Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease.

Multi-centre data repositories like the Alzheimer's Disease Neuroimaging Initiative (ADNI) offer a unique research platform, but pose questions concerning comparability of results when using a range of imaging protocols and data processing algorithms. The variability is mainly due to the non-quantitative character of the widely used structural T1-weighted magnetic resonance (MR) images. Although the stability of the main effect of Alzheimer's disease (AD) on brain structure across platforms and field strength has been addressed in previous studies using multi-site MR images, there are only sparse empirically-based recommendations for processing and analysis of pooled multi-centre structural MR data acquired at different magnetic field strengths (MFS). Aiming to minimise potential systematic bias when using ADNI data we investigate the specific contributions of spatial registration strategies and the impact of MFS on voxel-based morphometry in AD. We perform a whole-brain analysis within the framework of Statistical Parametric Mapping, testing for main effects of various diffeomorphic spatial registration strategies, of MFS and their interaction with disease status. Beyond the confirmation of medial temporal lobe volume loss in AD, we detect a significant impact of spatial registration strategy on estimation of AD related atrophy. Additionally, we report a significant effect of MFS on the assessment of brain anatomy (i) in the cerebellum, (ii) the precentral gyrus and (iii) the thalamus bilaterally, showing no interaction with the disease status. We provide empirical evidence in support of pooling data in multi-centre VBM studies irrespective of disease status or MFS.

Cerebellar cortical layers: in vivo visualization with structural high-field-strength MR imaging.

Purpose: To perform in vivo imaging of the cerebellum with an in-plane resolution of 120 mm to observe its cortical granular and molecular layers by taking advantage of the high signal-to-noise ratio and the increased magnetic susceptibility-related contrast available at high magnetic field strength such as 7 T. Materials and Methods: The study was approved by the institutional review board, and all patients provided written consent. Three healthy persons (two men, one woman; mean age, 30 years; age range, 28-31 years) underwent MR imaging with a 7-T system. Gradient-echo images (repetition time msec/echo time msec, 1000/25) of the human cerebellum were acquired with a nominal in-plane resolution of approximately 120 mum and a section thickness of 1 mm. Results: Structures with dimensions as small as 240 mum, such as the granular and molecular layers in the cerebellar cortex, were detected in vivo. The detection of these structures was confirmed by comparing the contrast obtained on T2*-weighted and phase images with that obtained on images of rat cerebellum acquired at 14 T with 30 mum in-plane resolution. Conclusion: In vivo cerebellar imaging at near-microscopic resolution is feasible at 7 T. Such detailed observation of an anatomic area that can be affected by a number of neurologic and psychiatric diseases, such as stroke, tumors, autism, and schizophrenia, could potentially provide newer markers for diagnosis and follow-up in patients with such pathologic conditions. (c) RSNA, 2010.

Evaluating effects of spectral training data distribution on continuous field mapping performance

Continuous field mapping has to address two conflicting remote sensing requirements when collecting training data. On one hand, continuous field mapping trains fractional land cover and thus favours mixed training pixels. On the other hand, the spectral signature has to be preferably distinct and thus favours pure training pixels. The aim of this study was to evaluate the sensitivity of training data distribution along fractional and spectral gradients on the resulting mapping performance. We derived four continuous fields (tree, shrubherb, bare, water) from aerial photographs as response variables and processed corresponding spectral signatures from multitemporal Landsat 5 TM data as explanatory variables. Subsequent controlled experiments along fractional cover gradients were then based on generalised linear models. Resulting fractional and spectral distribution differed between single continuous fields, but could be satisfactorily trained and mapped. Pixels with fractional or without respective cover were much more critical than pure full cover pixels. Error distribution of continuous field models was non-uniform with respect to horizontal and vertical spatial distribution of target fields. We conclude that a sampling for continuous field training data should be based on extent and densities in the fractional and spectral, rather than the real spatial space. Consequently, adequate training plots are most probably not systematically distributed in the real spatial space, but cover the gradient and covariate structure of the fractional and spectral space well. (C) 2009 International Society for Photogrammetry and Remote Sensing, Inc. (ISPRS). Published by Elsevier B.V. All rights reserved.

Accuracy of out-of-field dose calculation of tomotherapy and cyberknife treatment planning systems: A dosimetric study.

