffusion times between a few tenths of a second and several seconds, and to acquire spatial maps of the ADC for a diffusion time of 1.5 s. The reproducibility of the technique and its sensitivity to the direction of diffusion sensitization were also investigated. In healthy subjects, global ADC values decreased by severalfold over the range of diffusion times measured (mean values = 0.039 and 0.023 cm2/s at diffusion times of 0.61 and 1.54 s, respectively). ADC maps were generally uniform, with mean values similar to the corresponding global values. For the two COPD subjects, global ADC values were substantially greater than those of every healthy subject at all diffusion times measured. In addition, regional elevations of ADC values were far more conspicuous on long-time-scale ADC maps than on short-time-scale ADC maps.

Adult↗

PubMedDate not supplied

Diffusion-weighted NMR imaging: application to experimental focal cerebral ischemia.

Changes in diffusion NMR imaging are believed to be based on intra/extracellular water homeostasis and will therefore reflect early disturbances of ion and water homeostasis after the onset of an ischemic event. Diffusion-weighted NMR imaging (DWI) thus has the potential to be a sensitive tool for the observation of stroke evolution. The present state of information extracted from diffusion-weighted NMR imaging for the understanding of cerebral focal ischemia in experimental research has been compiled in this review. The emphasis was set on three essential aspects of the technique in relation to focal ischemia. Firstly, the sensitivity of diffusion-weighted imaging for ischemic alterations is described. A comparison with conventional NMR imaging using relaxation time changes is included. Secondly, the comparison of the diffusion-weighted imaging with invasive techniques is discussed. Here, interpretation of the physiological, metabolic and hemodynamic alterations reflected in the observed diffusion changes is presented. The importance of regionally resolved information for a meaningful assignment of DWI changes to pathophysiological alterations is demonstrated for the differentiation between ischemic core and penumbra from DWI and quantitative diffusion coefficient data. The time dependence of correlations with physiological, biochemical and hemodynamic variables as a further important aspect is stressed. Thirdly, the potential of the technique for the assessment of development and effectiveness of new therapeutical strategies against stroke is demonstrated.

Animals↗

PubMed1996

Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI.

Quantitative-diffusion-tensor MRI consists of deriving and displaying parameters that resemble histological or physiological stains, i.e., that characterize intrinsic features of tissue microstructure and microdynamics. Specifically, these parameters are objective, and insensitive to the choice of laboratory coordinate system. Here, these two properties are used to derive intravoxel measures of diffusion isotropy and the degree of diffusion anisotropy, as well as intervoxel measures of structural similarity, and fiber-tract organization from the effective diffusion tensor, D, which is estimated in each voxel. First, D is decomposed into its isotropic and anisotropic parts, [D] I and D - [D] I, respectively (where [D] = Trace(D)/3 is the mean diffusivity, and I is the identity tensor). Then, the tensor (dot) product operator is used to generate a family of new rotationally and translationally invariant quantities. Finally, maps of these quantitative parameters are produced from high-resolution diffusion tensor images (in which D is estimated in each voxel from a series of 2D-FT spin-echo diffusion-weighted images) in living cat brain. Due to the high inherent sensitivity of these parameters to changes in tissue architecture (i.e., macromolecular, cellular, tissue, and organ structure) and in its physiologic state, their potential applications include monitoring structural changes in development, aging, and disease.

Animals↗

PubMed2002

Directionality of stripes formed by anisotropic reaction-diffusion models.

Turing mechanism explains the formation of striped patterns in a uniform field in which two substances interact locally and diffuse randomly. In a twin paper, to explain the directionality of stripes on fish skin in closely related species, we studied the effect of anisotropic diffusion of the two substances on the direction of stripes, in the cases in which both substances have high diffusivity in the same direction. In this paper, we study the direction of stripes in more general situations in which the diffusive direction may differ between the two substances. We derive a formula for the direction of stripes, based on a heuristic argument of unstable modes of deviation from the uniform steady state. We confirm the accuracy of the formula by computer simulations. When the diffusive direction is different between two substances, the directions of stripes in the spatial pattern change smoothly with the magnitude of anisotropy of two substances. When the diffusive direction of the two substances is the same, the stripes are formed either parallel or perpendicular to the common diffusive direction, depending on the relative magnitude of the anisotropy. The transition between these two phases occurs sharply.

Animals↗

PubMed2001

Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture.

