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Structural information in neuronal tissue as revealed by q-space diffusion NMR spectroscopy of metabolites in bovine optic nerve.

1H NMR diffusion experiments performed on the signal of the metabolites in bovine optic nerve showed that the signal decay due to diffusion is bi-exponential with a slow and a fast diffusing component. Diffusion was measured as a function of the diffusion time, and the data were analyzed as a function of b and q values. Bi-exponential fit was used to analyze the data, and the results were compared with the displacement distribution profiles obtained from the q-space analysis of the data. This q-space analysis showed that the fast diffusing component has a broad displacement distribution and appears not to be restricted. On the other hand, the slow diffusing component appears to be highly restricted to milieu in the order of 1-2 microm. The orientation of the sample with respect to the axis for which diffusion was measured affected mainly the relative sizes of the populations of each component, but had only a small effect on the extracted apparent diffusion coefficients. These results from both the b and the q value analyses suggest that the slow diffusing component is related to restricted diffusion of these metabolites in the axonal fibers, while the fast diffusing component represents diffusion of metabolites in cells and along the long axis of the nerve fibers. It is concluded that q-space analysis of metabolite diffusion enables extraction of structural information about the sample, and that the diffusion of the metabolites in optic nerve is dictated mainly by the cellular medium and microstructure of the tissue.

Animals↗

Diffusion-weighted MR imaging of intracerebral masses: comparison with conventional MR imaging and histologic findings.

BACKGROUND AND PURPOSE: The purposes of this study were to find the role of diffusion-weighted MR imaging in characterizing intracerebral masses and to find a correlation, if any, between the different parameters of diffusion-weighted imaging and histologic analysis of tumors. The usefulness of diffusion-weighted imaging and apparent diffusion coefficient (ADC) maps in tumor delineation was evaluated. Contrast with white matter and ADC values for tumor components with available histology were also evaluated. METHODS: Twenty patients with clinical and routine MR imaging/CT evidence of intracerebral neoplasm were examined with routine MR imaging and echo-planar diffusion-weighted imaging. The routine MR imaging included at least the axial T2-weighted fast spin-echo and axial T1-weighted spin-echo sequences before and after contrast enhancement. The diffusion-weighted imaging included an echo-planar spin-echo sequence with three b values (0, 300, and 1200 s/mm(2)), sensitizing gradient in the z direction, and calculated ADC maps. The visual comparison of routine MR images with diffusion-weighted images for tumor delineation was performed as was the statistical analysis of quantitative diffusion-weighted imaging parameters with histologic evaluation. RESULTS: For tumors, the diffusion-weighted images and ADC maps of gliomas were less useful than the T2-weighted spin-echo and contrast-enhanced T1-weighted spin-echo images in definition of tumor boundaries. Additionally, in six cases of gliomas, neither T2-weighted spin-echo nor diffusion-weighted images were able to show a boundary between tumor and edema, which was present on contrast-enhanced T1-weighted and/or perfusion echo-planar images. The ADC values of solid gliomas, metastases, and meningioma were in the same range. In two cases of lymphomas, there was a good contrast with white matter, with strongly reduced ADC values. For infection, the highest contrast on diffusion-weighted images and lowest ADC values were observed in association with inflammatory granuloma and abscess. CONCLUSION: Contrary to the findings of previous studies, we found no clear advantage of diffusion-weighted echo-planar imaging in the evaluation of tumor extension. The contrast between gliomas, metastases, meningioma, and white matter was generally lower on diffusion-weighted images and ADC maps compared with conventional MR imaging. Unlike gliomas, the two cases of lymphomas showed hyperintense signal on diffusion-weighted images whereas the case of cerebral abscess showed the highest contrast on diffusion-weighted images with very low ADC values. Further study is required to find out whether this may be useful in the differentiation of gliomas and metastasis from lymphoma and abscess.

Adult↗

Large disparity between gallium and antimony self-diffusion in gallium antimonide.