PURPOSE: Late toxicities such as second cancer induction become more important as treatment outcome improves. Often the dose distribution calculated with a commercial treatment planning system (TPS) is used to estimate radiation carcinogenesis for the radiotherapy patient. However, for locations beyond the treatment field borders, the accuracy is not well known. The aim of this study was to perform detailed out-of-field-measurements for a typical radiotherapy treatment plan administered with a Cyberknife and a Tomotherapy machine and to compare the measurements to the predictions of the TPS. MATERIALS AND METHODS: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The measured dose distributions from 6 MV intensity-modulated treatment beams for CyberKnife and TomoTherapy machines were compared to the dose calculations from the TPS. RESULTS: The TPS are underestimating the dose far away from the target volume. Quantitatively the Cyberknife underestimates the dose at 40cm from the PTV border by a factor of 60, the Tomotherapy TPS by a factor of two. If a 50% dose uncertainty is accepted, the Cyberknife TPS can predict doses down to approximately 10 mGy/treatment Gy, the Tomotherapy-TPS down to 0.75 mGy/treatment Gy. The Cyberknife TPS can then be used up to 10cm from the PTV border the Tomotherapy up to 35cm. CONCLUSIONS: We determined that the Cyberknife and Tomotherapy TPS underestimate substantially the doses far away from the treated volume. It is recommended not to use out-of-field doses from the Cyberknife TPS for applications like modeling of second cancer induction. The Tomotherapy TPS can be used up to 35cm from the PTV border (for a 390 cm(3) large PTV).

Polyethylene wear in anatomic and reversed shoulder prostheses

Purpose: Polyethylene wear is a recurrent problem in joint arthroplasty. Small debris particles are also associated to inflammation reaction of the surrounding bone, eventually leading to the failure of the bound between the implant and the host bone, and implant loosening. The goal of this study was thus to estimate the volume of polyethylene wear of a reversed prosthesis, and compare it to an anatomic prosthesis, during one year of activities of daily living. Material and Methods: A numerical musculoskeletal model of the glenohumeral joint was used for this comparative study. The reversed (RP) and anatomic (AP) Aequalis prostheses were positioned in the numerical model. Eight levels of abduction were considered. Their daily frequency was estimated from in-vivo recorded data on healthy volunteers during activities of daily living. One year of use was simulated to predict the linear and volumetric wear. The volumetric wear was the difference of volume between the original and worn component. Results: With the AP, the contact pattern on the glenoid surface moved rapidly from the inferior to the superior side during the first 30 degrees of abduction, and then went back to the inferior side. With the RP, the contact pattern on the humeral cup surface remained at the inferior side. Contact pressure was 20 times lower with the RP than with the AP. One year of use produced a maximum linear wear of 0.2 mm with the AP, and 0.13 mm with the RP. However, the volumetric wear was 8.4 mm3 with the AP, but reached 44.6 mm3 with the RP. Conclusion: Polyethylene particles are a matter of concern with AP. Infiltration of these particles within the bone-implant interface can induce a implant loosening. This problem should not be underestimated with RP. It might be associated to a higher level of humeral stem loosening reported with RP. The long term survival of RP might be improved by using a highly cross-linked polyethylene, which has a better abrasion resistance but lower plastic resistance.

A new self-expanding aortic stent valve with annular fixation: in vitro haemodynamic assessment.

OBJECTIVE: Balloon-expandable stent valves require flow reduction during implantation (rapid pacing). The present study was designed to compare a self-expanding stent valve with annular fixation versus a balloon-expandable stent valve. METHODS: Implantation of a new self-expanding stent valve with annular fixation (Symetis, Lausanne, Switzerland) was assessed versus balloon-expandable stent valve, in a modified Dynatek Dalta pulse duplicator (sealed port access to the ventricle for transapical route simulation), interfaced with a computer for digital readout, carrying a 25 mm porcine aortic valve. The cardiovascular simulator was programmed to mimic an elderly woman with aortic stenosis: 120/85 mmHg aortic pressure, 60 strokes/min (66.5 ml), 35% systole (2.8 l/min). RESULTS: A total of 450 cardiac cycles was analysed. Stepwise expansion of the self-expanding stent valve with annular fixation (balloon-expandable stent valve) resulted in systolic ventricular increase from 120 to 121 mmHg (126 to 830+/-76 mmHg)*, and left ventricular outflow obstruction with mean transvalvular gradient of 11+/-1.5 mmHg (366+/-202 mmHg)*, systolic aortic pressure dropped distal to the valve from 121 to 64.5+/-2 mmHg (123 to 55+/-30 mmHg) N.S., and output collapsed to 1.9+/-0.06 l/min (0.71+/-0.37 l/min* (before complete obstruction)). No valve migration occurred in either group. (*=p<0.05). CONCLUSIONS: Implantation of this new self-expanding stent valve with annular fixation has little impact on haemodynamics and has the potential for working heart implantation in vivo. Flow reduction (rapid pacing) is not necessary.

BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination.

The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.

