bluuebunny/crossref_metadata_2025 huggingface dataset:
A Combination of Selective Light Reflection and Fluorescence Modulation in a Cholesteric Polymer Matrix
Authors: Medvedeva Dasha , Bobrovsky Alexey , Boiko Natalia , Shibaev Valery , Zavarzin Igor , Kalik Marina , Krayushkin Mikhail
Published: January 2005

Summary: The phase behavior and optical properties of a cholesteric ternary copolymer, containing nematogenic phenylbenzoate, cholesteric, and photochromic diarylethene side groups, and its mixture with 2 wt.‐% fluorescent dopant were studied. The investigation of the kinetics of a photochemical opening‐cycle process of the photochromic groups in the cholesteric mixture proved the energy transfer from the fluorescent dopant to the photochromic diarylethene groups. It was shown that the fluorescence intensity of the fluorescent dopant could be controlled by the portion of the “closed” form of the diarylethene groups. During the photocyclization of the photochromic groups a “degeneration” of the selective light reflection of the cholesteric matrix is observed.

Fluorescence‐resonance energy transfer makes possible the process of photosensitization of the back ring‐opening photoreaction of the photochromic diarylethene groups in the cholesteric polymer matrix.

image

Fluorescence‐resonance energy transfer makes possible the process of photosensitization of the back ring‐opening photoreaction of the photochromic diarylethene groups in the cholesteric polymer matrix.
60th Birthday of Prof. Dr. Dr. h.c. Heino Finkelmann
Authors: Mülhaupt Rolf
Published: January 2005

This section contains news of the macromolecular community all over the world. Articles about, for example, people, projects, and market trends are welcome. Suggestions should be sent to the editorial office of the Macromolecular journals, preferably by E‐mail to macromol@wiley‐vch.de. The editorial office decides which articles will be published.
Dynamic decision problem structuring
Authors: Corner James , Buchanan John , Henig Mordecai
Published: January 2005

This paper develops a conceptualization of decision problem structuring which synthesizes a number of models and approaches cited in the decision‐making literature in general and the multi‐criteria literature in particular. The approach advocates a dynamic interaction between criteria and alternatives as a decision‐maker understands his preferences and expands the set of alternatives. This approach endeavours to bridge the gap between prescriptive and descriptive decision problem structuring. It is prescriptive in its orientation, recommending an approach based on earlier prescriptive work. However, the approach is also validated empirically, based on the descriptive decision‐making literature and reported case studies of actual decision‐making. Copyright © 2001 John Wiley & Sons, Ltd.
Relative performance as a strategic commitment mechanism
Authors: Miller Nolan , Pazgal Amit
Published: January 2005

Can managers' personality traits be of use to profit maximizing firm owners? We investigate the case where managers have a variety of attitudes toward relative performance that are indexed by their type. We consider two stage games where profit maximizing owners select managers in the first stage, and these managers, knowing each other's types, compete in a duopoly game in the second stage. The equilibria of various types of competition are derived and comparisons are made to the standard case where managers are profit maximizers. We show that managers' types can be used as a strategic commitment device that can increase firm profits in certain environments. Copyright © 2002 John Wiley & Sons, Ltd.
Strategic behavior in a service industry
Authors: Ilmakunnas Pekka
Published: January 2005

A model of service duopoly is formulated, where the arrival of customers and their service time in the firm are stochastic. The firms first choose the service capacity, and given the capacity they then choose the price in a Bertrand competition. Capacity choices have a negative externality on the competitor, since increased capacity in one firm decreases its expected full price (price plus cost of waiting) and leads to a flow of customers from the other firm. If the firms choose capacities strategically, it is optimal to underinvest compared to the non‐strategic case, but this result may arise in different ways. By underinvesting the firms commit themselves to longer queues (lower quality) to relax price competition. Copyright © 2002 John Wiley & Sons, Ltd.
Lancaster's characteristics approach revisited: product selection using non‐parametric methods
Authors: Fernandez‐Castro Angel S. , Smith Peter C.
Published: January 2005

In consumer theory, the principles of Lancaster's characteristics approach and hedonic pricing appear to offer the most promising insight into choice when qualitative aspects are important. The paper reconciles these principles with the family of non‐parametric frontier estimation methods known as data envelopment analysis. It is shown that, with some straightforward adjustments, DEA is entirely consistent with the characteristics view of consumer choice found in the economics literature. In making Lancaster's ideas operational, the paper also addresses the theoretical concern voiced by Lancaster about combining indivisible products. The principles are illustrated with a case study involving the comparison of diesel cars. The paper concludes that the user will ultimately have to apply some judgement in choosing between competing efficient products. However, the analysis should help to restrict the number of products to be assessed to manageable proportions. Copyright © 2002 John Wiley & Sons, Ltd.
Homogenization of the linearized system of elasticity in anisotropic heterogeneous thin cylinders
Authors: Sili Ali
Published: January 2005

