Coronary MR imaging using free-breathing 3D steady-state free precession with radial k-space sampling.

PURPOSE: To investigate the potential of free-breathing 3D steady-state free precession (SSFP) imaging with radial k-space sampling for coronary MR-angiography (MRA), coronary projection MR-angiography and coronary vessel wall imaging. MATERIALS AND METHODS: A navigator-gated free-breathing T2-prepared 3D SSFP sequence (TR = 6.1 ms, TE = 3.0 ms, flip angle = 120 degrees, field-of-view = 360 mm(2)) with radial k-space sampling (384 radials) was implemented for coronary MRA. For projection coronary MRA, this sequence was combined with a 2D selective aortic spin tagging pulse. Coronary vessel wall imaging was performed using a high-resolution inversion-recovery black-blood 3D radial SSFP sequence (384 radials, TR = 5.3 ms, TE = 2.7 ms, flip angle = 55 degrees, reconstructed resolution 0.35 x 0.35 x 1.2 mm(3)) and a local re-inversion pulse. Six healthy volunteers (two for each sequence) were investigated. Motion artifact level was assessed by two radiologists. Results: In coronary MRA, the coronary lumen was displayed with a high signal and high contrast to the surrounding lumen. Projection coronary MRA demonstrated selective visualization of the coronary lumen while surrounding tissue was almost completely suppressed. In coronary vessel wall imaging, the vessel wall was displayed with a high signal when compared to the blood pool and the surrounding tissue. No visible motion artifacts were seen. Conclusion: 3D radial SSFP imaging enables coronary MRA, coronary projection MRA and coronary vessel wall imaging with a low motion artifact level.

Inversion of crosshole seismic data in heterogenous environments : Comparison of waveform and ray-based approaches

High-resolution tomographic imaging of the shallow subsurface is becoming increasingly important for a wide range of environmental, hydrological and engineering applications. Because of their superior resolution power, their sensitivity to pertinent petrophysical parameters, and their far reaching complementarities, both seismic and georadar crosshole imaging are of particular importance. To date, corresponding approaches have largely relied on asymptotic, ray-based approaches, which only account for a very small part of the observed wavefields, inherently suffer from a limited resolution, and in complex environments may prove to be inadequate. These problems can potentially be alleviated through waveform inversion. We have developed an acoustic waveform inversion approach for crosshole seismic data whose kernel is based on a finite-difference time-domain (FDTD) solution of the 2-D acoustic wave equations. This algorithm is tested on and applied to synthetic data from seismic velocity models of increasing complexity and realism and the results are compared to those obtained using state-of-the-art ray-based traveltime tomography. Regardless of the heterogeneity of the underlying models, the waveform inversion approach has the potential of reliably resolving both the geometry and the acoustic properties of features of the size of less than half a dominant wavelength. Our results do, however, also indicate that, within their inherent resolution limits, ray-based approaches provide an effective and efficient means to obtain satisfactory tomographic reconstructions of the seismic velocity structure in the presence of mild to moderate heterogeneity and in absence of strong scattering. Conversely, the excess effort of waveform inversion provides the greatest benefits for the most heterogeneous, and arguably most realistic, environments where multiple scattering effects tend to be prevalent and ray-based methods lose most of their effectiveness.

Effect of the September 11, 2001 terrorist attack on a state highway patrol trooper's heart rate variability

BACKGROUND: On September 11, 2001, terrorists attacked the United States. By coincidence, a North Carolina highway patrol trooper was wearing an ambulatory ECG Holter monitor at this time as part of an air pollution study. METHODS: Heart rate variability parameters were analyzed: standard deviation of normal to normal beat intervals (SDNN) and percentage of interval differences >50 ms (PNN50). RESULTS: The trooper's heart rate variability changed immediately after learning about the terrorist attacks. Heart rate increased and PNN50 decreased, while SDNN increased strongly. CONCLUSIONS: These changes suggest strong emotional sympathetic stress associated with parasympathetic withdrawal in response to the news about the terrorist attack. [Authors]

Effects of phylogenetic signal on ancestral state reconstruction.