The most fundamental mass transport process in solids is self-diffusion. The motion of host-lattice ('self-') atoms in solids is mediated by point defects such as vacancies or interstitial atoms, whose formation and migration enthalpies determine the kinetics of this thermally activated process. Self-diffusion studies also contribute to the understanding of the diffusion of impurities, and a quantitative understanding of self- and foreign-atom diffusion in semiconductors is central to the development of advanced electronic devices. In the past few years, self-diffusion studies have been performed successfully with isotopically controlled semiconductor heterostructures of germanium, silicon, gallium arsenide and gallium phosphide. Self-diffusion studies with isotopically controlled GaAs and GaP have been restricted to Ga self-diffusion, as only Ga has two stable isotopes, 69Ga and 71Ga. Here we report self-diffusion studies with an isotopically controlled multilayer structure of crystalline GaSb. Two stable isotopes exist for both Ga and Sb, allowing the simultaneous study of diffusion on both sublattices. Our experiments show that near the melting temperature, Ga diffuses more rapidly than Sb by over three orders of magnitude. This surprisingly large difference in atomic mobility requires a physical explanation going beyond standard diffusion models. Combining our data for Ga and Sb diffusion with related results for foreign-atom diffusion in GaSb (refs 8, 9), we conclude that the unusually slow Sb diffusion in GaSb is a consequence of reactions between defects on the Ga and Sb sublattices, which suppress the defects that are required for Sb diffusion.

Journal Article↗

MR imaging of high-grade cerebral gliomas: value of diffusion-weighted echoplanar pulse sequences.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of diffusion-weighted echoplanar MR imaging in the examination of high-grade brain gliomas compared with that of conventional spin-echo (SE) or fast spin-echo (FSE) MR imaging. We hypothesize that diffusion-weighted MR imaging may enable us to differentiate various tumor components on the basis of differences in the diffusion of water. SUBJECTS AND METHODS: Conventional SE and FSE MR images were obtained in 10 patients with high-grade brain glioma. Diffusion-weighted echoplanar MR images were obtained with a head gradient coil capable of providing diffusion-weighted imaging along the cephalocaudal axis. Using SE and FSE MR images as a baseline, we evaluated the diffusion-weighted MR images for usefulness in distinguishing tumor components on the basis of differences in diffusion. RESULTS: Areas of tumor that showed significant enhancement on T1-weighted SE MR images obtained after injection of contrast material were markedly hyperintense on diffusion-weighted images and had a lower apparent diffusion coefficient (ADC) than the ADCs for nonenhancing tumor and peritumoral edema. Cystic or necrotic portions of tumor showed the most signal suppression on diffusion-weighted images and were associated with the highest ADCs. On T2-weighted FSE MR images, areas of hyperintensity observed in white matter oriented parallel to the direction of the diffusion gradient could be differentiated into two patterns on the basis of findings on diffusion-weighted images: areas that showed marked signal suppression with a higher ADC, most likely representing areas of predominantly peritumoral edema, and areas that showed a lesser degree of signal suppression with similar but slightly lower ADCs than those of edema, most likely representing areas of predominantly nonenhancing tumor. CONCLUSION: Diffusion-weighted echoplanar MR imaging is a useful technique for examining high-grade cerebral gliomas. It enabled us to differentiate various components of the tumor (e.g., enhancing, nonenhancing, cystic, or necrotic) and to distinguish areas of predominantly nonenhancing tumor from areas of predominantly peritumoral edema when the abnormality was located in the white matter aligned in the direction of the diffusion-weighted gradient. Diffusion-weighted echoplanar MR imaging appears to be a powerful tool in the characterization of brain neoplasms.

Adolescent↗

Water diffusion in the different microenvironments of breast cancer.

The parameters that characterize the intricate water diffusion in tumors may serve to reveal their distinct pathology. Specifically, the application of diffusion magnetic resonance imaging (MRI) can aid in characterizing breast cancer, as well as monitoring response to therapy. We present here a non-invasive, quantitative MRI investigation, at high spatial resolution, of water diffusion in hormonal dependent MCF7 breast tumors implanted orthotopically in immunodeficient mice. Distinctive MRI protocols were designed in this study, utilizing a broad range of diffusion times and diffusion gradient strengths. Application of these protocols allowed water diffusion in the tissue extracellular and intracellular compartments to be distinguished, and the effect of restricted diffusion and water exchange on the water diffusion in these compartments to be evaluated. Pixel-by-pixel analysis yielded parametric maps of the estimated volume fraction and apparent diffusion coefficient of each compartment. The diffusion of the water in the extracellular microenvironment was approximately two fold slower than that of free water, and in the intracellular compartment was about one order of magnitude slower than that of free water and demonstrated restriction of water diffusion at long diffusion times. Mapping of the water fraction in each compartment was further employed to monitor changes during tumor progression and to assess tumor response to hormonal manipulation with a new antiestrogenic drug, tamoxifen methiodide (TMI). It was found that, in parallel to the growth arrest by this drug, the volume fraction of the slowly diffusing water increased, suggesting a TMI-induced cell swelling. This study can serve as a basis for extending diffusion breast MRI in the clinical setting.

