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

PURPOSE: This study was performed to determine the impact of perfusion and diffusion magnetic resonance imaging (MRI) sequences on patients during treatment of newly diagnosed glioblastoma. Special emphasis has been given to these imaging technologies as tools to potentially anticipate disease progression, as progression-free survival is frequently used as a surrogate endpoint. METHODS AND MATERIALS: Forty-one patients from a phase II temolozomide clinical trial were included. During follow-up, images were integrated 21 to 28 days after radiochemotherapy and every 2 months thereafter. Assessment of scans included measurement of size of lesion on T1 contrast-enhanced, T2, diffusion, and perfusion images, as well as mass effect. Classical criteria on tumor size variation and clinical parameters were used to set disease progression date. RESULTS: A total of 311 MRI examinations were reviewed. At disease progression (32 patients), a multivariate Cox regression determined 2 significant survival parameters: T1 largest diameter (p < 0.02) and T2 size variation (p < 0.05), whereas perfusion and diffusion were not significant. CONCLUSION: Perfusion and diffusion techniques cannot be used to anticipate tumor progression. Decision making at disease progression is critical, and classical T1 and T2 imaging remain the gold standard. Specifically, a T1 contrast enhancement over 3 cm in largest diameter together with an increased T2 hypersignal is a marker of inferior prognosis.

Apoplastic diffusion barriers in Arabidopsis.

During the development of Arabidopsis and other land plants, diffusion barriers are formed in the apoplast of specialized tissues within a variety of plant organs. While the cuticle of the epidermis is the primary diffusion barrier in the shoot, the Casparian strips and suberin lamellae of the endodermis and the periderm represent the diffusion barriers in the root. Different classes of molecules contribute to the formation of extracellular diffusion barriers in an organ- and tissue-specific manner. Cutin and wax are the major components of the cuticle, lignin forms the early Casparian strip, and suberin is deposited in the stage II endodermis and the periderm. The current status of our understanding of the relationships between the chemical structure, ultrastructure and physiological functions of plant diffusion barriers is discussed. Specific aspects of the synthesis of diffusion barrier components and protocols that can be used for the assessment of barrier function and important barrier properties are also presented.

Histoplasma capsulatum var. duboisii infection in a patient with AIDS: rapid diagnosis using polymerase chain reaction-sequencing.

We describe an original case of disseminated infection with Histoplasma capsulatum (Hc) var. duboisii in an African patient with AIDS who migrated to Switzerland. The diagnosis of histoplasmosis was suggested using direct examination of tissues and confirmed in 24 h with a panfungal polymerase chain reaction assay. The variety duboisii of Hc was established using DNA sequencing of the polymorphic genomic region OLE. Molecular tools allow diagnosis of histoplasmosis in 24 h, which is drastically shorter than culture procedures.

Fick's law adapted to cationic diffusion in a semi-infinite solid: application to spinel megacrystals

In alkaline lavas, the chemical zoning of megacrystals of spinel is due to the cationic exchange between the latter and the host lava. The application of Fick's law to cationic diffusion profiles allows to calculate the time these crystals have stayed in the lava. Those which are in a chemical equilibrium were in contact with the lava during 20 to 30 days, whereas megacrystals lacking this equilibrium were in contact only for 3 or 4 days. The duration of the rise of an ultrabasic nodule in the volcanic chimney was calculated by applying Stokes' law.

Quantitative Assessment of T1 Relaxation and Diffusion as a Prognostic Tool for Brain Development: A Longitudinal Preliminary Study on Preterm Babies

