Simulation des caractéristiques ECG du syndrome de Brugada à l'aide d'un programme de modélisation 3D

Introduction : Le syndrome de Brugada, décrit en 1992 par Pedro et Josep Brugada, est un syndrome cardiaque caractérisé par un sus-décalage particulier du segment ST associé à un bloc de branche droit atypique au niveau des dérivations ECG V1 à V3. Les altérations ECG du syndrome de Brugada sont classifiées en 3 types dont seul le type 1 est diagnostique. Les mécanismes physiopathologiques exacts de ce syndrome sont pour le moment encore controversés. Plusieurs hypothèses sont proposées dans la littérature dont deux principales retiennent l'attention : 1) le modèle du trouble de repolarisation stipule des potentiels d'action réduits en durée et en amplitude liés à un changement de répartition de canaux potassiques 2) le modèle du trouble de dépolarisation spécifie un retard de conduction se traduisant par une dépolarisation retardée. Dans le STEMI, un sus-décalage ST ressemblant à celui du syndrome de Brugada est expliqué par deux théories : 1) le courant de lésion diastolique suggère une élévation du potentiel diastolique transformé artificiellement en sus-décalage ST par les filtres utilisés dans tous les appareils ECG.¦Objectif : Recréer les manifestations ECG du syndrome de Brugada en appliquant les modifications du potentiel d'action des cardiomyocytes rapportées dans la littérature.¦Méthode : Pour ce travail, nous avons utilisé "ECGsim", un simulateur informatique réaliste d'ECG disponible gratuitement sur www.ecgsim.org. Ce programme est basé sur une reconstruction de l'ECG de surface à l'aide de 1500 noeuds représentant chacun les potentiels d'action des ventricules droit et gauche, épicardiques et endocardiques. L'ECG simulé peut être donc vu comme l'intégration de l'ensemble de ces potentiels d'action en tenant compte des propriétés de conductivité des tissus s'interposant entre les électrodes de surface et le coeur. Dans ce programme, nous avons définit trois zones, de taille différente, comprenant la chambre de chasse du ventricule droit. Pour chaque zone, nous avons reproduit les modifications des potentiels d'action citées dans les modèles du trouble de repolarisation et de dépolarisation et des théories de courant de lésion systolique et diastolique. Nous avons utilisé, en plus des douze dérivations habituelles, une électrode positionnée en V2IC3 (i.e. 3ème espace intercostal) sur le thorax virtuel du programme ECGsim.¦Résultats : Pour des raisons techniques, le modèle du trouble de repolarisation n'a pas pu être entièrement réalisée dans ce travail. Le modèle du trouble de dépolarisation ne reproduit pas d'altération de type Brugada mais un bloc de branche droit plus ou moins complet. Le courant de lésion diastolique permet d'obtenir un sus-décalage ST en augmentant le potentiel diastolique épicardique des cardiomyocytes de la chambre de chasse du ventricule droit. Une inversion de l'onde T apparaît lorsque la durée du potentiel d'action est prolongée. L'amplitude du sus-décalage ST dépend de la valeur du potentiel diastolique, de la taille de la lésion et de sa localisation épicardique ou transmurale. Le courant de lésion systolique n'entraîne pas de sus-décalage ST mais accentue l'amplitude de l'onde T.¦Discussion et conclusion : Dans ce travail, l'élévation du potentiel diastolique avec un prolongement de la durée du potentiel d'action est la combinaison qui reproduit le mieux les altérations ECG du Brugada. Une persistance de cellules de type nodal au niveau de la chambre de chasse du ventricule droit pourrait être une explication à ces modifications particulières du potentiel d'action. Le risque d'arythmie dans la Brugada pourrait également être expliqué par une automaticité anormale des cellules de type nodal. Ainsi, des altérations des mécanismes cellulaires impliqués dans le maintien du potentiel diastolique pourraient être présentes dans le syndrome de Brugada, ce qui, à notre connaissance, n'a jamais été rapporté dans la littérature.

Iterative reconstruction methods in two different MDCT scanners: Physical metrics and 4-alternative forced-choice detectability experiments - A phantom approach.