Animals↗

Concentration dependence of the self-diffusion of human and Lumbricus terrestris hemoglobin.

The self-diffusion coefficient of the extracellular hemoglobin of Lumbricus terrestris (mol wt 3.7 x 10(6) daltons) has been measured at protein concentrations ranging from 2 to 25 g/100 ml. The self-diffusion coefficient of human hemoglobin has been measured at concentrations between 10 and 43 g/100 ml. For these measurements, (14)C-labeled hemoglobin was made to diffuse from one Millipore filter into three consecutively arranged Millipore filters containing unlabeled hemoglobin. After a suitable time the filters were separated, and the protein diffusion coefficient was determined from the distribution of radioactivity in the four filters with a table given by Kawalki (1894, Ann. Phys. Chem.52:166-190.). The following results were obtained. The diffusion coefficient of Lumbricus hemoglobin is 1.2 x 10(-7) cm(2)s(-1) at a protein concentration of 2.1 g/100 ml, and is reduced to about 1/10 of this value when the concentration is 25 g/100 ml (T = 21 degrees C). Between 0 and 16 g/100 ml the logarithm of the diffusion coefficient of Lumbricus hemoglobin falls linearly with concentration. Above 16 g/100 ml a marked increase in the concentration dependence of the diffusion coefficient is observed. Extrapolation of the data to zero hemoglobin concentration yields a limiting value of the diffusion coefficient of Lumbricus hemoglobin of 1.3 x 10(-7) cm(2)s(-1). The diffusion coefficient of human hemoglobin is 4.5 x 10(-7) cm(2)s(-1) at a hemoglobin concentration of 9.7 g/100 ml, and falls to 0.14 x 10(-7) cm(2)s(-1) at a hemoglobin concentration of 43.0 g/100 ml. In addition to diffusivities, the viscosities of human and Lumbricus hemoglobin solutions were measured in a wide range of protein concentrations.The concentration dependence of the diffusivity of Lumbricus hemoglobin is compared to that of myoglobin, ovalbumin, and tetrameric hemoglobin. Proportionality between the diffusion coefficient and the reciprocal of the viscosity of the protein solution is found for all these proteins. It is also shown that an equation proposed by Anderson (1973) gives an excellent description of the diffusivity of the various proteins up to moderate protein concentrations. Above concentrations of 16 g/100 ml for Lumbricus hemoglobin, and 30 g/100 ml for tetrameric hemoglobin, however, protein diffusivity falls much more rapidly with increasing concentration than is predicted by this equation.

Animals↗

Analysis of diffusion models for protein adsorption to porous anion-exchange adsorbent.

The ion-exchange adsorption kinetics of bovine serum albumin (BSA) and gamma-globulin to an anion exchanger, DEAE Spherodex M, has been studied by batch adsorption experiments. Various diffusion models, that is, pore diffusion, surface diffusion, homogeneous diffusion and parallel diffusion models, are analyzed for their suitabilities to depict the adsorption kinetics. Protein diffusivities are estimated by matching the models with the experimental data. The dependence of the diffusivities on initial protein concentration is observed and discussed. The adsorption isotherm of BSA is nearly rectangular, so there is little surface diffusion. As a result, the surface and homogeneous diffusion models do not fit to the kinetic data of BSA adsorption. The adsorption isotherm of gamma-globulin is less favorable, and the surface diffusion contributes greatly to the mass transport. Consequently, both the surface and homogeneous diffusion models fit to the kinetic data of gamma-globulin well. The adsorption kinetics of BSA and gamma-globulin can be very well fitted by parallel diffusion model, because the model reflects correctly the intraparticle mass transfer mechanism. In addition, for both the favorably bound proteins, the pore diffusion model fits the adsorption kinetics reasonably well. The results here indicate that the pore diffusion model can be used as a good approximate to depict protein adsorption kinetics for protein adsorption systems from rectangular to linear isotherms.