BACKGROUND: Despite major advances in care of premature infants, survivors exhibit mild cognitive deficits in around 40%. Beside severe intraventricular haemorrhages (IVH) and cystic periventricular leucomalacia (PVL), more subtle patterns such as grade I and II IVH, punctuate WM lesions and diffuse PVL might be linked to the cognitive deficits. Grey matter disease is also recognized to contribute to long-term cognitive impairment.¦OBJECTIVE: We intend to use novel MR techniques to study more precisely the different injury patterns. In particular MP2RAGE (magnetization prepared dual rapid echo gradient) produces high-resolution quantitative T1 relaxation maps. This contrast is known to reflect tissue anomalies such as white matter injury in general and dysmyelination in particular. We also used diffusion tensor imaging, a quantitative technique known to reflect white matter maturation and disease.¦DESIGN/METHODS: All preterm infants born under 30 weeks of GA were included. Serial 3T MR-imaging using a neonatal head-coil at DOL 3, 10 and at term equivalent age (TEA), using DTI and MP2RAGE sequences was performed. MP2RAGE generates a T1 map and allows calculating the relaxation time T1. Multiple measurements were performed for each exam in 12 defined white and grey matter ROIs.¦RESULTS: 16 patients were recruited: mean GA 27 2/7 w (191,2d SD±10,8), mean BW 999g (SD±265). 39 MRIs were realized (12 early: mean 4,83d±1,75, 13 late: mean 18,77d±8,05 and 14 at TEA: 88,91d±8,96). Measures of relaxation time T1 show a gradual and significant decrease over time (for ROI PLIC mean±SD in ms: 2100.53±102,75, 2116,5±41,55 and 1726,42±51,31 and for ROI central WM: 2302,25±79,02, 2315,02±115,02 and 1992,7±96,37 for early, late and TEA MR respectively). These trends are also observed in grey matter area, especially in thalamus. Measurements of ADC values show similar monotonous decrease over time.¦CONCLUSIONS: From these preliminary results, we conclude that quantitative MR imaging in very preterm infants is feasible. On the successive MP2RAGE and DTI sequences, we observe a gradual decrease over time in the described ROIs, representing the progressive maturation of the WM micro-structure and interestingly the same evolution is observed in the grey matter. We speculate that our study will provide normative values for T1map and ADC and might be a predictive factor for favourable or less favourable outcome.

Comparative testing of a miniature diffusion size classifier to assess airborne ultrafine particles under field conditions

Miniature diffusion size classifiers (miniDiSC) are novel handheld devices to measure ultrafine particles (UFP). UFP have been linked to the development of cardiovascular and pulmonary diseases; thus, detection and quantification of these particles are important for evaluating their potential health hazards. As part of the UFP exposure assessments of highwaymaintenance workers in western Switzerland, we compared a miniDiSC with a portable condensation particle counter (P-TRAK). In addition, we performed stationary measurements with a miniDiSC and a scanning mobility particle sizer (SMPS) at a site immediately adjacent to a highway. Measurements with miniDiSC and P-TRAK correlated well (correlation of r = 0.84) but average particle numbers of the miniDiSC were 30%âeuro"60% higher. This difference was significantly increased for mean particle diameters below 40 nm. The correlation between theminiDiSC and the SMPSduring stationary measurements was very high (r = 0.98) although particle numbers from the miniDiSC were 30% lower. Differences between the three devices were attributed to the different cutoff diameters for detection. Correction for this size dependent effect led to very similar results across all counters.We did not observe any significant influence of other particle characteristics. Our results suggest that the miniDiSC provides accurate particle number concentrations and geometric mean diameters at traffic-influenced sites, making it a useful tool for personal exposure assessment in such settings.

Imagerie de diffusion hépatique : facteurs prédictifs du « T2 shine-through effect » dans l'hémangiome hépatique.