This paper is the second of the two announced in our Note (Sili A, [16]). It generalizes to the linearized system of elasticity the results of our previous work (Sili, 2000 [15]) on the heat equation. We study the asymptotic analysis, as ϵ tends to zero, of the solution uϵ of the linearized system of elasticity posed on a composite elastic cylindrical domain Ωϵ with radius ϵ and height L. The heterogeneities of the material are assumed to be periodic with a period ϵ along the cylinder axis and with a period ϵ2 along the sections of the cylinder. It is shown that the limit problem is a system in which appear two entities: the first one (u, v, w) corresponds to the reduction of dimension 3d–1d while the second one (û, v̂, ŵ) takes into account the homogenization process. Moreover, a corrector result is given. Copyright © 2002 John Wiley & Sons, Ltd.
On a boundary variational inequality of the second kind modelling a friction problem
Authors: Guediri Hocine
Published: January 2005

A scalar contact problem with friction governed by the Yukawa equation is reduced to a boundary variational inequality. The presence of the non‐differentiable friction functional causes some difficulties when approximated. We present two methods to overcome this difficulty. The first one is a regularization leading to a non‐linear boundary variational equation, for which we propose an iterative procedure, whereas the second method is based on the boundary mixed variational formulation involving Lagrange multipliers. We propose Uzawa's algorithm to compute the saddle point of the corresponding boundary Lagrangian and investigate the discretization of various formulations by the boundary element Galerkin method. Convergence of the boundary element solution is proved and a convergence order is obtained. Copyright © 2002 John Wiley & Sons, Ltd.
Non‐linear initial boundary value problemsof hyperbolic–parabolic type. A general investigationof admissible couplings between systems of higher order. Part 1: linear theory
Authors: Ebenfeld Stefan
Published: January 2005

In this article (which is divided in three parts) we investigate the non‐linear initial boundary value problems (1.2) and (1.3). In both cases we consider coupled systems where each system is of higher order and of hyperbolic or parabolic type.

Our goal is to characterize systematically all admissible couplings between systems of higher order and different type.

By an admissible coupling we mean a condition that guarantees the existence, uniqueness and regularity of solutions to the respective initial boundary value problem.

In part 1 at hand, we develop the underlying theory of linear hyperbolic and parabolic initial boundary value problems. Testing the PDEs with suitable functions we obtain a priori estimates for the respective solutions. In particular, we make use of the regularity theory for linear elliptic boundary value problems that was previously developed by the author. In part 2, we prove the local in time existence, uniqueness and regularity of solutions to the quasilinear initial boundary value problem (1.2) using the so‐called energy method. In the above sense, the regularity assumptions about the coefficients and right‐hand sides define the admissible couplings. In part 3, we extend the results of part 2 to the non‐linear initial boundary value problem (1.3). In particular, the assumptions about the respective parameters correspond to the previous regularity assumptions and hence define the admissible couplings now. Moreover, we exploit the assumptions about the respective parameters for the case of two coupled systems. Copyright © 2002 John Wiley & Sons, Ltd.
Phase‐field systems for multi‐dimensional Prandtl–Ishlinskii operators with non‐polyhedral characteristics
Authors: Sprekels Jürgen , Krejčí Pavel
Published: January 2005

Hysteresis operators have recently proved to be a powerful tool in modelling phase transition phenomena which are accompanied by the occurrence of hysteresis effects. In a series of papers, the present authors have proposed phase‐field models in which hysteresis non‐linearities occur at several places. A very important class of hysteresis operators studied in this connection is formed by the so‐called Prandtl–Ishlinskii operators. For these operators, the corresponding phase‐field systems are in the multi‐dimensional case only known to admit unique solutions if the characteristic convex sets defining the operators are polyhedrons. In this paper, we use approximation techniques to extend the known results to multi‐dimensional Prandtl–Ishlinskii operators having non‐polyhedral convex characteristicsets. Copyright © 2002 John Wiley & Sons, Ltd.
On the Stokes system and on the biharmonic equation in the half‐space: an approach via weighted Sobolev spaces
Authors: Boulmezaoud Tahar Z.
Published: January 2005

In this paper, we investigate the Stokes system and the biharmonic equation in a half‐space of ℝn. Our approach rests on the use of a family of weighted Sobolev spaces as a framework for describing the behaviour at infinity. A complete class of existence, uniqueness and regularity results for both the problems is proved. The proofs are mainly based on the principle of reflection. Copyright © 2002 John Wiley & Sons, Ltd.
Optimal control of singular systems via piecewise linear polynomial functions
Authors: Razzaghi Mohsen , Marzban Hamid‐Reza
Published: January 2005

A method for finding the optimal control of linear singular systems with a quadratic cost functional using piecewise linear polynomial functions is discussed. The state variable, state rate, and the control vector are expanded in piecewise linear polynomial functions with unknown coefficients. The relation between the coefficients of the state rate with state variable is provided and the necessary condition of optimality is derived as a linear system of algebraic equations in terms of the unknown coefficients of the state and control vectors. A numerical example is included to demonstrate the validity and the applicability of the technique. Copyright © 2002 John Wiley & Sons, Ltd.
Legendre wavelets method for constrained optimal control problems
Authors: Razzaghi Mohsen , Yousefi Sohrabali
Published: January 2005

A numerical method for solving non‐linear optimal control problems with inequality constraints is presented in this paper. The method is based upon Legendre wavelet approximations. The properties of Legendre wavelets are first presented. The operational matrix of integration and the Gauss method are then utilized to reduce the optimal control problem to the solution of algebraic equations. The inequality constraints are converted to a system of algebraic equalities; these equalities are then collocated at the Gauss nodes. Illustrative examples are included to demonstrate the validity and applicability of the technique. Copyright © 2002 John Wiley & Sons, Ltd.
An upper and lower solution approach for singular boundary value problems with sign changing non‐linearities
Authors: Agarwal Ravi P. , O'Regan Donal
Published: January 2005

