Perfusion and diffusion MRI of glioblastoma progression in a four-year prospective temozolomide clinical trial

RESUME BUT Cette étude a été menée sur le suivi de patients traités pour un glioblastome nouvellement diagnostiqué. Son objectif a été de déterminer l'impact des séquences de perfusion et de diffusion en imagerie par résonance magnétique (IRM). Un intérêt particulier a été porté au potentiel de ces nouvelles techniques d'imagerie dans l'anticipation de la progression de la maladie. En effet, l'intervalle de temps libre de progression est une mesure alternative de pronostic fréquemment utilisée. MATERIEL ET METHODE L'étude a porté sur 41 patients participant à un essai clinique de phase II de traitement par temozolomide. Leur suivi radiologique a comporté un examen IRM dans les 21 à 28 jours après radiochimiothérapie et tous les 2 mois par la suite. L'évaluation des images s'est faite sur la base de l'évaluation de l'effet de masse ainsi que de la mesure de la taille de la lésion sur les images suivantes : T1 avec produit de contraste, T2, diffusion, perfusion. Afin de déterminer la date de progression de la maladie, les critères classiques de variation de taille adjoints aux critères cliniques habituels ont été utilisés. RESULAT 311 examens IRM ont été revus. Au moment de la progression (32 patients), une régression multivariée selon Cox a permis de déterminer deux paramètres de survie : diamètre maximal en T1 (p>0.02) et variation de taille en T2 (p<0.05). L'impact de la perfusion et de la diffusion n'a pas été démontré de manière statistiquement significative. CONCLUSION Les techniques de perfusion et de diffusion ne peuvent pas être utilisées pour anticiper la progression tumorale. Alors que la prise de décision au niveau thérapeutique est critique au moment de la progression de la maladie, l'IRM classique en T1 et en T2 reste la méthode d'imagerie de choix. De manière plus spécifique, une prise de contraste en T1 supérieure à 3 cm dans son plus grand diamètre associée à un hypersignal T2 en augmentation forment un marqueur de mauvais pronostic.

Mucosal healing and deep remission: What does it mean?

The use of specific terms under different meanings and varying definitions has always been a source of confusion in science. When we point our efforts towards an evidence based medicine for inflammatory bowel diseases (IBD) the same is true: Terms such as "mucosal healing" or "deep remission" as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are altered. It appears to be useful to first have a look at the development of terms and their definitions, to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and trials. The purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the terms. It may also lead to a better defined use of those terms for future studies. The terms "mucosal healing" and "deep remission" have been introduced in recent years as new therapeutic targets in the treatment of IBD patients. Several clinical trials, cohort studies or inception cohorts provided data that the long term disease course is better, when mucosal healing is achieved. However, it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical remission. Clinical trials are under way to answer this question. Attention should be paid to clearly address what levels of IBD activity are looked at. In the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists.

Surface characterization techniques for determining the root-mean-square roughness and power spectral densities of optical components

Surface topography and light scattering were measured on 15 samples ranging from those having smooth surfaces to others with ground surfaces. The measurement techniques included an atomic force microscope, mechanical and optical profilers, confocal laser scanning microscope, angle-resolved scattering, and total scattering. The samples included polished and ground fused silica, silicon carbide, sapphire, electroplated gold, and diamond-turned brass. The measurement instruments and techniques had different surface spatial wavelength band limits, so the measured roughnesses were not directly comparable. Two-dimensional power spectral density (PSD) functions were calculated from the digitized measurement data, and we obtained rms roughnesses by integrating areas under the PSD curves between fixed upper and lower band limits. In this way, roughnesses measured with different instruments and techniques could be directly compared. Although smaller differences between measurement techniques remained in the calculated roughnesses, these could be explained mostly by surface topographical features such as isolated particles that affected the instruments in different ways.

Electrical colonic stimulation reduces mean transit time in a porcine model.

Abstract Electrical stimulation is a new way to treat digestive disorders such as constipation. Colonic propulsive activity can be triggered by battery operated devices. This study aimed to demonstrate the effect of direct electrical colonic stimulation on mean transit time in a chronic porcine model. The impact of stimulation and implanted material on the colonic wall was also assessed. Three pairs of electrodes were implanted into the caecal wall of 12 anaesthetized pigs. Reference colonic transit time was determined by radiopaque markers for each pig before implantation. It was repeated 4 weeks after implantation with sham stimulation and 5 weeks after implantation with electrical stimulation. Aboral sequential trains of 1-ms pulse width (10 V; 120 Hz) were applied twice daily for 6 days, using an external battery operated stimulator. For each course of markers, a mean value was computed from transit times obtained from individual pig. Microscopic examination of the caecum was routinely performed after animal sacrifice. A reduction of mean transit time was observed after electrical stimulation (19 +/- 13 h; mean +/- SD) when compared to reference (34 +/- 7 h; P = 0.045) and mean transit time after sham stimulation (36 +/- 9 h; P = 0.035). Histological examination revealed minimal chronic inflammation around the electrodes. Colonic transit time measured in a chronic porcine model is reduced by direct sequential electrical stimulation. Minimal tissue lesion is elicited by stimulation or implanted material. Electrical colonic stimulation could be a promising approach to treat specific disorders of the large bowel.

