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Noninvasive monitoring of cerebral oxygenation during vasomotor reactivity tests by a new near-infrared spectroscopy device.

BACKGROUND: Spatially resolved spectroscopy is a recently developed technique for noninvasive monitoring of cerebral tissue oxygenation using the photon diffusion theory. METHODS: We studied this technique with a new, commercial near-infrared spectroscopy (NIRS) device during vasomotor reactivity tests in 28 healthy volunteers (mean age 31.0 years; SD 10.6 years) and compared it with values assessed by the modified Beer-Lambert law and indices from simultaneous transcranial Doppler sonography of both middle cerebral arteries. We measured O(2) reactivity as percentage change of cerebral blood flow velocity (CBFV), as absolute change in the concentrations (measured in micromol/l) of oxygenated (HbO(2)), deoxygenated (Hb) and total hemoglobin (HbT), and as change in the tissue oxygenation index (TOI) during inhalation of 100% oxygen. CO(2) reactivity was calculated as percentage change of CBFV (NCR), as absolute change in the concentrations of HbO(2), Hb, and HbT (micromol/l), and as change in TOI (%) per 1% increase in end-tidal CO(2). RESULTS: One hundred percent oxygen inhalation lead to a decrease in CBFV (mean +/- SD: left -8.0 +/- 7.0%, p = 0.000; right -9.6 +/- 7.6%, p = 0.000), an increase in HbO(2) (0.99 +/- 1.07 micromol/l), Hbdiff (2.23 +/- 1.72 micromol/l), and TOI (3.1 +/- 1.5%), and a decrease in Hb (-1.22 +/- 0.74 micromol/l), significant from baseline values (p = 0.0000). CO(2) reactivity was: NCR left 25.4 +/- 14.7%; NCR right 25.9 +/- 13.4%; HbO(2) 1.99 +/- 0.97 micromol/l; Hb -1.24 +/- 0.81 micromol/l; HbT 0.81 +/- 1.0 micromol/l, and TOI 3.7 +/- 2.2%. O(2) reactivity in TCD did not correlate with NIRS reactivities (Pearson p > 0.05), but NCR did correlate with changes in HbO(2), Hb, and TOI (Pearson p < 0.01). TOI was closely related to indices derived from the Beer-Lambert law (Pearson p < 0.03), but not with mean arterial blood pressure or skin blood flow during vasomotor reactivity tests. CONCLUSION: Spatially resolved spectroscopy provides an encouraging, noninvasive new tool to study cerebral tissue oxygenation during vasomotor reactivity tests consistent with physiological changes.

Adult↗

Multi-wavelength time domain optical mammography.

A time-resolved optical mammograph operating at 7 wavelengths (637, 683, 785, 832, 905, 916, and 975 nm) in compressed breast geometry was developed. Its clinical application was started on patients bearing malignant and benign lesions. Late gated intensity images are used to obtain information on the spatial distribution of the absorption properties of breast. Scattering images derived from the diffusion theory are also applied for lesion detection and characterization. Cancers are identified in intensity images at short wavelengths, due to the high blood content, while cysts are typically characterized by low scattering at all wavelengths. The increase (from 4 to 7) in the number of wavelengths as compared to the previous versions of the instrument aims at improving the robustness of the fitting procedures for a better estimate of tissue composition and structure and of physiological parameters. Moreover, the new wavelengths contribute to the qualitatively identify tissue composition from intensity images, and could assist lesion detection.

Breast Neoplasms↗

Total RNA concentration as an index of microbial activity and oxygen supply in an oxidation ditch.