We obtain via Schauder's fixed point theorem new results for singular second‐order boundary value problems where our non‐linear term f(t,y,z) is allowed to change sign. In particular, our problem may be singular at y=0, t=0 and/or t=1. Copyright © 2002 John Wiley & Sons, Ltd.
On a non‐uniqueness in fragmentation models
Authors: Banasiak J.
Published: January 2005

Equations of fragmentation describing e.g. the polymer degradation, despite their apparent simplicity, have numerous non‐typical features. One of them is the existence of multiple solutions. In this paper, applying classical results of Hille and Phillips, we explain their occurrence and prove that nevertheless the uniqueness holds for a large class of physically reasonable solutions. Copyright © 2002 John Wiley & Sons, Ltd.
Modern proton‐detected 1D 1H–15N NMR experiments. Application to the measurement of 1H,15N coupling constants at natural abundance
Authors: Parella Teodor , Belloc Jordi
Published: January 2005

Non‐selective and selective versions of several proton‐detected 1D NMR experiments to be applied to 15N are proposed. Clean, artifact‐free 1D spectra are easily obtained by the effective coherence selection by pulsed‐field gradients and the attainable sensitivity is maximized using modern pulse schemes. Despite the low sensitivity inherent to 15N NMR spectroscopy, the successful application of these experiments is demonstrated for resonance assignments and accurate measurement of both one‐bond and long‐range proton–nitrogen coupling constants on a model tripeptide at natural abundance. Copyright © 2001 John Wiley & Sons, Ltd.
A rare occurrence of a β‐turn in an amyloid βA4 peptide
Authors: Tauro Savita , Coutinho Evans , Srivastava Sudha
Published: January 2005

The fragment β(25–35) of the amyloid β‐peptide, like its parent βA4, has shown neurotrophic and late neurotoxic activities in cultured cells. The 3D structure of this important peptide was examined by 1H and 13C 2D‐NMR and MD simulations in DMSO‐d6 and water. The NMR parameters of chemical shift, 3J(N,Hα) coupling constants, temperature coefficients of NH chemical shifts and the pattern of intra and inter‐residue NOEs were used to deduce the structures. In DMSO‐d6, the peptide was found to take up a type I β‐turn around the C‐terminal residues Ile8–Gly9–Leu10–Met11, whereas in water at pH 5.5, it adopts a random coil conformation. This is only the second report of a β‐turn in the β‐amyloid class of peptides. The solution structures generated using restrained molecular dynamics were refined by MARDIGRAS to an R factor of 0.33 in the case of DMSO‐d6 and to 0.56 for water. Copyright © 2002 John Wiley & Sons, Ltd.
Computational mechanics of the steel–concrete interface
Authors: Ben Romdhane M. R. , Ulm F.‐J.
Published: January 2005

Concrete cracking in reinforced concrete structures is governed by two mechanisms: the activation of bond forces at the steel–concrete interface and the bridge effects of the reinforcement crossing a macro‐crack. The computational modelling of these two mechanisms, acting at different scales, is the main objective of this paper. The starting point is the analysis of the micro‐mechanisms, leading to an appropriate choice of (measurable) state variables describing the energy state in the surface systems: on the one side the relative displacement between the steel and the concrete, modelling the bond activation; on the other hand, the crack opening governing the bridge effects. These displacement jumps are implemented in the constitutive model using thermodynamics of surfaces of discontinuity.

On the computational side, the constitutive model is implemented in a discrete crack approach. A truss element with slip degrees of freedom is developed. This degree of freedom represents the relative displacement due to bond activation. In turn, the bridge effect is numerically taken into account by modifying the post‐cracking behaviour of the contact elements representing discrete concrete cracks crossed by a rebar. First simulation results obtained with this model show a good agreement in crack pattern and steel stress distribution with micro‐mechanical results and experimental results. Copyright © 2001 John Wiley & Sons, Ltd.
A visco‐plastic constitutive model for granular soils modified according to non‐local and gradient approaches
Authors: di Prisco C. , Imposimato S. , Aifantis E. C.
Published: January 2005

An already available non‐associated elastic–viscoplastic constitutive model with anisotropic strain hardening is modified in order to describe both the constitutive parameter dependency on relative density and the spatio‐temporal evolution of strain localization. To achieve this latter goal, two distinct but similar approaches are introduced: one inspired by the gradient theory and one by the non‐local theory. A one‐dimensional case concerning a simple shear test for a non‐homogeneous infinitely long dense sand specimen is numerically discussed and a finite difference scheme is employed for this purpose. The results obtained by following the two different approaches are critically analysed and compared. Copyright © 2001 John Wiley & Sons, Ltd.
Explicit solutions for the instantaneous undrained contraction of hollow cylinders and spheres in porous elastoplastic medium
Authors: Giraud A. , Homand F. , Labiouse V.
Published: January 2005

