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.

Increased brain perfusion contrast with T2 -prepared intravoxel incoherent motion (T2prep IVIM) MRI.

The feasibility to measure brain perfusion using intravoxel incoherent motion (IVIM) MRI has been reported recently with currently clinically available technology. The method is intrinsically local and quantitative, but is contaminated by partial volume effects with cerebrospinal fluid (CSF). Signal from CSF can be suppressed by a 180° inversion recovery (180°-IR) magnetization preparation, but this also leads to strong suppression of blood and brain tissue signal. Here, we take advantage of the different T2 relaxations of blood and brain relative to CSF, and implement a T2 -prepared IVIM (T2prep IVIM) inversion recovery acquisition, which permits a recovery of between 43% and 57% of arterial and venous blood magnetization at excitation time compared with the theoretical recovery of between 27% and 30% with a standard 180°-IR. We acquired standard IVIM (IVIM), T2prep IVIM and dynamic susceptibility contrast (DSC) images at 3 T using a 32-multichannel receiver head coil in eight patients with known large high-grade brain tumors. We compared the contrast and contrast-to-noise ratio obtained in the corresponding cerebral blood volume images quantitatively, as well as subjectively by two neuroradiologists. Our findings suggest that quantitative cerebral blood volume contrast and contrast-to-noise ratio, as well as subjective lesion detection, contrast quality and diagnostic confidence, are increased with T2prep IVIM relative to IVIM and DSC.

Zonation for 3D aquifer characterization based on joint inversions of multimethod crosshole geophysical data

Predictive groundwater modeling requires accurate information about aquifer characteristics. Geophysical imaging is a powerful tool for delineating aquifer properties at an appropriate scale and resolution, but it suffers from problems of ambiguity. One way to overcome such limitations is to adopt a simultaneous multitechnique inversion strategy. We have developed a methodology for aquifer characterization based on structural joint inversion of multiple geophysical data sets followed by clustering to form zones and subsequent inversion for zonal parameters. Joint inversions based on cross-gradient structural constraints require less restrictive assumptions than, say, applying predefined petro-physical relationships and generally yield superior results. This approach has, for the first time, been applied to three geophysical data types in three dimensions. A classification scheme using maximum likelihood estimation is used to determine the parameters of a Gaussian mixture model that defines zonal geometries from joint-inversion tomograms. The resulting zones are used to estimate representative geophysical parameters of each zone, which are then used for field-scale petrophysical analysis. A synthetic study demonstrated how joint inversion of seismic and radar traveltimes and electrical resistance tomography (ERT) data greatly reduces misclassification of zones (down from 21.3% to 3.7%) and improves the accuracy of retrieved zonal parameters (from 1.8% to 0.3%) compared to individual inversions. We applied our scheme to a data set collected in northeastern Switzerland to delineate lithologic subunits within a gravel aquifer. The inversion models resolve three principal subhorizontal units along with some important 3D heterogeneity. Petro-physical analysis of the zonal parameters indicated approximately 30% variation in porosity within the gravel aquifer and an increasing fraction of finer sediments with depth.

Flow targeted 3D steady-state free-precession coronary MR angiography: comparison of three different imaging approaches.