Adsorption↗

Diffusive uptake in passive and active adsorbent sampling using thermal desorption tubes.

Low flow active sampling techniques collecting vapors and gases using thermally desorbable adsorbents are now feasible and desirable in many applications as they permit long integration times, the potential for miniaturized sampling configurations, and other advantages. At very low air flow rates (< 1 ml min(-1)), diffusive uptake on adsorbents in conventional sorbent tubes may equal or exceed the active (pumped) uptake rate, and even at low flow rates (1-4 ml min(-1)), diffusive uptake may significantly bias measurements. Thus, corrections to account for the diffusive flux or means to limit the diffusive uptake are needed in low flow applications. This paper presents (1) a theoretical analysis of the role of diffusive and advective uptake for several sampling geometries of tube-type samplers; (2) experimental confirmation using both laboratory and field studies; (3) estimates of the tortuosity and porosity of the glass wool packing used to retain the adsorbent, parameters needed to estimate diffusive fluxes in passive and active sampling; (4) a demonstration that orifice-equipped low flow active samplers can reduce diffusive uptake and improve precision, and (5) a model predicting the saturated adsorbent layer that helps to account for the gradual decline in uptake rates seen in passive sampling. Diffusive uptake will depend on the tube configuration and diffusion coefficient of the substance of interest, but for conventional sampling tubes (0.4-0.5 cm id, 1.5 cm air gap), sample flow rates should be maintained above 1 to 4 ml min(-1) to keep errors below 5%. Laboratory experiments showed close agreement with theoretical calculations, and the field study using 1 to 4 d sampling periods and 0.3 ml min(-1) flows demonstrated that the orifice-equipped samplers essentially eliminated diffusive uptake. No significant practical difficulties are encountered using orifices, e.g., pressure drop is minimal. Experimental estimates of tortuosity (0.79 +/- 0.02) and porosity (0.92 +/- 0.10) of the glass wool packing (0.3 cm length) represent relatively little resistance to diffusion; however, variation in the packing and adsorbent placement can degrade the precision achievable by passive samplers. Diffusion barriers, consisting most simply of an orifice, may be used to lower the diffusive uptake. A needle-type orifice permits flows below 0.1 ml min(-1) and is suitable for sampling periods as long as several weeks, and it provided greater precision than conventional open-ended sampling tubes (8% compared to 13%). Finally, the gradual decrease in diffusive fluxes often seen in passive sampling is attributed to additional resistance posed by a saturated adsorbent layer, in agreement with a simple model based on total VOCs and specific adsorptivity of the adsorbent.

Adsorption↗

Diffusion-weighted MR imaging of global cerebral anoxia.

BACKGROUND AND PURPOSE: Diffuse cerebral anoxia is a devastating event, and its acute findings, as revealed by conventional MR imaging and CT scanning, may be subtle. We analyzed diffusion-weighted and conventional MR images of patients with diffuse cerebral anoxia to determine their usefulness in establishing the diagnosis during the acute period and in determining the age of insult. METHODS: We reviewed 11 MR imaging studies of 10 patients who had experienced prolonged cardiac arrest. All of the patients underwent echo-planar diffusion-weighted imaging with low- and high-strength B values and multiplanar unenhanced MR imaging. We considered bright areas on the high-strength diffusion-weighted images to be abnormal when compared with low-strength images. Special attention was given to the cortex, basal ganglia, thalami, hippocampi, cerebellum, and white matter. Conventional MR studies also were reviewed, and abnormalities noted. The medical records of all of the patients were reviewed. RESULTS: Four patients who underwent imaging during the acute period (<24 hours) had bright basal ganglia (n = 2), bright cerebellum (n = 3), and bright cortex (n = 1) shown on their diffusion-weighted images. For these patients, conventional MR images showed questionable increased T2-weighted signal intensity in the basal ganglia (n = 1), and the results of two studies were judged to be normal. During the early subacute period (24 hours-13 days), four patients were studied, and were determined to have an abnormal cortex (n = 3) and basal ganglia (n = 2). For two of these patients, conventional MR images showed similar abnormalities, and the results of one study were normal. For two patients who underwent imaging during the late subacute period (14-20 days), diffusion-weighted images showed abnormalities mostly confined to white matter. Two patients who underwent imaging during the chronic phase (>21 days) had normal results of their diffusion-weighted imaging and one had evidence of laminar necrosis revealed by conventional MR imaging. CONCLUSION: During the acute period, high-strength diffusion-weighted images showed the abnormal basal ganglia, cerebellum, and cortex to a better extent than did conventional MR images. During the early subacute period, gray matter abnormalities were seen on diffusion-weighted images. During the late subacute period, diffusion-weighted images showed mostly white matter abnormalities. During the chronic stage, the results of diffusion-weighted imaging were normal. Our findings suggest that diffusion-weighted images are helpful for evaluating and dating diffuse cerebral anoxia, and therefore aid in the determination of prognosis and management of these patients.