Total RNA and chromosomal DNA concentrations at a municipal wastewater treatment plant with an oxidation ditch (OD) were monitored for 1.5 years using commercial extraction kits for DNA and RNA. No parameters correlated with the chromosomal DNA concentration. The total RNA concentration exhibited better correlation than the solids retention time and the mixed liquor suspended solids with the removal rate of total organic carbon, and can be regarded as an index of microbial activity. The total RNA concentration varied with a cycle of one year and increased at lower water temperatures in this OD. When diffusion theory was taken into account, it was found that the oxygen dissolution rate increased at lower temperature, and a small change in the oxygen dissolution rate caused a large variation in microbial activity and also affected nitrification and denitrification. The information was insufficient to clarify the various reaction relationships, but total RNA concentration will likely be useful as an index of microbial activity in actual wastewater treatment reactors.

Bacteria, Aerobic↗

Boundary conditions for the diffusion equation in radiative transfer.

Using the method of images, we examine the three boundary conditions commonly applied to the surface of a semi-infinite turbid medium. We find that the image-charge configurations of the partial-current and extrapolated-boundary conditions have the same dipole and quadrupole moments and that the two corresponding solutions to the diffusion equation are approximately equal. In the application of diffusion theory to frequency-domain photon-migration (FDPM) data, these two approaches yield values for the scattering and absorption coefficients that are equal to within 3%. Moreover, the two boundary conditions can be combined to yield a remarkably simple, accurate, and computationally fast method for extracting values for optical parameters from FDPM data. FDPM data were taken both at the surface and deep inside tissue phantoms, and the difference in data between the two geometries is striking. If one analyzes the surface data without accounting for the boundary, values deduced for the optical coefficients are in error by 50% or more. As expected, when aluminum foil was placed on the surface of a tissue phantom, phase and modulation data were closer to the results for an infinite-medium geometry. Raising the reflectivity of a tissue surface can, in principle, eliminate the effect of the boundary. However, we find that phase and modulation data are highly sensitive to the reflectivity in the range of 80-100%, and a minimum value of 98% is needed to mimic an infinite-medium geometry reliably. We conclude that noninvasive measurements of optically thick tissue require a rigorous treatment of the tissue boundary, and we suggest a unified partial-current--extrapolated boundary approach.

Light↗

Lateral photon transport in dense scattering and weakly absorbing media of finite thickness: asymptotic analysis of the space-time Green function.

The asymptotic law for the radial distribution of radiance density from an isotropic point source placed in a slab of homogeneous absorbing and scattering material is obtained within the framework of diffusion theory. The exponential shape of the tail of the resulting Green function has been observed but was not theoretically explained until now. We derive formulas for both the steady-state and the time-dependent problems. The theoretical results are verified by comparison with Monte Carlo simulations.

Computer Simulation↗

Generalized diffusion solution for light scattering from anisotropic sources.

The traditional diffusion theory, often used for isotropic sources, becomes inaccurate at short source-detector spacings and cannot be applied to media with large absorption or with small scattering strengths. We show that for any type of source anisotropy, a Green's-function-based procedure can remove these limitations. The accuracy of the new approach is examined through a comparison with the numerical solution to the radiative transfer equation.

Journal Article↗

How old is the most recent ancestor of two copies of an allele?

An important clue to the evolutionary history of an allele is the structure of the neighboring region of the genome, which we term the genomic background of the allele. Consider two copies of the allele. How similar we expect their genomic background to be is strongly influenced by the age of their most recent common ancestor (MRCA). We apply diffusion theory, first used by Motoo Kimura as a tool for predicting the changes in allele frequencies over time and developed by him in many articles in this journal, to prove a variety of new results on the age of the MRCA under the simplest demographic assumptions. In particular, we show that the expected age of the MRCA of two copies of an allele with population frequency f is just 2Nf generations, where N is the effective population size. Our results are a first step in running exact coalescent simulations, where we also simulate the history of the population frequency of an allele.

Alleles↗

Soft sweeps: molecular population genetics of adaptation from standing genetic variation.