PURPOSE: To compare 3 different flow targeted magnetization preparation strategies for coronary MR angiography (cMRA), which allow selective visualization of the vessel lumen. MATERIAL AND METHODS: The right coronary artery of 10 healthy subjects was investigated on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Healthcare, Best, NL). A navigator-gated and ECG-triggered 3D radial steady-state free-precession (SSFP) cMRA sequence with 3 different magnetization preparation schemes was performed referred to as projection SSFP (selective labeling of the aorta, subtraction of 2 data sets), LoReIn SSFP (double-inversion preparation, selective labeling of the aorta, 1 data set), and inflow SSFP (inversion preparation, selective labeling of the coronary artery, 1 data set). Signal-to-noise ratio (SNR) of the coronary artery and aorta, contrast-to-noise ratio (CNR) between the coronary artery and epicardial fat, vessel length and vessel sharpness were analyzed. RESULTS: All cMRA sequences were successfully obtained in all subjects. Both projection SSFP and LoReIn SSFP allowed for selective visualization of the coronary arteries with excellent background suppression. Scan time was doubled in projection SSFP because of the need for subtraction of 2 data sets. In inflow SSFP, background suppression was limited to the tissue included in the inversion volume. Projection SSFP (SNR(coro): 25.6 +/- 12.1; SNR(ao): 26.1 +/- 16.8; CNR(coro-fat): 22.0 +/- 11.7) and inflow SSFP (SNR(coro): 27.9 +/- 5.4; SNR(ao): 37.4 +/- 9.2; CNR(coro-fat): 24.9 +/- 4.8) yielded significantly increased SNR and CNR compared with LoReIn SSFP (SNR(coro): 12.3 +/- 5.4; SNR(ao): 11.8 +/- 5.8; CNR(coro-fat): 9.8 +/- 5.5; P < 0.05 for both). Longest visible vessel length was found with projection SSFP (79.5 mm +/- 18.9; P < 0.05 vs. LoReIn) whereas vessel sharpness was best in inflow SSFP (68.2% +/- 4.5%; P < 0.05 vs. LoReIn). Consistently good image quality was achieved using inflow SSFP likely because of the simple planning procedure and short scanning time. CONCLUSION: Three flow targeted cMRA approaches are presented, which provide selective visualization of the coronary vessel lumen and in addition blood flow information without the need of contrast agent administration. Inflow SSFP yielded highest SNR, CNR and vessel sharpness and may prove useful as a fast and efficient approach for assessing proximal and mid vessel coronary blood flow, whereas requiring less planning skills than projection SSFP or LoReIn SSFP.

SIMSAFADIM-CLASTIC: A new approach to mathematical 3D forward simulation modelling for terrigenous and carbonate marine sedimentation

Most sedimentary modelling programs developed in recent years focus on either terrigenous or carbonate marine sedimentation. Nevertheless, only a few programs have attempted to consider mixed terrigenous-carbonate sedimentation, and most of these are two-dimensional, which is a major restriction since geological processes take place in 3D. This paper presents the basic concepts of a new 3D mathematical forward simulation model for clastic sediments, which was developed from SIMSAFADIM, a previous 3D carbonate sedimentation model. The new extended model, SIMSAFADIM-CLASTIC, simulates processes of autochthonous marine carbonate production and accumulation, together with clastic transport and sedimentation in three dimensions of both carbonate and terrigenous sediments. Other models and modelling strategies may also provide realistic and efficient tools for prediction of stratigraphic architecture and facies distribution of sedimentary deposits. However, SIMSAFADIM-CLASTIC becomes an innovative model that attempts to simulate different sediment types using a process-based approach, therefore being a useful tool for 3D prediction of stratigraphic architecture and facies distribution in sedimentary basins. This model is applied to the neogene Vallès-Penedès half-graben (western Mediterranean, NE Spain) to show the capacity of the program when applied to a realistic geologic situation involving interactions between terrigenous clastics and carbonate sediments.

Stochastic delay equations with non-negativity constraints driven by fractional Brownian motion

In this note we prove an existence and uniqueness result for the solution of multidimensional stochastic delay differential equations with normal reflection. The equations are driven by a fractional Brownian motion with Hurst parameter H > 1/2. The stochastic integral with respect to the fractional Brownian motion is a pathwise Riemann¿Stieltjes integral.

Stochastic delay differential equations driven by fractional Brownian motion with Hurst parameter H 1/2

We consider the Cauchy problem for a stochastic delay differential equation driven by a fractional Brownian motion with Hurst parameter H>¿. We prove an existence and uniqueness result for this problem, when the coefficients are sufficiently regular. Furthermore, if the diffusion coefficient is bounded away from zero and the coefficients are smooth functions with bounded derivatives of all orders, we prove that the law of the solution admits a smooth density with respect to Lebesgue measure on R.