This study investigates water diffusion changes in Wallerian degeneration. We measured indices derived from the diffusion tensor (DT) and T2-weighted signal intensities in the descending motor pathways of patients with small chronic lacunar infarcts of the posterior limb of the internal capsule on one side. We compared these measurements in the healthy and lesioned sides at different levels in the brainstem caudal to the primary lesion. We found that secondary white matter degeneration is revealed by a large reduction in diffusion anisotropy only in regions where fibers are arranged in isolated bundles of parallel fibers, such as in the cerebral peduncle. In regions where the degenerated pathway crosses other tracts, such as in the rostral pons, paradoxically there is almost no change in diffusion anisotropy, but a significant change in the measured orientation of fibers. The trace of the diffusion tensor is moderately increased in all affected regions. This allows one to differentiate secondary and primary fiber loss where the increase in trace is considerably higher. We show that DT-MRI is more sensitive than T2-weighted MRI in detecting Wallerian degeneration. Significant diffusion abnormalities are observed over the entire trajectory of the affected pathway in each patient. This finding suggests that mapping degenerated pathways noninvasively with DT-MRI is feasible. However, the interpretation of water diffusion data is complex and requires a priori information about anatomy and architecture of the pathway under investigation. In particular, our study shows that in regions where fibers cross, existing DT-MRI-based fiber tractography algorithms may lead to erroneous conclusion about brain connectivity.

Aged↗

PubMed1997

A tutorial on the diffusibility and reactivity of free nitric oxide.

In this review, I consider the quantitative consequences of the diffusion of free NO in determining its biological actions. Several studies have measured the extent to which NO diffuses away from an NO-producing cell, and the distance of its diffusion is quite large, on the order of 100-200 microm. This wide diffusibility is consistent also with the high value for its diffusion constant, 3300 microm2/s. Mathematical simulations based on this wide diffusibility suggest that, within spatial limits of approximately 0.3-0.4 mm, the actions of free NO are dictated by the total number of NO-producing cells within this location as opposed to where the NO-producing cells are located within this space. These results suggest that the actions of NO are surprisingly long range and the diffusion of NO is an important determinant of its biological actions. Thus, the effects of NO on individual target cells may be determined more by each cell's preprogrammed characteristic response to NO than by proximity to an NO source. In addition, scavenging of NO by hemoglobin in blood vessels should represent a significant sink for its scavenging, posing difficulty for the postulate that only free NO functions as EDRF.

Animals↗

PubMed2005

The anomalous Einstein-Stokes behaviour of oxygen and other low molecular weight diffusants.

Almost a century ago, Einstein and Sutherland independently derived equations that describe the relationship between diffusion of solutes and the molecular parameters of those solutes. In that time it has been recognized that, although the equations adequately describe the diffusion of large and medium-sized molecules, there is deviation from this relationship for small molecules. Many authors have attempted to redefine the equations for diffusion, with varying degrees of success, but generally have not attempted to consider the fundamental events that may be occurring at the molecular level during the diffusion of small molecules. In this presentation, we attempt to provide such an explanation, particularly with respect to the diffusion of oxygen through water. We consider the possibility of a random rotational model that complements the (slower) translational process of traditional diffusion and thereby provides accelerated diffusion of small molecules. It is hoped that our description of this model may provide a basis for the development of mathematical modelling of the process.

Diffusion↗

PubMed1990

Brain water accumulation in pseudotumour cerebri demonstrated by MR-imaging of brain water self-diffusion.

We studied brain water self diffusion in pseudotumour cerebri by MR-imaging using single spin echo pulse sequences with pulsed magnetic field gradients of different magnitude. The methods is based on the fact that the movement of water molecules is restricted in brain tissue and that accumulation of water in the brain tissue will enhance the self diffusion of water. In order to evaluate the brain water content in pseudotumour cerebri we compared the water self diffusion coefficient in various regions of the brain in pseudotumour patients with that of healthy controls. Ten patients with pseudotumour cerebri were studied. All had increased ICP and increased resistance to CSF outflow. All patients had normal conventional MR spin echo images without focal lesions and a normal sized ventricular system. All patients had abnormal diffusion images showing increased water diffusion. Some patients had in particular increased diffusion in the periventricular regions, others in the whole brain. The diffusion coefficients in all brain regions of interest were significantly higher in patients than in controls. The findings suggest that patients with pseudotumour cerebri have a convective transependymal flow of water causing an interstitial brain oedema and in addition an intracellular brain water accumulation.

