Diffusion Weighting by the Trace of the Diffusion Tensor within a Single Scan

The anisotropy of the water diffusion tensor inside brain causes contrast in diffusion images, which depends on the relative orientation of the diffusion gradients and the subject. Because the trace of a tensor is invariant upon rotation, measurement of this trace can reduce the orientation effect. A family of imaging pulse sequences is presented in which the signal intensity is weighted by the trace of the diffusion tensor in a single scan. The methods are demonstrated for chicken gizzard in several orientations with respect to the gradient frame of reference, and for ischemic injury in cat brain after middle cerebral artery occlusion. The sensitivity of the techniques to the presence of background gradients is measured and discussed in detail. As a result, pulse sequences are suggested that provide reliable diffusion constants in both homogeneous and inhomogeneous magnetic fields. The efficiency of the techniques for clinical application is also evaluated.     

Determination of tissue optical properties by steady-state spatial frequency-domain reflectometry

A new non-invasive method to measure the optical properties of biological tissue is described. This method consists of illuminating the investigated sample with light which is spatially periodically modulated in intensity. The spatial modulation of the backscattered light and the diffuse reflectivity of the sample, both detected with an imaging technique, are used to deduce the absorption and reduced scattering coefficient from a table generated by Monte Carlo simulations. This principle has three major advantages: Firstly, it permits the immediate acquisition of the average values of the optical coefficients over a relatively large area (typ. 20 mm in diameter), thus avoiding the perturbations generated by small tissue heterogeneities; It also provides good flexibility for measuring the optical coefficients at various wavelengths and it does not require the use of a detector with a large dynamic range. The method was first validated on phantoms with known optical properties. Finally, we measured the optical properties of human skin at 400 nm, 500 nm, 633 nm and 700 nm in vivo.     

Synthesis,Physicochemical Properties,and Cytotoxicity of a Series of 5′-Ester Prodrugs of 5-Iodo-2′-deoxyuridine

Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU.     

DWI、IVIM参数与脑胶质瘤患儿肿瘤标志物水平相关性

目的 探究扩散加权成像(diffusion weighted imaging, DWI)、体素不相干运动扩散加权成像(diffusion-weighted imaging of voxel incoherent motion, IVIM)参数与脑胶质瘤患儿肿瘤标志物水平相关性及诊断价值。方法 选取于我院进行诊断的疑似脑胶质瘤患儿89例,以病理检查为金标准,最终确诊脑胶质瘤患儿62例为观察组,其余27例为对照组。所有研究对象均进行DWI技术、IVIM技术检查,酶联免疫吸附实验法检测糖链抗原125(carbohydrate antigen 125,CA125)、表皮生长因子(epidermal growth factor, EGF)、癌胚抗原(carcinoembryonic antigen, CEA)水平,对比不同病情患儿表观弥散系数(apparent dispersion coefficient, ADC)、相对脑血容量(relative cerebral blood volume, rCBV)、真实水分子弥散系数(true water molecular dispersion coe...     

A multiple-pathway model for the diffusion of drugs in skin

A mathematical model for the diffusion of drugs in skin is presented.The penetration of the drug by both transcellular and intercellularpathways, as well as its interchange between these pathways,is considered. A pharmacologically motivated asymptotic limitis identified and analysed to obtain, in particular, an analyticalexpression for the flux of drug to the blood at steady state.Relevant model data is discussed, and some numerical resultsare also presented.     

Evidence for a glycerol pathway through aquaporin 1 (CHIP28) channels

Permeabilities to glycerol and small non-electrolytes of three Aquaporin 1 CHIP (AQP1) water channels were measured in AQP1 cRNA-injected Xenopus laevis oocytes and in human AQP1 channels reconstituted in proteoliposomes. By an osmotic swelling assay, significant increases of ethylene glycol, glycerol and 1,3-propanediol apparent permeability coefficients (P_solutes) were found in oocytes expressing human, rat and frog AQP1. p-Chloromercuribenzene sulphonate (PCMBS) and CuSO₄ inhibited, by 95% and 58% respectively, apparent glycerol permeability (P _gly) in oocytes expressing human AQP1. pCMBS inhibition was reversed by -mercaptoethanol and CuSO₄ inhibition was partly reversed by the Cu²⁺-binding peptide Gly-Gly-His. Tritiated glycerol uptakes confirmed the augmented P _gly value of AQP1 cRNA-injected oocytes. In contrast, no increases of urea, meso-erythritol, D- or L-threitol, xylitol and mannitol uptakes were detected. Stopped-flow light scattering experiments performed with human AQP1 proteoliposomes also revealed a much greater increase of P _gly than did those with protein-free liposomes; the initial rate of proteoliposomes also swelling was inhibited by 96.2% with HgCl₂ and by 72.5% with CuSO₄. In AQP1 cRNA-injected oocytes and in proteoliposomes, the value of the glycerol reflection coefficient was 0.74–0.80, indicating that water and glycerol share the same pathway. All these results provide strong evidence that water and certain small solutes permeate the AQP1 channels expressed at the surface of X. laevis oocytes or reconstituted in proteoliposomes. The urea exclusion suggests that the selectivity of the AQP1 channels not only depends on the size of the solutes but probably also on their flexibility and their ability to form H-bonds.     

p-Amino salicylic acid — oxidized cellulose system: a model for long term drug delivery

The immobilization of p-amino salicylic acid (PASA) on periodic oxidized cellulose (O.C) as a biocompatible carrier was investigated. The immobilization of the PASA is based on Schiff's base formation between the amino group of PASA and the aldehyde group of O.C. The in vivo and in vitro release of p-amino salicylic acid was studied. Such a system may be useful for the sustained delivery of the drugs in the body, since O.C. itself is a biosoluble carrier.     

Advection and Diffusion of Substances in Biological Tissues With Complex Vascular Networks

For highly diffusive solutes the kinetics of blood–tissue exchange is only poorly represented by a model consisting of sets of independent parallel capillary–tissue units. We constructed a more realistic multicapillary network model conforming statistically to morphometric data. Flows through the tortuous paths in the network were calculated based on constant resistance per unit length throughout the network and the resulting advective intracapillary velocity field was used as a framework for describing the extravascular diffusion of a substance for which there is no barrier or permeability limitation. Simulated impulse responses from the system, analogous to tracer water outflow dilution curves, showed flow-limited behavior over a range of flows from about 2 to 5 ml min^–1 g^–1, as is observed for water in the heart in vivo. The present model serves as a reference standard against which to evaluate computationally simpler, less physically realistic models. The simulated outflow curves from the network model, like experimental water curves, were matched to outflow curves from the commonly used axially distributed models only by setting the capillary wall permeability–surface area (PS) to a value so artifactually low that it is incompatible with the experimental observations that transport is flow limited. However, simple axially distributed models with appropriately high PSs will fit water outflow dilution curves if axial diffusion coefficients are set at high enough values to account for enhanced dispersion due to the complex geometry of the capillary network. Without incorporating this enhanced dispersion, when applied to experimental curves over a range of flows, the simpler models give a false inference that there is recruitment of capillary surface area with increasing flow. Thus distributed models must account for diffusional as well as permeation processes to provide physiologically appropriate parameter estimates. © 2000 Biomedical Engineering Society. PAC00: 8719-j, 8710+e     

Predicting development of sustained unresponsiveness to milk oral immunotherapy using epitope-specific antibody binding profiles

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