A population can adapt to a rapid environmental change or habitat expansion in two ways. It may adapt either through new beneficial mutations that subsequently sweep through the population or by using alleles from the standing genetic variation. We use diffusion theory to calculate the probabilities for selective adaptations and find a large increase in the fixation probability for weak substitutions, if alleles originate from the standing genetic variation. We then determine the parameter regions where each scenario-standing variation vs. new mutations-is more likely. Adaptations from the standing genetic variation are favored if either the selective advantage is weak or the selection coefficient and the mutation rate are both high. Finally, we analyze the probability of "soft sweeps," where multiple copies of the selected allele contribute to a substitution, and discuss the consequences for the footprint of selection on linked neutral variation. We find that soft sweeps with weaker selective footprints are likely under both scenarios if the mutation rate and/or the selection coefficient is high.

Adaptation, Physiological↗

Optical properties of human prostate at 732 nm measured in mediated photodynamic therapy.

Characterization of the tissue light penetration in prostate photodynamic therapy (PDT) is important to plan the arrangement and weighting of light sources so that sufficient light fluence is delivered to the treatment volume. The optical properties (absorption [mu(a)], transport scattering [mu(s)'] and effective attenuation [mu(eff)] coefficients) of 13 patients with locally recurrent prostate cancer were measured in situ using interstitial isotropic detectors. Measurements were made at 732 nm before and after motexafin lutetium (MLu)-mediated PDT in four quadrants. Optical properties were derived by applying the diffusion theory to the fluence rates measured at several distances (0.5-5 cm) from a point source. mu(a) and mu(s)' varied between 0.07 and 1.62 cm(-1) (mean 0.37 +/- 0.24 cm(-1)) and 1.1 and 44 cm(-1) (mean 14 +/- 11 cm(-1)), respectively. mu(a) was proportional to the concentration of MLu measured by an ex vivo fluorescence assay. We have observed, on average, a reduction of the MLu concentration after PDT, presumably due to the PDT consumption of MLu. mu(eff) varied between 0.91 and 6.7 cm(-1) (mean 2.9 +/- 0.7 cm(-1)), corresponding to an optical penetration depth (delta = 1/micro(eff)) of 0.1-1.1 cm (mean 0.4 +/- 0.1 cm). The mean penetration depth at 732 nm in human prostate is at least two times smaller than that found in normal canine prostates, which can be explained by a four times increase of the mean value of mu(s)' in human prostates. The mean light fluence rate per unit source strength at 0.5 cm from a point source was 1.5 +/- 1.1 cm(-2), excluding situations when bleeding occurs. The total number of measurements was N = 121 for all mean quantities listed above. This study showed significant inter- and intraprostatic differences in the optical properties, suggesting that a real-time dosimetry measurement and feedback system for monitoring light fluences during treatment should be considered for future PDT studies.

Humans↗

Changes in in vivo optical properties and light distributions in normal canine prostate during photodynamic therapy.

The optical absorption and transport scattering coefficients of normal prostate tissue have been measured in vivo in dogs. The measurements were made at 630 nm before and during treatment by Photofin photodynamic therapy using interstitial optical fiber fluence-rate detectors. Corresponding measurements were made ex vivo, at 1 week after treatment, in the contralateral lobe. The optical properties were derived by applying a diffusion theory model to the fluence rates measured at two different source-detector fiber distances. While the in vivo pretreatment and in vivo contralateral post-treatment absorption and scattering values are self-consistent and in agreement with published data, significant changes were observed in the light fluence rates, and hence in the derived optical properties, during light irradiation. The possible causes of such changes are considered, and the implications for light dosimetry in photodynamic therapy are discussed.

Animals↗

On transport of suspended particulates in tube flow.