Adult↗

PubMed1994

Diffusion anisotropy of cerebral ischaemia.

Focal cerebral ischemia was produced by occlusion of the middle cerebral artery with a silicone cylinder in Wistar rats. Diffusion-weighted echo-planar images (DW-EPIs) using the motion-probing gradient (MPG) method were acquired at 1-3 hours and 24-48 hours after occlusion. Apparent diffusion coefficients (ADCs) were calculated from these images in ischemic lesions and in normal unoccluded regions. Results were as follows. 1. Ischemic lesions could be detected on the DW-EPIs at 1 hour after occlusion. 2. The ADC of water in the brain tissue was smaller than that of free water as a result of restricted diffusion. 3. Anisotropic diffusion that probably can be attributed to the myelin sheath was observed in the normal deep white matter. 4. In the ischemic lesions, the ADC decreased rapidly within 1-3 hours after occlusion and then slightly further declined after 24-48 hours. In the ischemic deep white matter, diffusion anisotropy disappeared at 24-48 hours after occlusion. Diffusion-weighted imaging may have applications in the examination of pathophysiological mechanisms in cerebral ischemia by means of evaluation of ADC and diffusion anisotropy.

Animals↗

PubMed1990

Capillarity and diffusion distances in skeletal muscles in birds.

Tissue capillarity and diffusion distances were determined for red and white skeletal muscles of adult birds ranging in mass from 10.8 to 6200 g. In addition, literature values for capillarity and diffusion distances in skeletal muscles of mammals were incorporated into the data set. Muscle mass was closely coupled to body mass. However, no significant allometric relations were found for any of the other variables measured. Number of capillaries per fiber was not correlated with cross sectional area of individual muscle fibers. Thus, capillary density decreased in a hyperbolic manner against fiber area and diffusion distance decreased in a hyperbolic manner against the number of capillaries per muscle fiber. Red muscles had significantly higher numbers of capillaries per fiber and significantly shorter diffusion distances than did white muscles. The patterns for tissue capillarity and diffusion distances in avian muscle reported here are similar to values reported previously for mammalian muscles. In both taxonomic groups capillarity and diffusion distances are independent of body mass. In addition, diffusion distances are characteristic of capillaries distributed in random arrays through the muscle cross section.

Animals↗

PubMed1987

Rapid lateral diffusion of lectin-labelled glycoconjugates in the human colonic adenocarcinoma cell line HT29. Comparison with the synthetic lipid analogue diI-C14.

The lateral diffusion of lectin-labelled glycoconjugates was studied in the human colon carcinoma cell line HT29 using fluorescence photobleaching techniques. HT29 cells were grown in either Dulbecco's modified Eagle's medium with glucose (25 mM; DMEM-Glu) or with galactose (25 mM; DMEM-Gal). Cell cultivation in the DMEM-Gal medium was assumed to promote a transformation of the cells to become small-intestinal-like with characteristic microvilli and associated enzymes. The diffusion of glycoconjugates labelled with fluoresceinated Triticum vulgaris agglutinin (Wheat germ agglutinin; WGA), Ricinus communis agglutinin-I (RCA-I), Concanavalia ensiformis agglutinin (ConA), Ulex europaeus agglutinin-I (UEA-I) and Arachis hypogaea agglutinin (PNA) was in all cases rapid, with a diffusion constant (D) ranging between 0.4 and 0.8 X 10(-8) cm2 s-1. As a comparison the diffusion of the fluorescent synthetic lipid analog diI-C14 was characterized by D = 0.8 - 1.0 X 10(-8) cm2 s-1. The diffusion of lectin-labelled surface components could not be related to the presence of microvilli on HT29 cells grown in DMEM-Gal, which ought to yield an apparently lower diffusion rate. The results indicate either that surface glycoconjugates in HT29 cells are dominated by glycolipid, or that the labelled glycoproteins are more or less free to diffuse in the plane of the membrane.

Adenocarcinoma↗

PubMed1977

Oxygen diffusivity in tumor tissue (DS-carcinosarcoma) under temperature conditions within the range of 20--40 degrees C.