Adolescent↗

Self-diffusion of water in multicellular spheroids measured by magnetic resonance microimaging.

Nuclear magnetic resonance microimaging measurements of the self-diffusion coefficient of water in large (greater than 2 mm) EMT-6 multicellular spheroids were performed in order to elucidate diffusion mechanisms in tumors. Pulsed gradient spin echo-imaging methods were developed for measuring diffusion in an intravoxel multicompartment system. The self-diffusion coefficient (at 22 degrees C) for water in the medium (Dm) consisted of only a single diffusion compartment [Dm = 1.99 +/- 0.03 (SE) x 10(-5) cm2/s]. Similarly, the spheroid necrotic center showed a single water diffusion compartment with a self-diffusion coefficient (Dc) significantly lower than that of the medium (Dc = 1.54 +/- 0.05 x 10(-5) cm2/s). The spheroid viable rim region showed two distinct compartments of approximately equal volume, one with a large diffusion coefficient (1.70 +/- 0.12 x 10(-5) cm2/s) and a second with a significantly smaller diffusion coefficient (0.25 +/- 0.01 x 10(-5) cm2/s). We propose that these two experimentally distinguishable compartments correspond to the extra- and intracellular regions, respectively, of the viable rim of the spheroid. Although the diffusion coefficients were significantly different in the medium, the necrotic center, and the viable rim, the activation energy for diffusion was the same in the three regions (0.20 eV). Studies of perfused spheroids at 37 degrees C show the same dependence of the diffusion coefficients on the diffusion filter as observed for unperfused spheroids at 22 degrees C. These results demonstrate the ability of nuclear magnetic resonance microimaging to investigate diffusion at the cellular level, which will lead to a better understanding of microenvironmental regulation in tumors.

Animals↗

[Diffusion tensor analysis with nuclear magnetic resonance in human central nervous system].

Nuclear magnetic resonance has been used to measure the diffusivity of water molecules. In central nervous system, anisotropic diffusion, which is characterized by apparent diffusion tensor Dapp zeta, is thought to be related to neuronal fiber tract orientation. For precise observation of anisotropic diffusion, it is needed to determine the diagonal and off-diagonal elements of Dapp zeta. Once Dapp zeta is estimated from a series of diffusion weighted images, a tissue's orthotropic principal axes and diffusivity of each direction are determined from eigenvalues and eigenvectors of Dapp zeta. There are several methods to represent anisotropic diffusion with Dapp zeta. Examples are diffusion ellipsoids constructed in each voxel depicting both these principal axes and the mean diffusion length in these directions, trace invariant values and its mapping image, largest eigenvalue, and ratio of largest eigenvalue to the other eigenvalue. In this study, the author investigated practical procedure to analyze diffusion tensor Dapp zeta using both of spin-echo and echo-planer diffusion weighted imagings with 3-tesla magnetic resonance machine in human brain. The ellipsoid representation provided particularly useful information about microanatomy including neuronal fiber tract orientation and molecular mobility reflective of microstructure. Furthermore, in the lesion of Wallerian degeneration, the loss of anisotropy of local apparent diffusion was observed. It is suggested that the function of axons can be observed via degree of anisotropy of apparent diffusion. Consequently, diffusion tensor analysis is expected to be a powerful, noninvasive method capable of quantitative and functional evaluation of the central nervous system.