The data treatment dependent variability of U-Pb zircon ages obtained using mono-collector, sector field, laser ablation ICP-MS

U-Pb dating of zircons by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) is a widely used analytical technique in Earth Sciences. For U-Pb ages below 1 billion years (1 Ga), Pb-206/U-238 dates are usually used, showing the least bias by external parameters such as the presence of initial lead and its isotopic composition in the analysed mineral. Precision and accuracy of the Pb/U ratio are thus of highest importance in LA-ICPMS geochronology. We consider the evaluation of the statistical distribution of the sweep intensities based on goodness-of-fit tests in order to find a model probability distribution fitting the data to apply an appropriate formulation for the standard deviation. We then discuss three main methods to calculate the Pb/U intensity ratio and its uncertainty in the LA-ICPMS: (1) ratio-of-the-mean intensities method, (2) mean-of-the-intensity-ratios method and (3) intercept method. These methods apply different functions to the same raw intensity vs. time data to calculate the mean Pb/U intensity ratio. Thus, the calculated intensity ratio and its uncertainty depend on the method applied. We demonstrate that the accuracy and, conditionally, the precision of the ratio-of-the-mean intensities method are invariant to the intensity fluctuations and averaging related to the dwell time selection and off-line data transformation (averaging of several sweeps); we present a statistical approach how to calculate the uncertainty of this method for transient signals. We also show that the accuracy of methods (2) and (3) is influenced by the intensity fluctuations and averaging, and the extent of this influence can amount to tens of percentage points; we show that the uncertainty of these methods also depends on how the signal is averaged. Each of the above methods imposes requirements to the instrumentation. The ratio-of-the-mean intensities method is sufficiently accurate provided the laser induced fractionation between the beginning and the end of the signal is kept low and linear. We show, based on a comprehensive series of analyses with different ablation pit sizes, energy densities and repetition rates for a 193 nm ns-ablation system that such a fractionation behaviour requires using a low ablation speed (low energy density and low repetition rate). Overall, we conclude that the ratio-of-the-mean intensities method combined with low sampling rates is the most mathematically accurate among the existing data treatment methods for U-Pb zircon dating by sensitive sector field ICPMS.

Multiscale assessment of plant diversity in wooded pastures of the Jura mountains