The O2 diffusion constants D and K of tumor tissue (DS-Carcinosarcoma in the rat kidney) were determined at temperatures of 20, 30, 37, and 40 degrees C. The following mean values were obtained for the conditions of 37 degrees C: D = 1.75-10(-5) cm2/s and K = 1.9-10(-5) mlO2/cm-min-atm. Within the range of 20-40 degrees C, temperature variations in tumor tissue cause changes in the O2 diffusion coefficient D of 2.0-2.5%/C and in the Krogh O2 diffusion constant K of 0.5-1.5%/C. The measured O2 diffusion constants for tumor tissue correspond to values of normal tissue with similar water content. This indicates that the insufficient O2 supply in DS-Carcinosarcoma is due not to unfavorable O2 diffusivity of the tumor tissue but rather to a decreased convective O2 transport and to insufficient capillarization. An analysis of O2 diffusion in DS-Carcinosarcoma tissue using the determined O2 diffusion constants lead to the result that, under the conditions of arterial normoxia and normocapnia, critical O2 supply conditions are to be expected when the intercapillary distance exceeds approximately 120 micrometer.

Animals↗

PubMed1992

Diffusion of contrast media in cerebrospinal fluid: comparison of iohexol, iopamidol and iotrolan in vitro.

Diffusion of iohexol (300 and 240 mgI/ml), iopamidol (300 and 200 mgI/ml), and iotrolan (300 and 240 mgI/ml) in the cerebrospinal fluid (CSF) of 16 patients was studied in vitro. Test tubes containing CSF were kept in a waterbath at 37 degrees C. Contrast medium was injected along the wall into the tubes, and diffusion of contrast media in the tubes was followed with repeated computed tomography for 5 h. The contents of the tubes were then mixed by shaking, and the tubes were scanned immediately and 8 h later. The contrast media first settled in the bottom of the tubes and then diffused upwards. Iotrolan diffused more slowly than the other media, but the difference was only significant at a concentration of 300 mgI/ml. The difference between iohexol and iopamidol was minimal. In general, diffusion was slower in CSF samples with an elevated protein content, but the difference in the diffusion of contrast medium in normal and pathological CSF was seldom statistically significant, perhaps owing to the small number of samples (5) with an elevated protein content. All contrast medium-CSF mixtures remained homogeneous after mixing. These experiments showed measurable differences in the diffusion of contrast media in CSF, but it does not seem very likely that these would be significant in clinical practice.

Cerebrospinal Fluid Proteins↗

PubMed1981

Studies of diffusion in calvaria.

The rates of diffusion of small ions and neutral molecules through isolated calvaria have been determined. Compared with data published on self-diffusion and diffusion through cartilage, H2O, 3-O-methylglucose, lactate, sulfate, and methylamine diffuse at approximately 2/3 the expected rate. Diffusion of H2O and sulfate was unaffected by the administration of the diphosphonate 1-hydroxyethane-1,1-diphosphonate (EHDP), although phosphate fluxes are markedly diminished. Diffusion of water was nearly doubled by vitamin D deficiency. A 1-week treatment with 1,25(OH)2D3 had no effect on H2O diffusion while returning calcium influx to normal. It is concluded that bone matrix permits a flow of small neutral and ionized molecules nearly comparable to that in cartilage. When changes in calcium and phosphate influx are observed, they can be ascribed to the exchange properties of bone mineral and not to changes in matrix permeability.

3-O-Methylglucose↗

PubMedDate not supplied

Diffusion and transfer of antibody proteins from a sugar-based hydrogel.

Diffusion of antibody protein from hydrogel films and hydrogel encapsulated in a microcapillary was studied. Thin hydrogel films were formed by crosslinking 6-acryloyl-B-O-methylgalactoside with N,N'-methylene-bis-acrylamide and the diffusive transport of monoclonal antimouse IgG-FITC into and out of the hydrate films was measured. Diffusion coefficients in 2 and 4% crosslinked hydrogel films were measured. The measured diffusion constants determined for IgG in both the 2 and 4% hydrogel films were comparable to the free diffusion of IgG in bulk water (Dmean approximately 10(-7) cm2/s). In addition, 2% crosslinked hydrogels were prepared in a capillary tube and the transport of antimouse IgG-FITC into and out of the hydrated hydrogel was measured. Kinetic analysis indicated that the protein transport through the capillary hydrogel was faster than would be expected for a simple diffusion process. Finally, by utilizing the diffusion of antibody from the capillary hydrogel, transfer of antibody to a silica surface was demonstrated. A capillary hydrogel loaded with antimouse IgG-FITC was used to transfer the protein to a silica surface forming a 30-micron spot of antibody, which was imaged using fluorescence microscopy. These results may lead to the development of a nonlithographic method of patterning antibodies on surfaces for use in integrated microimmunosensors.