In this article we present closed‐form solutions for the undrained variations in stress, pore pressure, deformation and displacement inside hollow cylinders and hollow spheres subjected to uniform mechanical pressure instantaneously applied to their external and internal boundary surfaces. The material is assumed to be a saturated porous medium obeying a Mohr–Coulomb model failure criterion, exhibiting dilatant plastic deformation according to a non‐associated flow rule which accounts for isotropically strain hardening or softening. The instantaneous response of a porous medium submitted to an instantaneous loading is undrained, i.e. without any fluid mass exchange. The short‐term equilibrium problem to be solved is now formally identical to a problem of elastoplasticity where the constitutive equations involve the undrained elastic moduli and particular equivalent plastic parameters. The response of the model is presented (i) for extension and compression undrained triaxial tests, and (ii) for unloading problems of hollow cylinders and spheres through the use of appropriately developed closed‐form solutions. Numerical results are presented for a plastic clay stone with strain hardening and an argilite with strain softening. The effects of plastic dilation, of the strain softening law and also of geometry of the cavity on the behaviour of the porous medium have been underlined. Analytical solutions provide valuable benchmarks enabling various numerical methods in undrained conditions with a finite boundary to be verified. Copyright © 2002 John Wiley & Sons, Ltd.
Integration and calibration of a plasticity model for granular materials
Authors: Jacobsson L. , Runesson K.
Published: January 2005

A new macroscopic constitutive model for non‐cohesive granular materials, with the focus on coarse‐sized materials (railway ballast), is presented. The model is based on the concepts of rate‐independent isotropic plasticity. The Backward Euler rule is used for integrating the pertinent evolution equations. The resulting incremental relations are solved in the strain space that is extended with the internal (hardening) variables. The model is calibrated using data from Conventional Triaxial Compression (CTC) tests, carried out at the University of Colorado at Boulder. A function evaluation method is used for the optimization, whereby a ‘multi‐vector’ strategy for choosing the appropriate start vector is proposed. Copyright © 2002 John Wiley & Sons, Ltd.
Image‐based modelling and analysis of microstructures for two‐scale problems in geomechanics
Authors: Terada Kenjiro , Kyoya Takashi , Kazama Motoki , Lee Kiho , Oyang Lizhu
Published: January 2005

This paper focuses on the geometry modelling and numerical analysis of microstructures of geomaterials employing the concept of image‐based engineering. The novel modelling and analysis techniques with digital images are incorporated with the mathematical homogenization method to study the interaction between individual phases, each of whose shape and spatial distribution are irregular. Owing to the distinctive features of these computational techniques, the evaluation of homogenized properties for geomaterials provides the reliable information about the micro‐ or macroscopic mechanical behaviours for engineering practice. It is, naturally, inevitable that engineers' demands on safety and efficient design place emphasis on quantitative estimates for these values. Thus, calibration accompanied with actual measurements comes within the scope of this study so that these properties would be realistic and practical from the engineering viewpoints. Copyright © 2002 John Wiley & Sons, Ltd.
Fundamental solutions for a fluid‐saturated, transversely isotropic, poroelastic solid
Authors: Taguchi I. , Kurashige M.
Published: January 2005

The fundamental solutions were obtained for step‐like point forces acting in three orthogonal directions and an instantaneous fluid point source in a fluid‐saturated, porous, infinite solid of transversely isotropic elasticity and permeability. After expressing the governing equations in the form of matrix in the Laplace space, we employed Kupradze's method together with the triple Fourier transforms. This method reduces the simultaneous partial differential equations with respect to three displacement components and a pore fluid pressure to a differential equation in terms of only one potential scalar function, which can be operationally solved in the transformed space. After the Laplace inversion of the potential, the residue theorem was applied to its Fourier inverse transform with respect to one of the transformation variables. The Fourier transforms with respect to two other variables were rewritten into the Hankel transforms. Copyright © 2002 John Wiley & Sons, Ltd.
Source signature and elastic waves in a half‐space under a sustainable line‐concentrated impulsive normal force
Authors: Ziv Moche
Published: January 2005

First, the response of an ideal elastic half‐space to a line‐concentrated impulsive normal load applied to its surface is obtained by a computational method based on the theory of characteristics in conjunction with kinematical relations derived across surfaces of strong discontinuities. Then, the geometry is determined of the obtained waves and the source signature—the latter is the imprint of the spatiotemporal configuration of the excitation source in the resultant response. Behind the dilatational precursor wave, there exists a pencil of three plane waves extending from the vertex at the impingement point of the precursor wave on the stress‐free surface of the half‐space to three points located on the other two boundaries of the solution domain. These four wave‐arresting points (end points) of the three plane waves constitute the source signature. One wave is an inhibitor front in the behaviour of the normal stress components and the particle velocity, while in the behaviour of the shear stress component, it is a surface‐axis wave. The second is a surface wave in the behaviour of the horizontal components of the dependent variables, while the third is an inhibitor wave in the behaviour of the shear stress component. An inhibitor wave is so named, since beyond it, the material motion is dying or becomes uniform. A surface‐axis wave is so named, since upon its arrival, like a surface wave, the dependent variable in question features an extreme value, but unlike a surface wave, it exists in the entire depth of the solution domain. It is evident from this work that Saint‐Venant's principle for wave propagation problems cannot be formulated; therefore, the above results are a consequence of the particular model proposed here for the line‐concentrated normal load. Copyright © 2002 John Wiley & Sons, Ltd.
Failure criteria of anisotropically damaged materials based on the critical plane concept
Authors: Mróz Zenon , Maciejewski Jan
Published: January 2005