Bistability driven by Gaussian colored noise: First-passage times

Herein we present a calculation of the mean first-passage time for a bistable one-dimensional system driven by Gaussian colored noise of strength D and correlation time ¿c. We obtain quantitative agreement with experimental analog-computer simulations of this system. We disagree with some of the conclusions reached by previous investigators. In particular, we demonstrate that all available approximations that lead to a state-dependent diffusion coefficient lead to the same result for small D¿c.

Giant acceleration of free diffusion by use of titled periodic potentials

The effective diffusion coefficient for the overdamped Brownian motion in a tilted periodic potential is calculated in closed analytical form. Universality classes and scaling properties for weak thermal noise are identified near the threshold tilt where deterministic running solutions set in. In this regime the diffusion may be greatly enhanced, as compared to free thermal diffusion with, for a realistic experimental setup, an enhancement of up to 14 orders of magnitude.

Exact solution to the mean exit time problem for free inertial processes driven by Gaussian white noise

We obtain the exact analytical expression, up to a quadrature, for the mean exit time, T(x,v), of a free inertial process driven by Gaussian white noise from a region (0,L) in space. We obtain a completely explicit expression for T(x,0) and discuss the dependence of T(x,v) as a function of the size L of the region. We develop a new method that may be used to solve other exit time problems.

First-passage-time noninteger moments for some diffusion and dichotomous processes

We calculate noninteger moments ¿tq¿ of first passage time to trapping, at both ends of an interval (0,L), for some diffusion and dichotomous processes. We find the critical behavior of ¿tq¿, as a function of q, for free processes. We also show that the addition of a potential can destroy criticality.

Scaling and data collapse for the mean exit time of asset prices

We study theoretical and empirical aspects of the mean exit time (MET) of financial time series. The theoretical modeling is done within the framework of continuous time random walk. We empirically verify that the mean exit time follows a quadratic scaling law and it has associated a prefactor which is specific to the analyzed stock. We perform a series of statistical tests to determine which kind of correlation are responsible for this specificity. The main contribution is associated with the autocorrelation property of stock returns. We introduce and solve analytically both two-state and three-state Markov chain models. The analytical results obtained with the two-state Markov chain model allows us to obtain a data collapse of the 20 measured MET profiles in a single master curve.

Free inertial processes driven by Gaussian noise: Probability distributions, anomalous diffusion and fractal behavior

We study the motion of an unbound particle under the influence of a random force modeled as Gaussian colored noise with an arbitrary correlation function. We derive exact equations for the joint and marginal probability density functions and find the associated solutions. We analyze in detail anomalous diffusion behaviors along with the fractal structure of the trajectories of the particle and explore possible connections between dynamical exponents of the variance and the fractal dimension of the trajectories.

Mean first-passage times for systems driven by gamma and McFadden dichotomous noise

We consider mean first-passage times (MFPTs) for systems driven by non-Markov gamma and McFadden dichotomous noises. A simplified derivation is given of the underlying integral equations and the theory for ordinary renewal processes is extended to modified and equilibrium renewal processes. The exact results are compared with the MFPT for Markov dichotomous noise and with the results of Monte Carlo simulations.

Finite-size effects in nonequilibrium correlation functions

We have shown that finite-size effects in the correlation functions away from equilibrium may be introduced through dimensionless numbers: the Nusselt numbers, accounting for both the nature of the boundaries and the size of the system. From an analysis based on fluctuating hydrodynamics, we conclude that the mean-square fluctuations satisfy scaling laws, since they depend only on the dimensionless numbers in addition to reduced variables. We focus on the case of diffusion modes and describe some physical situations in which finite-size effects may be relevant.

Modelling diffusion of innovations in a social network

A simple model of diffusion of innovations in a social network with upgrading costs is introduced. Agents are characterized by a single real variable, their technological level. According to local information, agents decide whether to upgrade their level or not, balancing their possible benefit with the upgrading cost. A critical point where technological avalanches display a power-law behavior is also found. This critical point is characterized by a macroscopic observable that turns out to optimize technological growth in the stationary state. Analytical results supporting our findings are found for the globally coupled case.