Modelización Gravimétrica 3D del diapiro de Cardona, Cuenca del Ebro (NE de España)

En este trabajo se presentan los resultados derivados de la interpretacón de 320 estaciones gravimétricas realizadas sobre el diapiro de Cardona con el objetivo de obtener información sobre su geometría tridimensional. Para obtener una distribución tridimensional de la masa salina que explique las anomalías observadas se ha aplicado un método iterativo de ajustes sucesivos basado en un algoritmo de inversión automática. Esta metodología ha mostrado ser muy rápida, fácil de usar y con suficiente poder de resolución para perfilar no sólo la geometría del cuerpo salino, sino también la de estructuras similares. El diapiro salino de Cardona presenta un mínimo gravimétrico relacionado con el anticlinal de Pins-Cardona que se prolonga hacia el SW. El análisis cualitativo de la anomalía residual permite apreciar que el diapiro muestra una cierta vergencia hacia sur con un flanco sureste subvertical y un flanco noroeste con pendientes más suaves.

Free-breathing 3D coronary MRA: the impact of "isotropic" image resolution.

During conventional x-ray coronary angiography, multiple projections of the coronary arteries are acquired to define coronary anatomy precisely. Due to time constraints, coronary magnetic resonance angiography (MRA) usually provides only one or two views of the major coronary vessels. A coronary MRA approach that allowed for reconstruction of arbitrary isotropic orientations might therefore be desirable. The purpose of the study was to develop a three-dimensional (3D) coronary MRA technique with isotropic image resolution in a relatively short scanning time that allows for reconstruction of arbitrary views of the coronary arteries without constraints given by anisotropic voxel size. Eight healthy adult subjects were examined using a real-time navigator-gated and corrected free-breathing interleaved echoplanar (TFE-EPI) 3D-MRA sequence. Two 3D datasets were acquired for the left and right coronary systems in each subject, one with anisotropic (1.0 x 1.5 x 3.0 mm, 10 slices) and one with "near" isotropic (1.0 x 1.5 x 1.0 mm, 30 slices) image resolution. All other imaging parameters were maintained. In all cases, the entire left main (LM) and extensive portions of the left anterior descending (LAD) and the right coronary artery (RCA) were visualized. Objective assessment of coronary vessel sharpness was similar (41% +/- 5% vs. 42% +/- 5%; P = NS) between in-plane and through-plane views with "isotropic" voxel size but differed (32% +/- 7% vs. 23% +/- 4%; P < 0.001) with nonisotropic voxel size. In reconstructed views oriented in the through-plane direction, the vessel border was 86% more defined (P < 0.01) for isotropic compared with anisotropic images. A smaller (30%; P < 0.001) improvement was seen for in-plane reconstructions. Vessel diameter measurements were view independent (2.81 +/- 0.45 mm vs. 2.66 +/- 0.52 mm; P = NS) for isotropic, but differed (2.71 +/- 0.51 mm vs. 3.30 +/- 0.38 mm; P < 0.001) between anisotropic views. Average scanning time was 2:31 +/- 0:57 minutes for anisotropic and 7:11 +/- 3:02 minutes for isotropic image resolution (P < 0.001). We present a new approach for "near" isotropic 3D coronary artery imaging, which allows for reconstruction of arbitrary views of the coronary arteries. The good delineation of the coronary arteries in all views suggests that isotropic 3D coronary MRA might be a preferred technique for the assessment of coronary disease, although at the expense of prolonged scan times. Comparative studies with conventional x-ray angiography are needed to investigate the clinical utility of the isotropic strategy.

Measuring brain perfusion with intravoxel incoherent motion (IVIM): Initial clinical experience.