The damage state of a cracked material is assumed to be specified by crack density distribution on physical planes. The critical plane approach is used with account for damaged and intact area fractions on the plane. The maximum of failure function is specified for all potential failure planes and the critical plane orientation is determined. The resulting failure condition is applied to study strength evolution for triaxially compressed specimens with varying orientation of principal stress and damage tensor axes. Both Coulomb and non‐linear failure conditions of Mohr type are applied to specify the representative critical plane. A general stress state is considered and the failure condition is specified for different relative orientations of orthotropy and principal stress axes. Copyright © 2002 John Wiley & Sons, Ltd.
Modelling of hygro‐thermal behaviour and damage of concrete at temperature above the critical point of water
Authors: Gawin D. , Pesavento F. , Schrefler B. A.
Published: January 2005

In this paper, a model for the analysis of the behaviour of concrete at temperature largely exceeding critical point of water, is presented. In this temperature range liquid phase, i.e. capillary phase, and gas phase cannot be distinguished and only the latter exists. Consequently, capillary pressure has no more physical meaning above this point and liquid water is present only as physically adsorbed water. In this work, we give a different physical interpretation to the capillary pressure and use it still for the description of the hygrometric state of concrete in the zone, where temperature exceeds the critical point of water. Considerable thermal dilatation of the liquid water and the real behaviour of water vapour close to critical temperature are taken into account. Moreover, a special switching procedure in order to avoid the Stefan‐like problem, which subsequently arises, is described and employed in the calculations. Finally, several numerical examples demonstrating the robustness of the adopted solution have been shown. Copyright © 2002 John Wiley & Sons, Ltd.
In vivo and in vitro NMR spectroscopy reveal a putative novel inborn error involving polyol metabolism
Authors: Moolenaar Sytske H. , Knaap Marjo S. van der , Engelke Udo F. H. , Pouwels Petra J. W. , Janssen‐Zijlstra Fokje S. M. , Verhoeven Nanda M. , Jakobs Cornelis , Wevers Ron A.
Published: January 2005

In vivo NMR spectroscopy was performed on the brain of a patient with a leukoencephalopathy, revealing unknown resonances between 3.5 and 4.0 ppm. In addition, urine and CSF of the patient were measured using high‐resolution NMR spectroscopy. Also in these in vitro spectra, unknown resonances were observed in the 3.5–4.0 ppm region. Homonuclear 1H two‐dimensional J‐resolved spectroscopy (JRES) and 1H–1H correlation spectroscopy (COSY) were performed on the patient's urine for more accurate assignment of resonances. The NMR spectroscopic studies showed that the unknown resonances could be assigned to arabinitol and ribitol. This was confirmed using gas chromatography. The arabinitol was identified as D‐arabinitol. The patient is likely to suffer from an as yet unknown inborn error of metabolism affecting D‐arabinitol and ribitol metabolism. The primary molecular defect has not been found yet. Urine spectra of patients suffering from diabetes mellitus or galactosemia were recorded for comparison. Resonances outside the 3.2–4.0 ppm region, which are the most easy to recognize in body fluid spectra, allow easy recognition of various sugars and polyols. The paper shows that NMR spectroscopy in body fluids may help identifying unknown resonances observed in in vivo NMR spectra. Copyright © 2001 John Wiley & Sons, Ltd.

Abbreviations used:

Cho

choline‐containing compounds

COSY

1H–1H correlation spectroscopy

Cr

creatine

CSF

cerebrospinal fluid

GC

gas chromatography

Glx

glutamine and glutamate

JRES

homonuclear 1H two‐dimensional J‐resolved spectroscopy

Myo‐Ins

myo‐inositol

NAA

N‐acetylaspartate

Scyllo‐Ins

scyllo‐inositol

STEAM

stimulated echo acquisition mode

PRESS

point resolved spectroscopy.
In vivo single‐voxel proton MR spectroscopy in brain lesions with ring‐like enhancement
Authors: Kimura Teruo , Sako Kazuhiro , Gotoh Takumi , Tanaka Kunio , Tanaka Tatsuya
Published: January 2005