Acrylamides↗

PubMed1999

Effect of hyaluronidase on albumin diffusion in lung interstitium.

Albumin diffusion measured in an isolated segment of rabbit lung interstitium with a radioactive tracer ((125)I-albumin) technique was independent of albumin concentration and similar to the free diffusion of albumin in water (Qiu et al, 1998. J Appl Physiol 85: 575-583). We studied the effect of hyaluronidase on the diffusion of albumin. Isolated rabbit lungs were inflated with silicon rubber by way of airways and blood vessels, and two chambers were bonded to the sides of a approximately 0.5-cm thick slab enclosing a vessel with an interstitial cuff. One chamber was filled with 2 g/dl albumin solution containing (125)I-albumin and 0.02 g/dl hyaluronidase. Unbound (125)I was removed from the tracer by dialysis before use. The other chamber filled with Ringer's solution was placed within a NaI(Tl) scintillation detector. Diffusion of tracer was measured continuously for 120 h. Albumin diffusion coefficient (D) and interstitial area (A) were obtained by fitting the tracer-time curve with the theoretical solution of the equation describing one-dimension diffusion of a solute across a membrane. D averaged 5.2 x 10(-7) cm(2)/s for albumin diffusion with hyaluronidase, 20% less than that measured previously without hyaluronidase. Hyaluronidase had no effect on A. Results indicated an interaction between albumin and interstitial hyaluronan that was the opposite of the steric effect on albumin excluded volume measured in solution.

Animals↗

PubMed2001

[Diffusion weighted MRI: ischemic and traumatic injuries of the central nervous system].

Diffusion weighted magnetic resonance imaging (DWI) represents a recent development that extends imaging from the depiction of the neuroanatomy into the field of functional and physiologic processes. DWI measures a fundamentally different physiologic parameter than conventional MRI. Image contrast is related to differences in the microscopic motion (diffusion) of water molecules within brain tissue rather than a change in total tissue water. Consequently, DWI can reveal pathology where conventional T1- and T2-weighted MR images are negative. DWI has clinically proven its value in the assessment of acute cerebral stroke and trauma by showing cerebral injury early due to ist ability to discriminate between lesions with cytotoxic edema (decreased diffusion) from lesions with vasogenic edema (increased diffusion). Full tensor DWI allows to calculate a variety of functional maps, the most widely used maps include maps of apparent diffusion coefficients and isotropic diffusion. In addition maps of anisotropic diffusion can be calculated which are believed to give information about the integrity and location of fiber tracts. This functional-anatomical information will most probably play an increasingly important role in the early detection of primary and secondary tissue injury from various reasons and could guide and validate current and future neuroprotective treatments.

Animals↗

PubMed2000

Diffusion of small solutes in the lateral intercellular spaces of MDCK cell epithelium grown on permeable supports.

The diffusion coefficients of four solutes ranging in molecular weight from 238 to 10,000 in the lateral intercellular spaces (LIS) of cultured kidney cells (MDCK) grown on permeable supports were determined from the spread of fluorescence produced after the release of caged compounds by a pulse from a UV laser. Two types of experiments were performed: measurement of the rate of change of fluorescence after releasing a caged fluorophore, and measurement of the change in fluorescence of a relatively static fluorescent dye produced by the diffusion of an uncaged ligand for the dye. Fluorescence intensity was determined by photon-counting the outputs of a multichannel photomultiplier tube. Diffusion coefficients were determined in free solution as well as in the LIS of MDCK cells grown on permeable supports and the hindrance factor, theta, determined from the ratio of the free solution diffusivity to that in the LIS. The hindrance factors for 3000-MW dextran, 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS, MW 524) and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES, MW 238) were not significantly different from 1. The diffusion of 10,000-MW dextran was substantially reduced in the LIS with a theta of 5.6 +/- 0.3. Enzymatic digestion by neuraminidase of the sialic acid residues of the glycosylation groups in the LIS increased the diffusivity of the 10,000-MW dextran 1.8-fold indicating hindrance by the glycocalyx. We conclude that small solutes, such as Na(+) and Cl(-), would not be significantly restricted in their diffusion in the LIS and that solute concentration gradients could not develop along the LIS under physiologic conditions.

Animals↗