Adult↗

The effect of acid cleaning on a fine pore ceramic diffuser aeration system.

Fine pore ceramic diffuser aeration, a very competitive high efficiency system, is widely used in aerobic biological processes for providing dissolved oxygen and mixing. Concern has been registered regarding the maintenance of these systems and their susceptibility to diffuser fouling. Selected ceramic diffusers, removed from the Madison Metropolitan Sewage District (MMSD) Nine Springs Wastewater Treatment Plant, Wisconsin, U.S.A., were fractured and analyzed in an attempt to identify the elemental components of the internal foulants and to evaluate the effect of acid cleaning on diffuser performance. The fouling condition of diffusers were initially characterized by dynamic wet pressure (DWP) measurements. Microimages taken from the non acid-treated diffuser profile using scanning electronic microscopy revealed the structural difference of internal foulants which may correspond to the stage of foulant formation. For diffuser samples from the MMSD facility, calcium phosphate minerals were predominant foulants, although some calcium carbonate and organic carbon have also accumulated. The clogging of diffuser internal void space was verified by observing thin sections of diffuser cross-sections. Selected diffusers were then treated with strong acid to study its effectiveness in removing internal foulant by acid soaking. Even though the acid treated diffusers showed significant reduced DWP values, acid treatment, the common diffuser cleaning technique, does not completely remove these internal foulants. This may be the reason why the acid-treated diffusers never reached like-new conditions. Furthermore, once these acid-treated diffusers are installed back to the aeration tank, these dewatered foulant sections may very well behave as seed for future clogging.

Acids↗

Apparent diffusion coefficients and chemical species of neptunium (V) in compacted Na-montmorillonite.

Diffusion of neptunium (V) in compacted Na-montmorillonite was studied through the non-steady state diffusion method. In this study, two experimental attempts were carried out to understand the diffusion mechanism of neptunium. One was to establish the diffusion activation energy, which was then used to determine the diffusion process in the montmorillonite. The other was the measurement of the distribution of neptunium in the montmorillonite by a sequential batch extraction. The apparent diffusion coefficients of neptunium in the montmorillonite at a dry density of 1.0 Mg m-3 were from 3.7 x 10(-12) m2 s-1 at 288 K to 9.2 x 10(-12) m2 s-1 at 323 K. At a dry density of 1.6 Mg m-3, the apparent diffusion coefficients ranged between 1.5 x 10(-13) m2 s-1 at 288 K and 8.7 x 10(-13) m2 s-1 at 323 K. The activation energy for the diffusion of neptunium at a dry density of 1.0 Mg m-3 was 17.5 +/- 1.9 kJ mol-1. This value is similar to those reported for diffusion of other ions in free water, e.g., 18.4 and 17.4 kJ mol-1 for Na+ and Cl-, respectively. At a dry density of 1.6 Mg.m-3, the activation energy was 39.8 +/- 1.9 kJ mol-1. The change in the activation energy suggests that the diffusion process changes depending on the dry density of the compacted montmorillonite. A characteristic distribution profile was obtained by the sequential extraction procedure for neptunium diffused in compacted montmorillonite. The estimated fraction of neptunium in the pore water was between 3% and 11% at a dry density of 1.6 Mg m-3 and at a temperature of 313 K. The major fraction of the neptunium in the montmorillonite was identified as neptunyl ions sorbed on the outer surface of the montmorillonite. These findings suggested that the activation energy for diffusion and the distribution profile of the involved nuclides could become powerful parameters in understanding the diffusion mechanism.

Bentonite↗

Diffusion theory, the cell and the synapse.