This paper characterizes and evaluates the potential of three commercial CT iterative reconstruction methods (ASIR?, VEO? and iDose(4 ()?())) for dose reduction and image quality improvement. We measured CT number accuracy, standard deviation (SD), noise power spectrum (NPS) and modulation transfer function (MTF) metrics on Catphan phantom images while five human observers performed four-alternative forced-choice (4AFC) experiments to assess the detectability of low- and high-contrast objects embedded in two pediatric phantoms. Results show that 40% and 100% ASIR as well as iDose(4) levels 3 and 6 do not affect CT number and strongly decrease image noise with relative SD constant in a large range of dose. However, while ASIR produces a shift of the NPS curve apex, less change is observed with iDose(4) with respect to FBP methods. With second-generation iterative reconstruction VEO, physical metrics are even further improved: SD decreased to 70.4% at 0.5 mGy and spatial resolution improved to 37% (MTF(50%)). 4AFC experiments show that few improvements in detection task performance are obtained with ASIR and iDose(4), whereas VEO makes excellent detections possible even at an ultra-low-dose (0.3 mGy), leading to a potential dose reduction of a factor 3 to 7 (67%-86%). In spite of its longer reconstruction time and the fact that clinical studies are still required to complete these results, VEO clearly confirms the tremendous potential of iterative reconstructions for dose reduction in CT and appears to be an important tool for patient follow-up, especially for pediatric patients where cumulative lifetime dose still remains high.

3D Automated Lung Nodule Segmentation in HRCT

A fully-automated 3D image analysis method is proposed to segment lung nodules in HRCT. A specific gray-level mathematical morphology operator, the SMDC-connection cost, acting in the 3D space of the thorax volume is defined in order to discriminate lung nodules from other dense (vascular) structures. Applied to clinical data concerning patients with pulmonary carcinoma, the proposed method detects isolated, juxtavascular and peripheral nodules with sizes ranging from 2 to 20 mm diameter. The segmentation accuracy was objectively evaluated on real and simulated nodules. The method showed a sensitivity and a specificity ranging from 85% to 97% and from 90% to 98%, respectively.

Functional calibration procedure for 3D knee joint angle description using inertial sensors.

Measurement of three-dimensional (3D) knee joint angle outside a laboratory is of benefit in clinical examination and therapeutic treatment comparison. Although several motion capture devices exist, there is a need for an ambulatory system that could be used in routine practice. Up-to-date, inertial measurement units (IMUs) have proven to be suitable for unconstrained measurement of knee joint differential orientation. Nevertheless, this differential orientation should be converted into three reliable and clinically interpretable angles. Thus, the aim of this study was to propose a new calibration procedure adapted for the joint coordinate system (JCS), which required only IMUs data. The repeatability of the calibration procedure, as well as the errors in the measurement of 3D knee angle during gait in comparison to a reference system were assessed on eight healthy subjects. The new procedure relying on active and passive movements reported a high repeatability of the mean values (offset<1 degrees) and angular patterns (SD<0.3 degrees and CMC>0.9). In comparison to the reference system, this functional procedure showed high precision (SD<2 degrees and CC>0.75) and moderate accuracy (between 4.0 degrees and 8.1 degrees) for the three knee angle. The combination of the inertial-based system with the functional calibration procedure proposed here resulted in a promising tool for the measurement of 3D knee joint angle. Moreover, this method could be adapted to measure other complex joint, such as ankle or elbow.

A 2D/3D image analysis system to track fluorescently labeled structures in rod-shaped cells: application to measure spindle pole asymmetry during mitosis.