It is often difficult to make a correct diagnosis of ring‐like enhanced lesions on Gd‐enhanced MR brain images. To differentiate these lesions using proton MR spectroscopy (1H‐MRS), we retrospectively evaluated the correlation between the 1H‐MR spectra and histopathological findings. We evaluated proton MR spectra obtained from the lesions in 45 patients, including metastasis (n = 19), glioblastoma (n = 10), radiation necrosis (n = 7), brain abscess (n = 5), and cerebral infarction (n = 4). The rate of misdiagnosis was found to be lowest at the threshold level of 2.48 for the (choline containing compounds)/(creatine and phosphocreatine) ratio (Cho/Cr) obtained from the whole lesions, which include the enhanced rim and the non‐enhanced inner region. That is, the positively predictive values of a Cho/Cr greater than 2.48 for diagnosing metastasis or glioblastoma was 88.9 and 60.0%, respectively, and the positively predictive value of a Cho/Cr less than 2.48 for diagnosing radiation necrosis or cerebral infarction was 71.4 and 100%, respectively. For further differentiating between metastasis and glioblastoma, information about the presence and absence of an N‐acetyl‐aspartate (NAA) peak and lipid‐ or lactate‐dominant peak was found to be useful. In 73.7% of metastasis cases a lipid‐dominant peak was observed in the whole lesion without an NAA peak in the inner region, whereas the same pattern was observed in only 10% of the glioblastoma cases.
 Correlation with the histopathological findings showed that a high Cho signal is suggestive of neoplasm. Lipid signal in the non‐enhanced central region was correlated to necrosis. Lactate signals were often observed in glioblastoma, abscess and sometimes metastasis, presumably reflecting the anaerobic glycolysis by the living cells in the ring‐like enhanced rim. Single‐voxel proton MR spectroscopy may serve as a potential tool to provide useful information of differentiation of ring‐like enhanced lesions that cannot be diagnosed correctly using enhanced MR images alone. Copyright © 2001 John Wiley & Sons, Ltd.
Therapeutic efficacy of 5‐fluorouracil‐loaded microspheres on rat glioma: a magnetic resonance imaging study
Authors: Lemaire L. , Roullin V.‐G. , Franconi F. , Venier‐Julienne M.‐C. , Menei P. , Jallet P. , Le Jeune J.‐J. , Benoit J.‐P.
Published: January 2005

The aim of this work was to assess the therapeutic efficacy of an intratumoral bolus injection of 5‐fluorouracil (FU) compared to that of drug loaded in biodegradable microspheres, for the treatment of brain tumour. Experiments were carried out using a fast‐growing C6‐glioma rat model. The therapeutic protocols were performed 12 days after the injection of glioma cells. At this stage, the tumours were installed and the mean volume was 13 ± 2 µl as measured by proton magnetic resonance (MR) imaging. This technique was used for the follow‐up of the tumour volume with respect to time and therapy. In terms of rat survival, both therapies induced a significant 50% increase in animal life span (p < 0.05) compared to animals receiving no drug or unloaded microspheres. Whilst no cure was observed, analysis of the MR images showed that the local and sustained delivery of FU slowed the tumour development in the vicinity of the microspheres by a factor of 3, compared with the bolus intratumoral injection. Copyright © 2001 John Wiley & Sons, Ltd.
Differential sensitivity of two adenocarcinoma xenografts to the anti‐vascular drugs combretastatin A4 phosphate and 5,6‐dimethylxanthenone‐4‐acetic acid, assessed using MRI and MRS
Authors: Beauregard Daniel A. , Pedley R. Barbara , Hill Sally A. , Brindle Kevin M.
Published: January 2005

The effects of two anti‐vascular agents, combretastatin A4 phosphate (CA4P), and 5,6‐dimethylxanthenone‐4‐acetic acid (DMXAA), on the perfusion of two human colon adenocarcinomas implanted in SCID mice, were assessed for up to 3 h using non‐invasive magnetic resonance imaging (MRI) and spectroscopy techniques (MRS). MRI measurements of GdDTPA inflow showed that treatment with CA4P had little effect on the perfusion of HT29 tumours. Localized 31P MRS measurements also showed that the drug had no significant effect on tumour cell energy status, as assessed from the ratio of the integrals of the signals from inorganic phosphate (Pi) and nucleoside triphosphates. However, after treatment with DMXAA, perfusion was reduced and the Pi/NTP ratio increased, indicating that the HT29 tumour is susceptible to the action of this drug. The LS174T tumour model was susceptible to both CA4P and DMXAA, using the criteria of changes in GdDTPA inflow and Pi/NTP ratio. Copyright © 2002 John Wiley & Sons, Ltd.
MRI and fluorescence microscopy of the acute vascular response to VEGF165: vasodilation, hyper‐permeability and lymphatic uptake, followed by rapid inactivation of the growth factor
Authors: Dafni Hagit , Landsman Limor , Schechter Bilha , Kohen Fortune , Neeman Michal
Published: January 2005

Vascular endothelial growth factor (VEGF) is one of the key growth factors regulating tumor angiogenesis and thus it is one of the primary targets for antiangiogenic therapy. The long‐term effects of VEGF include induction of proliferation and migration of endothelial cells, tube formation and maintenance of the immature capillaries. The early effects of VEGF include vasodilation and increased permeability. We hypothesize that the early responses to VEGF can serve to develop a quantitative measure of the activity of VEGF, and therefore may be applicable for monitoring the efficacy of systemic suppression of VEGF signaling during antiangiogenic therapy. For that end we tested the ability of MRI and fluorescence microscopy to detect the early response to intradermal VEGF165 in nude mice. VEGF‐induced local vasodilation and increased permeability was detected by intravenous administration of macromolecular biotin‐BSA‐GdDTPA23 30 min after intradermal administration of VEGF. Contrast leak showed saturation kinetics. Delayed contrast administration (90 min after intradermal administration of VEGF) resulted in low contrast leak and demonstrated that the saturation kinetics is not due to contrast equilibration between plasma and the interstitial space, but rather is due to suppression of vascular permeability. Permeability was restored by a second bolus of VEGF, showing that the saturation kinetics is primarily due to inactivation of the growth factor. Confocal microscopy of fluorescent BSA‐FITC confirmed the permeability changes monitored by MRI. Moreover, confocal microscopy showed efficient lymphatic uptake of the extravasated contrast material specifically in regions of VEGF induced hyper‐permeability. Copyright © 2002 John Wiley & Sons, Ltd.
Breath‐hold perfusion and permeability mapping of hepatic malignancies using magnetic resonance imaging and a first‐pass leakage profile model
Authors: Jackson A. , Haroon H. , Zhu X. P. , Li K. L. , Thacker N. A. , Jayson G.
Published: January 2005