Blood cells suspended in shear flows exhibit much larger dispersive motions than those predicted by the Stokes-Einstein formula for Brownian diffusion. The lateral migration and the erratic motions of the 8 microns red blood cells (RBC) is thought to be analogous to a diffusive process. It is shown that the often cited convective-diffusion theory may not be an adequate model for describing the transverse migration of suspended cells in blood flow. A comprehensive review of both the classical theory and of contemporary work in particle transport is presented, with particular emphasis on low Reynolds number tube flows. The mechanisms of Taylor dispersion, the effects of Brownian perturbations on translational and rotational motions of the suspended particles in shear fields, and the influence of integratable and chaotic advections, are individually examined. The classical experiment by Segre and Silberberg (1962) lead us to believe that particle hydrodynamics may play an important role in transverse migrations. In this light, we have further examined the hydrodynamic aspects of the so-called "tubular pinch" effect, the lateral migration of rigid spheres. We have also discussed the transverse motions of liquid drops, and the reversibility of the organization of suspensions in transport. The convective accelerations in the entrance region of a tube can produce relative velocities between fluid medium and various type of particulates if there is a difference in density. The deformable RBC, an "active-type" particle, can provide feedback to the flow from both mass and momentum considerations; the more rigid platelet, a "passive-type" particle, will experience a much smaller relative velocity as compared to the RBC. We may expect that particles of different densities are transported to different equilibrium annular positions before entering the fully developed flow region. The erratic, lateral movement of suspended particulates in steady laminar tube flow can be described by the usual Lagrangian coordinates.

Biological Transport↗

[Adsorption in stratum corneum and percutaneous penetration of propranolol hydrochloride].

The sorption and rate of permeation of propranolol hydrochloride were measured as a function of drug concentration in the solution bathing rat skin in vitro. The sorption isotherm was nonlinear, and can be expressed in Langmuir form. The lag time and apparent permeability coefficient through intact skin decreased as the concentration of donor compartment increased, and those through stripped skin were not varied. These results indicate that an adsorption process existed when propranolol hydrochloride penetrated through the stratum corneum. Based on the adsorption--diffusion theory, a mathematical formula was developed for expressing the relationship between the concentration of drug and permeability coefficient through the skin quantitatively.

Animals↗

Role of plasma viscosity in platelet adhesion.

Platelet adhesion to the vessel wall is initiated by transport of blood platelets from the bulk flow to the wall. The process of diffusion and convection of the platelets is affected by rheological conditions such as well shear rate, red blood cell (RBC) deformability, and viscosity of the medium. To study the effect of plasma viscosity on platelet adhesion, perfusion experiments with a rectangular perfusion chamber were performed. Reconstituted blood, consisting of washed platelets and washed RBCs, was circulated through this chamber for 5 minutes at a wall shear rate of 300 s-1. Different albumin concentrations were made, to obtain different medium viscosities (0.89 to 1.85 mPa.s). Platelet adhesion decreased with increasing medium viscosity up to viscosities of 0.95 mPa.s, but increased with medium viscosity above this value. Instead of human albumin solution, different plasma viscosities were obtained by dilution of Waldenström plasma with buffer. Plasma was depleted of fibronectin, which gave a final plasma viscosity of 2.0 mPa.s, and was dialyzed against HEPES buffer and subsequently diluted with the dialysis buffer in different fractions (0.89 to 2.00 mPa.s). Perfusions were performed over a purified von Willebrand factor coating on glass, or over an endothelial cell matrix, preincubated with von Willebrand factor. With both surfaces, platelet adhesion was dependent on the plasma viscosity in a similar way: at low plasma viscosities, adhesion was decreased with increasing plasma viscosity, while at higher plasma viscosities, adhesion increased with plasma viscosity. Adhesion values at higher plasma viscosity or at higher human albumin concentrations could be explained by effects of the medium on the rigidity of the RBCs, since platelet adhesion is known to be increased by enhanced RBC rigidity. Effects of the medium on the deformability of the RBCs were measured separately with the laser diffraction method. These experiments confirmed that presence of human albumin or plasma in the measuring suspension increased the rigidity of RBCs. To prevent influence of the medium on the RBCs in perfusion experiments, the RBCs were fixated with glutaraldehyde. Perfusion experiments with fixated RBCs in plasma over a von Willebrand factor preincubated endothelial cell matrix, showed a consequent decrease in adhesion with increasing plasma viscosity, according to the diffusion theories, whereas the increase of adhesion at high plasma viscosities was lacking. This suggests that the latter effect was entirely due to increased transport of platelets by more rigid RBCs.