BACKGROUND: The yeast Schizosaccharomyces pombe is frequently used as a model for studying the cell cycle. The cells are rod-shaped and divide by medial fission. The process of cell division, or cytokinesis, is controlled by a network of signaling proteins called the Septation Initiation Network (SIN); SIN proteins associate with the SPBs during nuclear division (mitosis). Some SIN proteins associate with both SPBs early in mitosis, and then display strongly asymmetric signal intensity at the SPBs in late mitosis, just before cytokinesis. This asymmetry is thought to be important for correct regulation of SIN signaling, and coordination of cytokinesis and mitosis. In order to study the dynamics of organelles or large protein complexes such as the spindle pole body (SPB), which have been labeled with a fluorescent protein tag in living cells, a number of the image analysis problems must be solved; the cell outline must be detected automatically, and the position and signal intensity associated with the structures of interest within the cell must be determined. RESULTS: We present a new 2D and 3D image analysis system that permits versatile and robust analysis of motile, fluorescently labeled structures in rod-shaped cells. We have designed an image analysis system that we have implemented as a user-friendly software package allowing the fast and robust image-analysis of large numbers of rod-shaped cells. We have developed new robust algorithms, which we combined with existing methodologies to facilitate fast and accurate analysis. Our software permits the detection and segmentation of rod-shaped cells in either static or dynamic (i.e. time lapse) multi-channel images. It enables tracking of two structures (for example SPBs) in two different image channels. For 2D or 3D static images, the locations of the structures are identified, and then intensity values are extracted together with several quantitative parameters, such as length, width, cell orientation, background fluorescence and the distance between the structures of interest. Furthermore, two kinds of kymographs of the tracked structures can be established, one representing the migration with respect to their relative position, the other representing their individual trajectories inside the cell. This software package, called "RodCellJ", allowed us to analyze a large number of S. pombe cells to understand the rules that govern SIN protein asymmetry. CONCLUSIONS: "RodCell" is freely available to the community as a package of several ImageJ plugins to simultaneously analyze the behavior of a large number of rod-shaped cells in an extensive manner. The integration of different image-processing techniques in a single package, as well as the development of novel algorithms does not only allow to speed up the analysis with respect to the usage of existing tools, but also accounts for higher accuracy. Its utility was demonstrated on both 2D and 3D static and dynamic images to study the septation initiation network of the yeast Schizosaccharomyces pombe. More generally, it can be used in any kind of biological context where fluorescent-protein labeled structures need to be analyzed in rod-shaped cells. AVAILABILITY: RodCellJ is freely available under http://bigwww.epfl.ch/algorithms.html, (after acceptance of the publication).

Comparisons of preoperative three-dimensional planning and surgical reconstruction in primary cementless total hip arthroplasty.

Reconstruction of important parameters such as femoral offset and torsion is inaccurate, when templating is based on plain x-rays. We evaluate intraoperative reproducibility of pre-operative CT-based 3D-templating in a consecutive series of 50 patients undergoing primary cementless THA through an anterior approach. Pre-operative planning was compared to a postoperative CT scan by image fusion. The implant size was correctly predicted in 100% of the stems, 94% of the cups and 88% of the heads (length). The difference between the planned and the postoperative leg length was 0.3 + 2.3 mm. Values for overall offset, femoral anteversion, cup inclination and anteversion were 1.4 mm ± 3.1, 0.6° ± 3.3°, -0.4° ± 5° and 6.9° ± 11.4°, respectively. This planning allows accurate implant size prediction. Stem position and cup inclination are accurately reproducible.

Dual-wavelength digital holographic microscopy with sub-nanometer axial accuracy

We present dual-wavelength Digital Holographic Microscopy (DHM) measurements on a certified 8.9 nm high Chromium thin step sample and demonstrate sub-nanometer axial accuracy. We introduce a modified DHM Reference Calibrated Hologram (RCH) reconstruction algorithm taking into account amplitude contributions. By combining this with a temporal averaging procedure and a specific dual-wavelength DHM arrangement, it is shown that specimen topography can be measured with an accuracy, defined as the axial standard deviation, reduced to at least 0.9 nm. Indeed, it is reported that averaging each of the two wavefronts recorded with real-time dual-wavelength DHM can provide up to 30% spatial noise reduction for the given configuration, thanks to their non-correlated nature. ©2008 COPYRIGHT SPIE

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.

High-resolution 3D whole-heart coronary MRA: a study on the combination of data acquisition in multiple breath-holds and 1D residual respiratory motion compensation.

OBJECT: To study a scan protocol for coronary magnetic resonance angiography based on multiple breath-holds featuring 1D motion compensation and to compare the resulting image quality to a navigator-gated free-breathing acquisition. Image reconstruction was performed using L1 regularized iterative SENSE. MATERIALS AND METHODS: The effects of respiratory motion on the Cartesian sampling scheme were minimized by performing data acquisition in multiple breath-holds. During the scan, repetitive readouts through a k-space center were used to detect and correct the respiratory displacement of the heart by exploiting the self-navigation principle in image reconstruction. In vivo experiments were performed in nine healthy volunteers and the resulting image quality was compared to a navigator-gated reference in terms of vessel length and sharpness. RESULTS: Acquisition in breath-hold is an effective method to reduce the scan time by more than 30 % compared to the navigator-gated reference. Although an equivalent mean image quality with respect to the reference was achieved with the proposed method, the 1D motion compensation did not work equally well in all cases. CONCLUSION: In general, the image quality scaled with the robustness of the motion compensation. Nevertheless, the featured setup provides a positive basis for future extension with more advanced motion compensation methods.