We have applied a novel pharmacokinetic model of the distribution of contrast media to dynamic contrast‐enhanced MRI data from patients with hepatic neoplasms. The model uses data collected during the passage of a bolus of contrast medium and allows breath‐hold image acquisition. The aims of the study were to investigate the feasibility of permeability mapping using the first pass technique and breath‐hold acquisitions, and to examine the reproducibility of the technique and the effect of the liver's dual vascular supply on the assumptions of the model. Imaging was performed in 14 patients with hepatic neoplasms. Dynamic data clearly demonstrated differences in the timing and shape of the contrast medium concentration–time course curve in the systemic arterial and portal venous systems. Mapping of the arrival time (T0) of contrast medium allowed identification of tissue supplied by the hepatic arteries and portal vein. Hepatic tumours all showed typical hepatic arterial enhancement. Repeated measurements of endothelial permeability surface area product (kfp) and relative blood volume (rBV), performed in five patients, showed excellent reproducibility with variance ratios (Vr) of 0.134 and 0.113, respectively. Measurement of enhancing tumour volume was also highly reproducible (Vr = 0.096) and this was further improved by the use ofT0maps to identify pixels supplied by the hepatic artery (Vr = 0.026). Estimates ofkfpand rBV in normal hepatic tissue supplied by the portal vein were highly inaccurate and these pixels were identified by use of theT0parameter and excluded from the analysis. In conclusion, dynamic MRI contrast enhancement combined with a pharmacokinetic model of the distribution of contrast media in the first pass allows us to produce highly reproducible parametric maps ofkfpand rBV from hepatic tumours that are supplied by the hepatic arterial system using breath‐hold acquisitions. Copyright © 2002 John Wiley & Sons, Ltd.
Assessment of protamine‐induced thrombosis of tumor vessels for cancer therapy using dynamic contrast‐enhanced MRI
Authors: Su Min‐Ying , Samoszuk Michael K. , Wang Jun , Nalcioglu Orhan
Published: January 2005

Since the role of angiogenesis in cancer development has been recognized, the study of anti‐angiogenic or anti‐vascular therapeutic agents has become increasingly important for cancer treatment. Selective thrombosis is one approach towards this goal. Since many types of carcinoma accumulate large numbers of degranulating mast cells which will release heparin, intravenously injected protamine may bind to heparin, neutralize its anti‐coagulant effect and induce thrombosis. In this work we studied the formation of thrombosis by using dynamic contrast enhanced MRI. The enhancement kinetics of the contrast medium measured before and after protamine treatment were compared to assess the thrombotic effect. The underlying concept was that if the vessels became clotted, the subsequently injected contrast medium could not be delivered into the tissue to cause enhancement. In addition to the tissue‐specific changes, protamine may also induce systemic effect in the host. The therapy‐induced changes measured in tumors were compared to changes in normal tissues: liver, kidney, and especially the muscle adjacent to tumor. The results showed that protamine induced pronounced changes in the tumor. However, the degree of change measured by MRI was not associated with the results of semiquantitative assessment of thrombosis assessed by histology, perhaps due to the heterogeneous nature of the tumor and the difficulty in sampling sufficient regions histologically. The protamine‐induced temporal effects were also studied. We demonstrated that protamine could induce selective thrombosis in tumors, and that the effect could last for several hours. Dynamic contrast‐enhanced MRI can serve as a suitable means to investigate the mechanism of this novel approach to induce selective thrombosis for anti‐vascular cancer therapy. Copyright © 2002 John Wiley & Sons, Ltd.
Reproducibility of dynamic contrast‐enhanced MRI in human muscle and tumours: comparison of quantitative and semi‐quantitative analysis
Authors: Galbraith Susan M. , Lodge Martin A. , Taylor N. Jane , Rustin Gordon J. S. , Bentzen Søren , Stirling J. James , Padhani Anwar R.
Published: January 2005