Objectifs: Déterminer la fréquence et les facteurs prédictifs de l'effet T2 shine-through (T2st) dans l'hémangiome hépatique (HH). Matériels et méthodes: Entre janvier 2010 et novembre 2011, l'imagerie par résonance magnétique (IRM) du foie de 149 patients avec 400 HH a été revue rétrospectivement. Les caractéristiques lésionnelles : taille, localisation, signal et aspect en T1, T2 et diffusion, T2st, coefficient apparent de diffusion de l'HH et du foie (ADChh et ADCf) et type de rehaussement ont été évalués. Résultats: Le T2st était observé dans 53 % des HH. Sa présence était corrélée positivement avec la taille (p=0,046) et négativement avec ADChh et ADCf (p<0,0001, p=0,021). Le T2st était plus fréquent dans le lobe gauche vs droit (p=0,038), et dans les HH typiques (hypersignal T2 et rehaussement en mottes, p=0,0043). L'analyse multivariée retrouvait comme facteurs indépendants de la présence d'un T2st : ADChh et le type de rehaussement. Conclusion: Le T2st est fréquemment observé dans les HH et notamment les formes typiques. Sa présence ne remet pas en question le diagnostic dans les formes typiques.

Taking "Galton's problem" Seriously : Towards a Theory of Policy Diffusion

This article builds on the recent policy diffusion literature and attempts to overcome one of its major problems, namely the lack of a coherent theoretical framework. The literature defines policy diffusion as a process where policy choices are interdependent, and identifies several diffusion mechanisms that specify the link between the policy choices of the various actors. As these mechanisms are grounded in different theories, theoretical accounts of diffusion currently have little internal coherence. In this article we put forward an expected-utility model of policy change that is able to subsume all the diffusion mechanisms. We argue that the expected utility of a policy depends on both its effectiveness and the payoffs it yields, and we show that the various diffusion mechanisms operate by altering these two parameters. Each mechanism affects one of the two parameters, and does so in distinct ways. To account for aggregate patterns of diffusion, we embed our model in a simple threshold model of diffusion. Given the high complexity of the process that results, strong analytical conclusions on aggregate patterns cannot be drawn without more extensive analysis which is beyond the scope of this article. However, preliminary considerations indicate that a wide range of diffusion processes may exist and that convergence is only one possible outcome.

Plasticity of lifespan: a reaction norm perspective.

It is a well-appreciated fact that in many organisms the process of ageing reacts highly plastically, so that lifespan increases or decreases when the environment changes. The perhaps best-known example of such lifespan plasticity is dietary restriction (DR), a phenomenon whereby reduced food intake without malnutrition extends lifespan (typically at the expense of reduced fecundity) and which has been documented in numerous species, from invertebrates to mammals. For the evolutionary biologist, DR and other cases of lifespan plasticity are examples of a more general phenomenon called phenotypic plasticity, the ability of a single genotype to produce different phenotypes (e.g. lifespan) in response to changes in the environment (e.g. changes in diet). To analyse phenotypic plasticity, evolutionary biologists (and epidemiologists) often use a conceptual and statistical framework based on reaction norms (genotype-specific response curves) and genotype × environment interactions (G × E; differences in the plastic response among genotypes), concepts that biologists who are working on molecular aspects of ageing are usually not familiar with. Here I briefly discuss what has been learned about lifespan plasticity or, more generally, about plasticity of somatic maintenance and survival ability. In particular, I argue that adopting the conceptual framework of reaction norms and G × E interactions, as used by evolutionary biologists, is crucially important for our understanding of the mechanisms underlying DR and other forms of lifespan or survival plasticity.

A receptor-like kinase mutant with absent endodermal diffusion barrier displays selective nutrient homeostasis defects.

The endodermis represents the main barrier to extracellular diffusion in plant roots, and it is central to current models of plant nutrient uptake. Despite this, little is known about the genes setting up this endodermal barrier. In this study, we report the identification and characterization of a strong barrier mutant, schengen3 (sgn3). We observe a surprising ability of the mutant to maintain nutrient homeostasis, but demonstrate a major defect in maintaining sufficient levels of the macronutrient potassium. We show that SGN3/GASSHO1 is a receptor-like kinase that is necessary for localizing CASPARIAN STRIP DOMAIN PROTEINS (CASPs)--major players of endodermal differentiation--into an uninterrupted, ring-like domain. SGN3 appears to localize into a broader band, embedding growing CASP microdomains. The discovery of SGN3 strongly advances our ability to interrogate mechanisms of plant nutrient homeostasis and provides a novel actor for localized microdomain formation at the endodermal plasma membrane.