Blood Viscosity↗

[Non-invasive detection of the boundary of early breast tumor using DSF-DOT].

Traditional biomedical imaging technology has a difficulty in detecting the boundary of a breast tumor at its early stage since the difference in the sound resistance or density between the early breast tumor and normal tissue is small. In this paper, the boundary of an early breast tumor is detected successfully by using a new method called DSF-DOT (delta sound field diffusion optical tomography), which is based on a sound field and the light diffusion theory. At the same time, the influence of the size of the acting area of the sound field on the reconstruction of the tumor boundary is investigated in details. The work is useful for further research on the diagnosis of early breast cancers.

Breast Neoplasms↗

The state of water in living systems: from the liquid to the jellyfish.

The status of water in living systems is reviewed both from philosophical and scientific viewpoints. Starting from antique Mediterranean civilizations (Sumerian, Egyptian, Hebrew, Greek), a world trip is proposed through Norse myths, Siberian Shamanism, Hinduism, Taoism, Buddhism, Shinto, Mayan, Aztec, Inca, Aboriginal and African philosophies in order to convince that all humans share the same qualitative idea that water was a pre-requisite for life apparition. The quantitative aspect of the problem is further analyzed at the light of the scientific contributions from two leading scientists: R.A. Gortner and E.T. Jaynes. With Gortner's work it is demonstrated using the concrete example of the Jellyfish submitted at a Faraday discussion held in London in 1930, how a paradigm shift has occurred in the thirties concerning the status of bound water in the living cell. With Jaynes' work, the disastrous consequences of the entrenchment of diffusion theory in biology are critically examined and the exact meaning of the second law of thermodynamics for biological systems is given using the concrete example of muscle contraction. In conclusion, the importance of distinguishing between an ontological and epistemological level of knowledge is stressed and suggestions for reconciling scientific and philosophical approaches are given.

Animals↗

Barriers to prescribing the Copper T 380A intrauterine device by physicians.

From a questionnaire sent to all obstetricians and gynecologists and all family and general practitioners in San Diego County, California, regarding the Copper T 380A intrauterine device, substantial barriers to prescribing it were identified. Of all physicians responding, 40% reported that they were not recommending the Copper T 380A to anyone, the single most common reason given being concern about medical liability. A lack of knowledge about the new device, a lack of intrauterine device insertion skills, and certain medical practice settings were also important barriers to prescribing it. The new intrauterine device is considered in the context of innovation-diffusion theory. Substantial amounts of education and training and improvement in the medical-legal climate are needed before current barriers to prescribing the new device are removed.

Attitude of Health Personnel↗

Porin channels in intact cells of Escherichia coli are not affected by Donnan potentials across the outer membrane.

Donnan potential (interior negative) across the outer membrane of Escherichia coli was measured by the distribution of [14C]choline in a mutant with a deletion through the genes for the active transport of choline. Calculation showed that the presence of membrane-derived oligosaccharides in the periplasm could quantitatively explain the magnitude of the Donnan potential and the periplasmic volume. By measuring the permeability of porin channels in intact cells suspended in solutions of widely different ionic strengths, it was shown that changing Donnan potential from 5 mV to approximately 100 mV had no effect on the permeability of either OmpF or OmpC porin channel toward a zwitterionic compound, cephaloridine. Thus, the "voltage-dependent gating" of porin channel, previously reported from another laboratory, is likely to be an artifact of in vitro reconstitution. The influx of negatively charged compounds, however, was affected by the Donnan potential as expected from the electrolyte diffusion theory.

Algorithms↗