Planar homography: accuracy analysis and applications

Projective homography sits at the heart of many problems in image registration. In addition to many methods for estimating the homography parameters (R.I. Hartley and A. Zisserman, 2000), analytical expressions to assess the accuracy of the transformation parameters have been proposed (A. Criminisi et al., 1999). We show that these expressions provide less accurate bounds than those based on the earlier results of Weng et al. (1989). The discrepancy becomes more critical in applications involving the integration of frame-to-frame homographies and their uncertainties, as in the reconstruction of terrain mosaics and the camera trajectory from flyover imagery. We demonstrate these issues through selected examples

3D virtual rendering before laparoscopic partial splenectomy in children.

INTRODUCTION: Partial splenectomy in children is a good surgical option for hematological diseases and focal splenic tumors because it allows the preservation of the spleen's immunological function. Furthermore, it can be performed by laparoscopy in children as it is a safe procedure, offering the benefits of a minimally invasive approach. MATERIALS AND METHODS: The software VR-render LE version 0.81 is a system that enables the visualization of bidimentional 3D images with magnification of anatomical details. We have applied this system to five cases of non-parasitic splenic cysts before laparoscopic partial splenectomy. RESULTS: The images obtained with VR rendering software permitted the preoperative reconstruction of the vascularization of the splenic hilum, allowing the surgeon safe vessel control during laparoscopic procedures. All five partial splenectomies were carried out with no complications or major blood loss. CONCLUSIONS: Laparoscopic partial splenectomy should be a first choice procedure because it is feasible, reproducible, and safe for children; furthermore, it preserves enough splenic tissue thereby preventing post-splenectomy infections. Volume rendering provides high anatomical resolution and can be useful in guiding the surgical procedure.

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.

Bi-planar 2D-to-3D registration in Fourier domain for stereoscopic X-ray motion tracking

In this paper we present a new method to track bonemovements in stereoscopic X-ray image series of the kneejoint. The method is based on two different X-ray imagesets: a rotational series of acquisitions of the stillsubject knee that will allow the tomographicreconstruction of the three-dimensional volume (model),and a stereoscopic image series of orthogonal projectionsas the subject performs movements. Tracking the movementsof bones throughout the stereoscopic image series meansto determine, for each frame, the best pose of everymoving element (bone) previously identified in the 3Dreconstructed model. The quality of a pose is reflectedin the similarity between its simulated projections andthe actual radiographs. We use direct Fourierreconstruction to approximate the three-dimensionalvolume of the knee joint. Then, to avoid the expensivecomputation of digitally rendered radiographs (DRR) forpose recovery, we reformulate the tracking problem in theFourier domain. Under the hypothesis of parallel X-raybeams, we use the central-slice-projection theorem toreplace the heavy 2D-to-3D registration of projections inthe signal domain by efficient slice-to-volumeregistration in the Fourier domain. Focusing onrotational movements, the translation-relevant phaseinformation can be discarded and we only consider scalarFourier amplitudes. The core of our motion trackingalgorithm can be implemented as a classical frame-wiseslice-to-volume registration task. Preliminary results onboth synthetic and real images confirm the validity ofour approach.

A post-processing pipeline to reconstruct the developing fetal brain using low-resolution MRI