Schizophrenia connectivity: correlation between cognitive deficits and reduced thalamo-cortical fibers

Introduction: Schizophrenia is associated with multiple neuropsychological dysfunctions, such as disturbances of attention, memory, perceptual functioning, concept formation and executive processes. These cognitive functions are reported to depend on the integrity of the prefrontal and thalamo-prefrontal circuits. Multiple lines of evidence suggest that schizophrenia is related to abnormalities in neural circuitry and impaired structural connectivity. Here, we report a preliminary case-control study that showed a correlation between thalamo-frontal connections and several cognitive functions known to be impaired in schizophrenia. Materials and Methods: We investigated 9 schizophrenic patients (DSM IV criteria, Diagnostic Interview for Genetic Studies) and 9 age and sex matched control subjects. We obtained from each volunteer a DT-MRI dataset (3 T, _ _ 1,000 s/mm2), and a high resolution anatomic T1. The thalamo- frontal tracts are simulated with DTI tractography on these dataset, a method allowing inference of the main neural fiber tracks from Diffusion MRI data. In order to see an eventual correlation with the thalamo-frontal connections, every subject performs a battery of neuropsychological tests including computerized tests of attention (sustained attention, selective attention and reaction time), working memory tests (Plane test and the working memory sub-tests of the Wechsler Adult Intelligence Scale), a executive functioning task (Tower of Hanoï) and a test of visual binding abilities. Results: In a pilot case-control study (patients: n _ 9; controls: n _ 9), we showed that this methodology is appropriate and giving results in the excepted range. Considering the relation of the connectivity density and the neuropsychological data, a correlation between the number of thalamo- frontal fibers and the performance in the Tower of Hanoï was observed in the patients (Pearson correlation, r _ 0.76, p _ 0.05) but not in control subjects. In the most difficult item of the test, the least number of fibers corresponds to the worst performance of the test (fig. 2, number of supplementary movements of the elements necessary to realize the right configuration). It's interesting to note here that in an independent study, we showed that schizophrenia patients (n _ 32) perform in the most difficult item of the Tower of Hanoï (Mann-Whitney, p _ 0.005) significantly worse than control subjects (n _ 29). This has been observed in several others neuropsychological studies. Discussion: This pilot study of schizophrenia patients shows a correlation between the number of thalam-frontal fibers and the performance in the Tower of Hanoï, which is a planning and goal oriented actions task known to be associated with frontal dysfonction. This observation is consistent with the proposed impaired connectivity in schizophrenia. We aim to pursue the study with a larger sample in order to determine if other neuropsychological tests may be associated with the connectivity density.

Diffusion-weighted spectroscopy: a novel approach to determine macromolecule resonances in short-echo time 1H-MRS.

Quantification of short-echo time proton magnetic resonance spectroscopy results in >18 metabolite concentrations (neurochemical profile). Their quantification accuracy depends on the assessment of the contribution of macromolecule (MM) resonances, previously experimentally achieved by exploiting the several fold difference in T(1). To minimize effects of heterogeneities in metabolites T(1), the aim of the study was to assess MM signal contributions by combining inversion recovery (IR) and diffusion-weighted proton spectroscopy at high-magnetic field (14.1 T) and short echo time (= 8 msec) in the rat brain. IR combined with diffusion weighting experiments (with δ/Δ = 1.5/200 msec and b-value = 11.8 msec/μm(2)) showed that the metabolite nulled spectrum (inversion time = 740 msec) was affected by residuals attributed to creatine, inositol, taurine, choline, N-acetylaspartate as well as glutamine and glutamate. While the metabolite residuals were significantly attenuated by 50%, the MM signals were almost not affected (< 8%). The combination of metabolite-nulled IR spectra with diffusion weighting allows a specific characterization of MM resonances with minimal metabolite signal contributions and is expected to lead to a more precise quantification of the neurochemical profile.