The purpose of this study was to determine the reproducibility of dynamic contrast‐enhanced (DCE)‐MRI and compare quantitative kinetic parameters with semi‐quantitative methods, and whole region‐of‐interest (ROI) with pixel analysis. Twenty‐one patients with a range of tumour types underwent paired MRI examinations within a week, of which 16 pairs were evaluable. A proton density‐weighted image was obtained prior to a dynamic series of 30 T1‐weighted spoiled gradient echo images every 11.9 s with an intravenous bolus of gadopentetate dimeglumine given after the third baseline data point. Identical ROIs around the whole tumour and in skeletal muscle were drawn by the same observer on each pair of examinations and used for the reproducibility analysis. Semi‐quantitative parameters, gradient, enhancement and AUC (area under the curve) were derived from tissue enhancement curves. Quantitative parameters (Ktrans, kep, ve) were obtained by the application of the Tofts' model. Analysis was performed on data averaged across the whole ROI and on the median value from individual pixels within the ROI. No parameter showed a significant change between examinations. For all parameters except Ktrans, the variability was not dependent on the parameter value, so the absolute values for the size of changes needed for significance should be used for future reference rather than percentages. The size of change needed for significance in a group of 16 in tumours for Ktrans, kep and ve was −14 to +16%, ±0.20 ml/ml/min (15%) and ±1.9 ml/ml (6%), respectively (pixel analysis), and −16 to +19%, ±0.23 ml/ml/min (16%) and ±1.9 ml/ml (6%) (whole ROI analysis). For a single tumour, changes greater than −45 to +83%, ± 0.78 ml/ml/min (60%) and ± 7.6 ml/ml (24%), respectively, would be significant (pixel analysis). For gradient, enhancement and AUC the size of change needed for significance in tumours was ±0.24 (17%), ±0.05 (6%) and ±0.06 (8%), respectively for a group of 16 (pixel analysis), and ±0.96 (68%), ±0.20 (25%) and ±0.22 (32%) for individuals. In muscle, the size of change needed for significance in a group of 16 for Ktrans, kep and ve was −30 to +44%, ±0.81 ml/ml/min (61%) and ±1.7 ml/ml (13%). For gradient, enhancement and AUC it was ±0.09 (20%), ±0.02 (8%) and ±0.03 (12%). ve, enhancement and AUC are highly reproducible DCE‐MRI parameters. Ktrans, kep and gradient have greater variability, with larger changes in individuals required to be statistically significant, but are nevertheless sufficiently reproducible to detect changes greater than 14–17% in a cohort of 16 patients. Pixel analyses slightly improve reproducibility estimates and retain information about spatial heterogeneity. Reproducibility studies are recommended when treatment effects are being monitored. Copyright © 2002 John Wiley & Sons, Ltd.
Reproducibility of quantitative dynamic MRI of normal human tissues
Authors: Padhani Anwar R. , Hayes Carmel , Landau Sabine , Leach Martin O.
Published: January 2005

The aim of the study was to establish the normal range and to evaluate the reproducibility of dynamic contrast enhanced MRI (DCE‐MRI) parameter estimates in normal human pelvic tissues. Nineteen patients with prostate cancer, undergoing androgen deprivation treatment, had paired DCE‐MRI examinations of the pelvis using spoiled gradient‐echo sequences. Quantitative enhancement parameters were calculated for each examination: transfer constant (Ktrans), leakage space (ve) and maximum contrast medium accumulation (MCMA) of pelvic muscles, bone marrow and fat. Descriptive and reproducibility statistics were calculated: within‐patient standard deviation (wSD), repeatability and within‐patient coefficient of variation (wCV). The femoral head and ischiorectal fat showed large numbers of non‐enhancing pixels (81 and 88%, respectively). The ischial bone marrow had the highest values of kinetic parameter estimates (Ktrans 0.554 min−1, ve 18.5% and MCMA 0.164 mmol/kg). Muscle parameters values were lower (Ktrans 0.126–0.137 min−1, ve 10.6–11.5% and MCMA 0.077–0.086 mmol/kg). The mean difference between paired examinations was not significantly different from zero for any parameter. ve and MCMA had the lowest wCV (between 19 and 29%). For individuals, a log10 Ktrans change of approximately 0.90 in muscles and 0.52 in the ischium would be statistically significant. The corresponding absolute changes for ve are 6.7% in muscle and 13.6% in the ischium. For a group of 19 patients, small changes are statistically significant (muscle log10 Ktrans 0.208 and ve 1.5% and ischium log10 Ktrans 0.123 and ve 3.1%). Fat and the femoral head are unreliable tissues from which to obtain kinetic parameter estimates due to poor enhancement. ve and MCMA have smaller coefficient of variation than Ktrans in muscles and ischium. Reproducibility studies of normal and pathological tissues should be incorporated into clinical research protocols that measure treatment effects by DCE‐MRI techniques. Copyright © 2002 John Wiley & Sons, Ltd.
Combined vascular and extracellular pH imaging of solid tumors
Authors: Bhujwalla Z. M. , Artemov D. , Ballesteros P. , Cerdan S. , Gillies R. J. , Solaiyappan M.
Published: January 2005

The unique physiological environment of solid tumors, frequently characterized by areas of poor flow, hypoxia, high lactate and low extracellular pH (pHe), influences vascularization, invasion and metastasis. Thus, vascularization and the physiological and metabolic environment play permissive (and conversely preventive) roles in invasion and metastasis. By using a multi‐parametric approach of combined vascular and spectroscopic imaging, we can begin to evaluate which combinations of vascular, metabolic and physiological regions in a solid tumor represent the highest ‘metastatic threat’. Here, we present measurements of pHe, vascular volume and permeability from co‐localized regions within a solid tumor. These studies were performed for a group of metastatic (MDA‐MB‐231) and non‐metastatic (MCF‐7) human breast cancer xenografts. In this study, we have demonstrated the feasibility of such an approach, and presented methods of analyses to detect differences in patterns of combined parameters obtained from spatially co‐registered regions in a solid tumor. Copyright © 2002 John Wiley & Sons, Ltd.