Introduction. Development of the fetal brain surfacewith concomitant gyrification is one of the majormaturational processes of the human brain. Firstdelineated by postmortem studies or by ultrasound, MRIhas recently become a powerful tool for studying in vivothe structural correlates of brain maturation. However,the quantitative measurement of fetal brain developmentis a major challenge because of the movement of the fetusinside the amniotic cavity, the poor spatial resolution,the partial volume effect and the changing appearance ofthe developing brain. Today extensive efforts are made todeal with the âeurooepost-acquisitionâeuro reconstruction ofhigh-resolution 3D fetal volumes based on severalacquisitions with lower resolution (Rousseau, F., 2006;Jiang, S., 2007). We here propose a framework devoted tothe segmentation of the basal ganglia, the gray-whitetissue segmentation, and in turn the 3D corticalreconstruction of the fetal brain. Method. Prenatal MRimaging was performed with a 1-T system (GE MedicalSystems, Milwaukee) using single shot fast spin echo(ssFSE) sequences in fetuses aged from 29 to 32gestational weeks (slice thickness 5.4mm, in planespatial resolution 1.09mm). For each fetus, 6 axialvolumes shifted by 1 mm were acquired (about 1 min pervolume). First, each volume is manually segmented toextract fetal brain from surrounding fetal and maternaltissues. Inhomogeneity intensity correction and linearintensity normalization are then performed. A highspatial resolution image of isotropic voxel size of 1.09mm is created for each fetus as previously published byothers (Rousseau, F., 2006). B-splines are used for thescattered data interpolation (Lee, 1997). Then, basalganglia segmentation is performed on this superreconstructed volume using active contour framework witha Level Set implementation (Bach Cuadra, M., 2010). Oncebasal ganglia are removed from the image, brain tissuesegmentation is performed (Bach Cuadra, M., 2009). Theresulting white matter image is then binarized andfurther given as an input in the Freesurfer software(http://surfer.nmr.mgh.harvard.edu/) to provide accuratethree-dimensional reconstructions of the fetal brain.Results. High-resolution images of the cerebral fetalbrain, as obtained from the low-resolution acquired MRI,are presented for 4 subjects of age ranging from 29 to 32GA. An example is depicted in Figure 1. Accuracy in theautomated basal ganglia segmentation is compared withmanual segmentation using measurement of Dice similarity(DSI), with values above 0.7 considering to be a verygood agreement. In our sample we observed DSI valuesbetween 0.785 and 0.856. We further show the results ofgray-white matter segmentation overlaid on thehigh-resolution gray-scale images. The results arevisually checked for accuracy using the same principlesas commonly accepted in adult neuroimaging. Preliminary3D cortical reconstructions of the fetal brain are shownin Figure 2. Conclusion. We hereby present a completepipeline for the automated extraction of accuratethree-dimensional cortical surface of the fetal brain.These results are preliminary but promising, with theultimate goal to provide âeurooemovieâeuro of the normal gyraldevelopment. In turn, a precise knowledge of the normalfetal brain development will allow the quantification ofsubtle and early but clinically relevant deviations.Moreover, a precise understanding of the gyraldevelopment process may help to build hypotheses tounderstand the pathogenesis of several neurodevelopmentalconditions in which gyrification have been shown to bealtered (e.g. schizophrenia, autismâeuro¦). References.Rousseau, F. (2006), 'Registration-Based Approach forReconstruction of High-Resolution In Utero Fetal MR Brainimages', IEEE Transactions on Medical Imaging, vol. 13,no. 9, pp. 1072-1081. Jiang, S. (2007), 'MRI of MovingSubjects Using Multislice Snapshot Images With VolumeReconstruction (SVR): Application to Fetal, Neonatal, andAdult Brain Studies', IEEE Transactions on MedicalImaging, vol. 26, no. 7, pp. 967-980. Lee, S. (1997),'Scattered data interpolation with multilevel B-splines',IEEE Transactions on Visualization and Computer Graphics,vol. 3, no. 3, pp. 228-244. Bach Cuadra, M. (2010),'Central and Cortical Gray Mater Segmentation of MagneticResonance Images of the Fetal Brain', ISMRM Conference.Bach Cuadra, M. (2009), 'Brain tissue segmentation offetal MR images', MICCAI.

A history of the renewal of the corneal epithelium : a 3D animation

Background: To compare the different schemes that have been proposed during the last thirteen years to explain the renewal of the corneal epithelium. Material and Methods:We analyzed all the data present in the literature to explain the renewal of the corneal epithelium in mammals. According to the schemes proposed in the literature we developed a 3D animation to facilitate the understanding of the different concepts. Results:Three different schemes have been proposed to explain the renewal of the corneal epithelium in mammals during the last thirteen years. 1950-1981: the corneal epithelium was thought being renewed by mitosis of cells located in the basal layer. At this time scientist were not talking about stem cells. 1981-1986 was the period of the "XYZ hypothesis" or the transdifferentiation paradigm. At this time the conjunctival epithelium renewed the corneal epithelium in a centripetal migration. 1986-2008: the limbal stem cell paradigm, there were no stem cells in the corneal epithelium, all the corneal stem cells were located in the limbus and renewed the central cornea after a migration of 6 to 7 mm of transient amplifying cells toward the centre of the cornea. 2008, epithelial stem cells were found in the central cornea in mammals (Nature, Majo et al. November 2008). Discussion:We thought that the renewal of the corneal epithelium was completely defined. According to the last results we published in Nature, the current paradigm will be revisited. The experiments we made were on animals and the final demonstration on human has still to be done. If we find the same results in human, a new paradigm will be define and will change the way we consider ocular surface therapy and reconstruction.