Résumé La diminution de la biodiversité, à toutes les échelles spatiales et sur l'ensemble de la planète, compte parmi les problèmes les plus préoccupants de notre époque. En terme de conservation, il est aujourd'hui primordial de mieux comprendre les mécanismes qui créent et maintiennent la biodiversité dans les écosystèmes naturels ou anthropiques. La présente étude a pour principal objectif d'améliorer notre compréhension des patrons de biodiversité végétale et des mécanismes sous jacents, dans un écosystème complexe, riche en espèces et à forte valeur patrimoniale, les pâturages boisés jurassiens. Structure et échelle spatiales sont progressivement reconnues comme des dimensions incontournables dans l'étude des patrons de biodiversité. De plus, ces deux éléments jouent un rôle central dans plusieurs théories écologiques. Toutefois, peu d'hypothèses issues de simulations ou d'études théoriques concernant le lien entre structure spatiale du paysage et biodiversité ont été testées de façon empirique. De même, l'influence des différentes composantes de l'échelle spatiale sur les patrons de biodiversité est méconnue. Cette étude vise donc à tester quelques-unes de ces hypothèses et à explorer les patrons spatiaux de biodiversité dans un contexte multi-échelle, pour différentes mesures de biodiversité (richesse et composition en espèces) à l'aide de données de terrain. Ces données ont été collectées selon un plan d'échantillonnage hiérarchique. Dans un premier temps, nous avons testé l'hypothèse élémentaire selon laquelle la richesse spécifique (le nombre d'espèces sur une surface donnée) est liée à l'hétérogénéité environnementale quelque soit l'échelle. Nous avons décomposé l'hétérogénéité environnementale en deux parties, la variabilité des conditions environnementales et sa configuration spatiale. Nous avons montré que, en général, la richesse spécifique augmentait avec l'hétérogénéité de l'environnement : elle augmentait avec le nombre de types d'habitats et diminuait avec l'agrégation spatiale de ces habitats. Ces effets ont été observés à toutes les échelles mais leur nature variait en fonction de l'échelle, suggérant une modification des mécanismes. Dans un deuxième temps, la structure spatiale de la composition en espèces a été décomposée en relation avec 20 variables environnementales et 11 traits d'espèces. Nous avons utilisé la technique de partition de la variation et un descripteur spatial, récemment développé, donnant accès à une large gamme d'échelles spatiales. Nos résultats ont montré que la structure spatiale de la composition en espèces végétales était principalement liée à la topographie, aux échelles les plus grossières, et à la disponibilité en lumière, aux échelles les plus fines. La fraction non-environnementale de la variation spatiale de la composition spécifique avait une relation complexe avec plusieurs traits d'espèces suggérant un lien avec des processus biologiques tels que la dispersion, dépendant de l'échelle spatiale. Dans un dernier temps, nous avons testé, à plusieurs échelles spatiales, les relations entre trois composantes de la biodiversité : la richesse spécifique totale d'un échantillon (diversité gamma), la richesse spécifique moyenne (diversité alpha), mesurée sur des sous-échantillons, et les différences de composition spécifique entre les sous-échantillons (diversité beta). Les relations deux à deux entre les diversités alpha, beta et gamma ne suivaient pas les relations attendues, tout du moins à certaines échelles spatiales. Plusieurs de ces relations étaient fortement dépendantes de l'échelle. Nos résultats ont mis en évidence l'importance du rapport d'échelle (rapport entre la taille de l'échantillon et du sous-échantillon) lors de l'étude des patrons spatiaux de biodiversité. Ainsi, cette étude offre un nouvel aperçu des patrons spatiaux de biodiversité végétale et des mécanismes potentiels permettant la coexistence des espèces. Nos résultats suggèrent que les patrons de biodiversité ne peuvent être expliqués par une seule théorie, mais plutôt par une combinaison de théories. Ils ont également mis en évidence le rôle essentiel joué par la structure spatiale dans la détermination de la biodiversité, quelque soit le composant de la biodiversité considéré. Enfin, cette étude souligne l'importance de prendre en compte plusieurs échelles spatiales et différents constituants de l'échelle spatiale pour toute étude relative à la diversité spécifique. Abstract The world-wide loss of biodiversity at all scales has become a matter of urgent concern, and improving our understanding of local drivers of biodiversity in natural and anthropogenic ecosystems is now crucial for conservation. The main objective of this study was to further our comprehension of the driving forces controlling biodiversity patterns in a complex and diverse ecosystem of high conservation value, wooded pastures. Spatial pattern and scale are central to several ecological theories, and it is increasingly recognized that they must be taken -into consideration when studying biodiversity patterns. However, few hypotheses developed from simulations or theoretical studies have been tested using field data, and the evolution of biodiversity patterns with different scale components remains largely unknown. We test several such hypotheses and explore spatial patterns of biodiversity in a multi-scale context and using different measures of biodiversity (species richness and composition), with field data. Data were collected using a hierarchical sampling design. We first tested the simple hypothesis that species richness, the number of species in a given area, is related to environmental heterogeneity at all scales. We decomposed environmental heterogeneity into two parts: the variability of environmental conditions and its spatial configuration. We showed that species richness generally increased with environmental heterogeneity: species richness increased with increasing number of habitat types and with decreasing spatial aggregation of those habitats. Effects occurred at all scales but the nature of the effect changed with scale, suggesting a change in underlying mechanisms. We then decomposed the spatial structure of species composition in relation to environmental variables and species traits using variation partitioning and a recently developed spatial descriptor, allowing us to capture a wide range of spatial scales. We showed that the spatial structure of plant species composition was related to topography at the coarsest scales and insolation at finer scales. The non-environmental fraction of the spatial variation in species composition had a complex relationship with several species traits, suggesting a scale-dependent link to biological processes, particularly dispersal. Finally, we tested, at different spatial scales, the relationships between different components of biodiversity: total sample species richness (gamma diversity), mean species .richness (alpha diversity), measured in nested subsamples, and differences in species composition between subsamples (beta diversity). The pairwise relationships between alpha, beta and gamma diversity did not follow the expected patterns, at least at certain scales. Our result indicated a strong scale-dependency of several relationships, and highlighted the importance of the scale ratio when studying biodiversity patterns. Thus, our results bring new insights on the spatial patterns of biodiversity and the possible mechanisms allowing species coexistence. They suggest that biodiversity patterns cannot be explained by any single theory proposed in the literature, but a combination of theories is sufficient. Spatial structure plays a crucial role for all components of biodiversity. Results emphasize the importance of considering multiple spatial scales and multiple scale components when studying species diversity.

Active deformation fields: dense deformation field estimation for atlas-based segmentation using the active contour framework.

This paper presents a new and original variational framework for atlas-based segmentation. The proposed framework integrates both the active contour framework, and the dense deformation fields of optical flow framework. This framework is quite general and encompasses many of the state-of-the-art atlas-based segmentation methods. It also allows to perform the registration of atlas and target images based on only selected structures of interest. The versatility and potentiality of the proposed framework are demonstrated by presenting three diverse applications: In the first application, we show how the proposed framework can be used to simulate the growth of inconsistent structures like a tumor in an atlas. In the second application, we estimate the position of nonvisible brain structures based on the surrounding structures and validate the results by comparing with other methods. In the final application, we present the segmentation of lymph nodes in the Head and Neck CT images, and demonstrate how multiple registration forces can be used in this framework in an hierarchical manner.