One of the standard tools used to understand the processes shaping trait evolution along the branches of a phylogenetic tree is the reconstruction of ancestral states (Pagel 1999). The purpose is to estimate the values of the trait of interest for every internal node of a phylogenetic tree based on the trait values of the extant species, a topology and, depending on the method used, branch lengths and a model of trait evolution (Ronquist 2004). This approach has been used in a variety of contexts such as biogeography (e.g., Nepokroeff et al. 2003, Blackburn 2008), ecological niche evolution (e.g., Smith and Beaulieu 2009, Evans et al. 2009) and metabolic pathway evolution (e.g., Gabaldón 2003, Christin et al. 2008). Investigations of the factors affecting the accuracy with which ancestral character states can be reconstructed have focused in particular on the choice of statistical framework (Ekman et al. 2008) and the selection of the best model of evolution (Cunningham et al. 1998, Mooers et al. 1999). However, other potential biases affecting these methods, such as the effect of tree shape (Mooers 2004), taxon sampling (Salisbury and Kim 2001) as well as reconstructing traits involved in species diversification (Goldberg and Igić 2008), have also received specific attention. Most of these studies conclude that ancestral character states reconstruction is still not perfect, and that further developments are necessary to improve its accuracy (e.g., Christin et al. 2010). Here, we examine how different estimations of branch lengths affect the accuracy of ancestral character state reconstruction. In particular, we tested the effect of using time-calibrated versus molecular branch lengths and provide guidelines to select the most appropriate branch lengths to reconstruct the ancestral state of a trait.

Antiepileptika bei Frauen im gebärfähigen Alter und in der Schwangerschaft : Vergleich der Fachinformationen in Deutschland und der Schweiz mit dem aktuellen Wissensstand [Antiepileptics in women of childbearing age and during pregnancy : Comparison of specialized information with the current state of knowledge in Germany and Switzerland].

BACKGROUND: Healthcare professionals regularly read the summary of product characteristics (SmPC) as one of the various sources of information on the risks of drug use in women of childbearing age and during pregnancy. The aim of this article is to present an overview of the teratogenic potential of various antiepileptic drugs and to compare these data with the information provided by the SmPCs. METHODS: A literature search on the teratogenic risks of 19 antiepileptic agents was conducted and the results were compared with the information on the use in women of childbearing age and during pregnancy provided by the SmPCs of 38 commercial products available in Switzerland and Germany. RESULTS: The teratogenic risk is discussed in all available SmPCs. Quantification of the risk for birth defects and the numbers of documented pregnancies are mostly missing. Reproductive safety information in SmPCs showed poor concordance with risk levels reported in the literature. Recommendations concerning the need to monitor plasma levels and possibly perform dose adjustments during pregnancy to prevent treatment failure were missing in five Swiss and two German SmPCs. DISCUSSION: The information regarding use in women of childbearing age and during pregnancy provided by the SmPCs is heterogeneous and poorly reflects the current state of knowledge. Regular updates of SmPCs are warranted in order for these documents to be of reliable use for health care professionals.

Transcatheter aortic valve implantation (TAVI): state of the art techniques and future perspectives.

Transcatheter aortic valve therapies are the newest established techniques for the treatment of high risk patients affected by severe symptomatic aortic valve stenosis. The transapical approach requires a left anterolateral mini-thoracotomy, whereas the transfemoral method requires an adequate peripheral vascular access and can be performed fully percutaneously. Alternatively, the trans-subclavian access has been recently proposed as a third promising approach. Depending on the technique, the fine stent-valve positioning can be performed with or without contrast injections. The transapical echo-guided stent-valve implantation without angiography (the Lausanne technique) relies entirely on transoesophageal echocardiogramme imaging for the fine stent-valve positioning and it has been proved that this technique prevents the onset of postoperative contrast-related acute kidney failure. Recent published reports have shown good hospital outcomes and short-term results after transcatheter aortic valve implantation, but there are no proven advantages in using the transfemoral or the transapical technique. In particular, the transapical series have a higher mean logistic Euroscore of 27-35%, a procedural success rate above 95% and a mean 30-day mortality between 7.5 and 17.5%, whereas the transfemoral results show a lower logistic Euroscore of 23-25.5%, a procedural success rate above 90% and a 30-day mortality of 7-10.8%. Nevertheless, further clinical trials and long-term results are mandatory to confirm this positive trend. Future perspectives in transcatheter aortic valve therapies would be the development of intravascular devices for the ablation of the diseased valve leaflets and the launch of new stent-valves with improved haemodynamic, different sizes and smaller delivery systems.