The possibility exists that the cell internum is far more highly organised right down to the molecular level than was hitherto appreciated, to the point where ideas of a relatively solid-state chemistry model have been entertained (Coulson, R.A., 1993. The flow theory of enzyme kinetics--a role of solid geometry in the control reaction velocity in live animals. Int. J. Biochem. 25, 1445-1474). This contrasts sharply with the traditional dogma that diffusion is the mechanism by which molecules interact within an aqueous solution of the cell internum, although it should have been clear from an early stage that diffusion could not play other than a very restricted role in metabolic regulation. When physicists began to question certain aspects of the fundamental Law of Heat Conductance formulated over 170 years ago by Fourier, Diffusion Theory was also implicated (Maddox, J., 1989. Heat conductance is a can of worms. Nature 338, 373), and application of Fick's Laws of Diffusion to living systems criticised (Agutter P.S., Malone, P.C., Wheatley, D.N., 1995. Intracellular transport mechanisms: a critique of diffusion theory. J. Theoret. Biol. 176, 261-272). While we have argued (Wheatley, D.N., Malone, P.C., 1993. Heat conductance, diffusion theory and intracellular metabolic regulation. Biol. Cell 79, 1-5) that diffusion cannot be prevented from occurring, we found that, irrespective of whether it was a valid theory, diffusion was of little relevance in most actively metabolising cell systems. However, diffusion is still perceived as essential for interacting molecules to demonstrate their specificities. Any new model of the internal state of the living cell has to resolve this dilemma. The question also relates to molecular movement and ligand-receptor interactions outside the cell. In looking at this situation, attention was paid to one site in the body in which diffusion has long been assumed to be essential, namely in the passage of the chemical transmitter between one neurone and the next across the synaptic cleft. A detailed examination of this assumption has helped to identify one possible place in which the importance of diffusion over a distance of no more than 20-30 nm occurs, although objections to diffusion being involved have been raised. The outcome, however, only re-enforces the conviction that diffusion has little role in metabolic activity and is normally 'assisted' in almost all aspects of cell physiology.

Action Potentials↗

Perfusion, diffusion and their heterogeneities limiting blood-tissue O2 transfer in muscle.

The relative roles of blood flow (perfusion) and diffusion in O2 supply to exercising muscle can be estimated using a simple model consisting of an O2-consuming tissue block in contact with blood (perfusion Q, slope of O2 equilibirum curve beta) through a resistance to O2 diffusion (O2-diffusing capacity D). The decisive variable is the 'equilibration index' Y=D/(Qbeta). With decreasing Y, diffusion limitation increases and perfusion limitation decreases (Y > 3 indicates predominant perfusion limitation; 3 > Y > 0.1, combined perfusion and diffusion limitation, Y < 0.1, prevailing diffusion limitation). On the basis of literature data on humans at maximum O2 uptake, O2 supply to muscle is shown to be always limited by both perfusion and diffusion. In nomoxia, perfusion limitation is prevalent, but in hypoxia diffusion limitation becomes predominant. The underlying model assumes perfect homogeneity of muscles with respect to O2 requirement, diffusion conditions and blood flow. In numerous studies on isolated and in situ muscles a pronounced heterogeneity of blood flow has been found, also during exercise and at maximal O2 uptake. It is shown that with unequal distribution of blood flow and/or O2-diffusing capacity the efficiency of O2 transfer is reduced with reference to the homogeneous model. Therefore, the diffusing capacity value calculated on the basis of the homogeneous model is an underestimate of the true diffusing capacity and diffusion limitation is overestimated.

Diffusion↗

The role of cytochrome c diffusion in mitochondrial electron transport.

We have compared the modes and rates of cytochrome c diffusion to the rates of cytochrome c-mediated electron transport in isolated inner membranes and in whole intact mitochondria. For inner membranes, an increasing ionic strength results in an increasing rate of cytochrome c diffusion, a decreasing concentration (affinity) of cytochrome c near the membrane surface as well as near its redox partners, and an increasing rate of electron transport. For intact mitochondria, an increasing ionic strength results in a parallel, increasing rate of cytochrome c-mediated electron transport. In both inner membranes and intact mitochondria the rate of cytochrome c-mediated electron transport is highest at physiological ionic strength (100-150 mM), where the diffusion rate of cytochrome c is highest and its diffusion mode is three-dimensional. In intact mitochondria, succinate and duroquinol-driven reduction of endogenous cytochrome c is greater than 95% at all ionic strengths, indicating that cytochrome c functions as a common pool irrespective of its diffusion mode. Using a new treatment to obtain bimolecular diffusion-controlled collision frequencies in a heterogenous diffusion system, where cytochrome c diffuses laterally, pseudo-laterally, or three-dimensionally while its redox partners diffuse laterally, we determined a high degree of collision efficiency (turnover/collisions) for cytochrome c with its redox partners for all diffusion modes of cytochrome c. At physiological ionic strength, the rapid diffusion of cytochrome c in three dimensions and its low concentration (affinity) near the surface of the inner membrane mediate the highest rate of electron transport through maximum collision efficiencies. These data reveal that the diffusion rate and concentration of cytochrome c near the surface of the inner membrane are rate-limiting for maximal (uncoupled) electron transport activity, approaching diffusion control.