PURPOSE: To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the brain with currently available imaging systems. MATERIALS AND METHODS: We acquired high in-plane resolution (1.2 × 1.2 mm(2) ) diffusion-weighted images with 16 different values of b ranging from 0 to 900 s/mm(2) , in three orthogonal directions, on 3T systems with a 32-multichannel receiver head coil. IVIM perfusion maps were extracted by fitting a double exponential model of signal amplitude decay. Regions of interest were drawn in pathological and control regions, where IVIM perfusion parameters were compared to the corresponding dynamic susceptibility contrast (DSC) parameters. RESULTS: Hyperperfusion was found in the nonnecrotic or cystic part of two histologically proven glioblastoma multiforme and in two histologically proven glioma WHO grade III, as well as in a brain metastasis of lung adenocarcinoma, in a large meningioma, and in a case of ictal hyperperfusion. A monoexponential decay was found in a territory of acute ischemia, as well as in the necrotic part of a glioblastoma. The IVIM perfusion fraction f correlated well with DSC CBV. CONCLUSION: Our initial report suggests that high-resolution brain perfusion imaging is feasible with IVIM in the current clinical setting. J. Magn. Reson. Imaging 2014;39:624-632. © 2013 Wiley Periodicals, Inc.

From protein sequences to 3D-structures and beyond: the example of the UniProt knowledgebase.

With the dramatic increase in the volume of experimental results in every domain of life sciences, assembling pertinent data and combining information from different fields has become a challenge. Information is dispersed over numerous specialized databases and is presented in many different formats. Rapid access to experiment-based information about well-characterized proteins helps predict the function of uncharacterized proteins identified by large-scale sequencing. In this context, universal knowledgebases play essential roles in providing access to data from complementary types of experiments and serving as hubs with cross-references to many specialized databases. This review outlines how the value of experimental data is optimized by combining high-quality protein sequences with complementary experimental results, including information derived from protein 3D-structures, using as an example the UniProt knowledgebase (UniProtKB) and the tools and links provided on its website ( http://www.uniprot.org/ ). It also evokes precautions that are necessary for successful predictions and extrapolations.

Model-based Segmentation and Image Fusion of 3D Computed Tomography and 3D Ultrasound of the Eye for Radiotherapy Planning

For radiotherapy treatment planning of retinoblastoma inchildhood, Computed Tomography (CT) represents thestandard method for tumor volume delineation, despitesome inherent limitations. CT scan is very useful inproviding information on physical density for dosecalculation and morphological volumetric information butpresents a low sensitivity in assessing the tumorviability. On the other hand, 3D ultrasound (US) allows ahigh accurate definition of the tumor volume thanks toits high spatial resolution but it is not currentlyintegrated in the treatment planning but used only fordiagnosis and follow-up. Our ultimate goal is anautomatic segmentation of gross tumor volume (GTV) in the3D US, the segmentation of the organs at risk (OAR) inthe CT and the registration of both. In this paper, wepresent some preliminary results in this direction. Wepresent 3D active contour-based segmentation of the eyeball and the lens in CT images; the presented approachincorporates the prior knowledge of the anatomy by usinga 3D geometrical eye model. The automated segmentationresults are validated by comparing with manualsegmentations. Then, for the fusion of 3D CT and USimages, we present two approaches: (i) landmark-basedtransformation, and (ii) object-based transformation thatmakes use of eye ball contour information on CT and USimages.

Direct three-dimensional myocardial strain tensor quantification and tracking using zHARP.

Images of myocardial strain can be used to diagnose heart disease, plan and monitor treatment, and to learn about cardiac structure and function. Three-dimensional (3D) strain is typically quantified using many magnetic resonance (MR) images obtained in two or three orthogonal planes. Problems with this approach include long scan times, image misregistration, and through-plane motion. This article presents a novel method for calculating cardiac 3D strain using a stack of two or more images acquired in only one orientation. The zHARP pulse sequence encodes in-plane motion using MR tagging and out-of-plane motion using phase encoding, and has been previously shown to be capable of computing 3D displacement within a single image plane. Here, data from two adjacent image planes are combined to yield a 3D strain tensor at each pixel; stacks of zHARP images can be used to derive stacked arrays of 3D strain tensors without imaging multiple orientations and without numerical interpolation. The performance and accuracy of the method is demonstrated in vitro on a phantom and in vivo in four healthy adult human subjects.