Active learning methods for remote sensing image classification

In this paper, we propose two active learning algorithms for semiautomatic definition of training samples in remote sensing image classification. Based on predefined heuristics, the classifier ranks the unlabeled pixels and automatically chooses those that are considered the most valuable for its improvement. Once the pixels have been selected, the analyst labels them manually and the process is iterated. Starting with a small and nonoptimal training set, the model itself builds the optimal set of samples which minimizes the classification error. We have applied the proposed algorithms to a variety of remote sensing data, including very high resolution and hyperspectral images, using support vector machines. Experimental results confirm the consistency of the methods. The required number of training samples can be reduced to 10% using the methods proposed, reaching the same level of accuracy as larger data sets. A comparison with a state-of-the-art active learning method, margin sampling, is provided, highlighting advantages of the methods proposed. The effect of spatial resolution and separability of the classes on the quality of the selection of pixels is also discussed.

Steady-state equilibrium phase inversion recovery ON-resonant water suppression (IRON) MR angiography in conjunction with superparamagnetic nanoparticles. A robust technique for imaging within a wide range of contrast agent dosages.

PURPOSE: To investigate the ability of inversion recovery ON-resonant water suppression (IRON) in conjunction with P904 (superparamagnetic nanoparticles which consisting of a maghemite core coated with a low-molecular-weight amino-alcohol derivative of glucose) to perform steady-state equilibrium phase MR angiography (MRA) over a wide dose range. MATERIALS AND METHODS: Experiments were approved by the institutional animal care committee. Rabbits (n = 12) were imaged at baseline and serially after the administration of 10 incremental dosages of 0.57-5.7 mgFe/Kg P904. Conventional T1-weighted and IRON MRA were obtained on a clinical 1.5 Tesla (T) scanner to image the thoracic and abdominal aorta, and peripheral vessels. Contrast-to-noise ratios (CNR) and vessel sharpness were quantified. RESULTS: Using IRON MRA, CNR and vessel sharpness progressively increased with incremental dosages of the contrast agent P904, exhibiting constantly higher contrast values than T1 -weighted MRA over a very wide range of contrast agent doses (CNR of 18.8 ± 5.6 for IRON versus 11.1 ± 2.8 for T1 -weighted MRA at 1.71 mgFe/kg, P = 0.02 and 19.8 ± 5.9 for IRON versus -0.8 ± 1.4 for T1-weighted MRA at 3.99 mgFe/kg, P = 0.0002). Similar results were obtained for vessel sharpness in peripheral vessels, (Vessel sharpness of 46.76 ± 6.48% for IRON versus 33.20 ± 3.53% for T1-weighted MRA at 1.71 mgFe/Kg, P = 0.002, and of 48.66 ± 5.50% for IRON versus 19.00 ± 7.41% for T1-weighted MRA at 3.99 mgFe/Kg, P = 0.003). CONCLUSION: Our study suggests that quantitative CNR and vessel sharpness after the injection of P904 are consistently higher for IRON MRA when compared with conventional T1-weighted MRA. These findings apply for a wide range of contrast agent dosages.

The stationary distribution of a continuously varying strategy in a class-structured population under mutation-selection-drift balance.

Many traits and/or strategies expressed by organisms are quantitative phenotypes. Because populations are of finite size and genomes are subject to mutations, these continuously varying phenotypes are under the joint pressure of mutation, natural selection and random genetic drift. This article derives the stationary distribution for such a phenotype under a mutation-selection-drift balance in a class-structured population allowing for demographically varying class sizes and/or changing environmental conditions. The salient feature of the stationary distribution is that it can be entirely characterized in terms of the average size of the gene pool and Hamilton's inclusive fitness effect. The exploration of the phenotypic space varies exponentially with the cumulative inclusive fitness effect over state space, which determines an adaptive landscape. The peaks of the landscapes are those phenotypes that are candidate evolutionary stable strategies and can be determined by standard phenotypic selection gradient methods (e.g. evolutionary game theory, kin selection theory, adaptive dynamics). The curvature of the stationary distribution provides a measure of the stability by convergence of candidate evolutionary stable strategies, and it is evaluated explicitly for two biological scenarios: first, a coordination game, which illustrates that, for a multipeaked adaptive landscape, stochastically stable strategies can be singled out by letting the size of the gene pool grow large; second, a sex-allocation game for diploids and haplo-diploids, which suggests that the equilibrium sex ratio follows a Beta distribution with parameters depending on the features of the genetic system.

Robust volume-targeted balanced steady-state free-precession coronary magnetic resonance angiography in a breathhold at 3.0 Tesla: a reproducibility study.