Animals↗

In-hospital outcome of percutaneous transluminal coronary angioplasty for long lesions and diffuse coronary artery disease.

We performed coronary angioplasty on 151 long or diffuse lesions (120 long and 31 diffuse) in 141 patients (86% male, mean age 50 +/- 9 years). Long lesions were defined as lesions 11-20 mm in length and diffuse lesions as lesions longer than 20 mm, or three or more lesions in the same vessel. One or more adverse morphologic features were present in 131 (93%) lesions. Long balloons were used in 44%, significantly more often for diffuse disease (long lesions 39% and diffuse disease 64%; P = 0.004). Newer devices including the rotational atherectomy device (9 lesions), stents and perfusion balloons were employed in 18 (12%) lesions, more often for diffuse lesions (long lesions 8% vs. diffuse lesions 26%; P = 0.017). Lesion severity was comparable in the two groups (long lesions: 88 +/- 7%; diffuse lesions: 88 +/- 8%), but diffuse lesions were associated with significantly higher residual stenosis (long lesions: 6 +/- 8%; diffuse lesions: 12 +/- 13%, P = 0.01). Major complications occurred in five (3.5%) patients, including one death (0.7% mortality). The angiographic and clinical success rates for all patients were 99% and 96%, respectively, and were comparable for long and diffuse lesions. Judicious case selection and the use of long balloons and newer interventional devices permit coronary angioplasty for long lesions and diffuse disease with excellent success and a low risk of complications. Diffuse lesions are associated with more frequent use of long balloons and newer devices, especially rotational atherectomy and slightly higher residual stenosis as compared to long lesions.

Adult↗

A high-resolution abrasive method for determining diffusion profiles of sorbing radionuclides in dense argillaceous rocks.

The diffusion of (134)Cs(+) and (22)Na(+) in Opalinus Clay (OPA) was studied by in-diffusion laboratory experiments. The diffusive tracer profiles in the rock were determined using a high-resolution abrasive peeling method. The radionuclide activities in the grinding swarf were measured directly via gamma-spectrometry. By choosing the appropriate abrasive paper, a resolution down to 15 microm can be achieved. This is important when analysing strongly sorbing radionuclides such as tri- and tetravalent actinides that show steep, shallow diffusion profiles. In this study, a resolution between 20 and 90 microm was obtained which was sufficient for a good spatial resolution of the diffusion profiles. Both the effective diffusion coefficients and the distribution coefficients of the radionuclides could be determined by applying a single reservoir with decreasing source concentration analysis for a semi-infinite case. In the case of (22)Na(+), effective diffusion coefficients of D(e)=2.0 x 10(-11)m(2)s(-1) and D(e)=1.5 x 10(-11)m(2)s(-1) for Benken (Zurcher Weinland) OPA and Mont Terri OPA, respectively, were derived. The distribution coefficients were K(d)=3.1 x 10(-4) and 0.9 x 10(-4)m(3)kg(-1), respectively. For (134)Cs(+) the effective diffusion coefficients were higher, i.e. D(e)=3.1 x 10(-11)m(2)s(-1) for OPA from Benken and D(e)=3.0 x 10(-11)m(2)s(-1) for OPA from Mont Terri. The distribution coefficients determined were K(d)=0.16 m(3)kg(-1) for Benken and 0.23 m(3)kg(-1) for Mont Terri. Comparison of the data obtained for the weakly sorbing (22)Na(+) with those from earlier through-diffusion experiments showed that there is good agreement between the two methods. In the case of (134)Cs(+) such a comparison was not possible because through-diffusion data are not available. Because through-diffusion methods cannot be applied to strongly sorbing tracers in reasonable time periods, in-diffusion combined with high-resolution abrasive peeling offers an excellent alternative for measuring the diffusion properties of strongly sorbing tracers in dense argillaceous rocks.

Journal Article↗