BACKGROUND: Transient balanced steady-state free-precession (bSSFP) has shown substantial promise for noninvasive assessment of coronary arteries but its utilization at 3.0 T and above has been hampered by susceptibility to field inhomogeneities that degrade image quality. The purpose of this work was to refine, implement, and test a robust, practical single-breathhold bSSFP coronary MRA sequence at 3.0 T and to test the reproducibility of the technique. METHODS: A 3D, volume-targeted, high-resolution bSSFP sequence was implemented. Localized image-based shimming was performed to minimize inhomogeneities of both the static magnetic field and the radio frequency excitation field. Fifteen healthy volunteers and three patients with coronary artery disease underwent examination with the bSSFP sequence (scan time = 20.5 ± 2.0 seconds), and acquisitions were repeated in nine subjects. The images were quantitatively analyzed using a semi-automated software tool, and the repeatability and reproducibility of measurements were determined using regression analysis and intra-class correlation coefficient (ICC), in a blinded manner. RESULTS: The 3D bSSFP sequence provided uniform, high-quality depiction of coronary arteries (n = 20). The average visible vessel length of 100.5 ± 6.3 mm and sharpness of 55 ± 2% compared favorably with earlier reported navigator-gated bSSFP and gradient echo sequences at 3.0 T. Length measurements demonstrated a highly statistically significant degree of inter-observer (r = 0.994, ICC = 0.993), intra-observer (r = 0.894, ICC = 0.896), and inter-scan concordance (r = 0.980, ICC = 0.974). Furthermore, ICC values demonstrated excellent intra-observer, inter-observer, and inter-scan agreement for vessel diameter measurements (ICC = 0.987, 0.976, and 0.961, respectively), and vessel sharpness values (ICC = 0.989, 0.938, and 0.904, respectively). CONCLUSIONS: The 3D bSSFP acquisition, using a state-of-the-art MR scanner equipped with recently available technologies such as multi-transmit, 32-channel cardiac coil, and localized B0 and B1+ shimming, allows accelerated and reproducible multi-segment assessment of the major coronary arteries at 3.0 T in a single breathhold. This rapid sequence may be especially useful for functional imaging of the coronaries where the acquisition time is limited by the stress duration and in cases where low navigator-gating efficiency prohibits acquisition of a free breathing scan in a reasonable time period.

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs--liver, lung, skin, brain--are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.

Data-driven clustering : new methods and applications

Abstract : This work is concerned with the development and application of novel unsupervised learning methods, having in mind two target applications: the analysis of forensic case data and the classification of remote sensing images. First, a method based on a symbolic optimization of the inter-sample distance measure is proposed to improve the flexibility of spectral clustering algorithms, and applied to the problem of forensic case data. This distance is optimized using a loss function related to the preservation of neighborhood structure between the input space and the space of principal components, and solutions are found using genetic programming. Results are compared to a variety of state-of--the-art clustering algorithms. Subsequently, a new large-scale clustering method based on a joint optimization of feature extraction and classification is proposed and applied to various databases, including two hyperspectral remote sensing images. The algorithm makes uses of a functional model (e.g., a neural network) for clustering which is trained by stochastic gradient descent. Results indicate that such a technique can easily scale to huge databases, can avoid the so-called out-of-sample problem, and can compete with or even outperform existing clustering algorithms on both artificial data and real remote sensing images. This is verified on small databases as well as very large problems. Résumé : Ce travail de recherche porte sur le développement et l'application de méthodes d'apprentissage dites non supervisées. Les applications visées par ces méthodes sont l'analyse de données forensiques et la classification d'images hyperspectrales en télédétection. Dans un premier temps, une méthodologie de classification non supervisée fondée sur l'optimisation symbolique d'une mesure de distance inter-échantillons est proposée. Cette mesure est obtenue en optimisant une fonction de coût reliée à la préservation de la structure de voisinage d'un point entre l'espace des variables initiales et l'espace des composantes principales. Cette méthode est appliquée à l'analyse de données forensiques et comparée à un éventail de méthodes déjà existantes. En second lieu, une méthode fondée sur une optimisation conjointe des tâches de sélection de variables et de classification est implémentée dans un réseau de neurones et appliquée à diverses bases de données, dont deux images hyperspectrales. Le réseau de neurones est entraîné à l'aide d'un algorithme de gradient stochastique, ce qui rend cette technique applicable à des images de très haute résolution. Les résultats de l'application de cette dernière montrent que l'utilisation d'une telle technique permet de classifier de très grandes bases de données sans difficulté et donne des résultats avantageusement comparables aux méthodes existantes.