Automated left ventricular diastolic function evaluation from phase-contrast cardiovascular magnetic resonance and comparison with Doppler echocardiography

International audienceBACKGROUND: Early detection of diastolic dysfunction is crucial for patients with incipient heart failure. Although this evaluation could be performed from phase-contrast (PC) cardiovascular magnetic resonance (CMR) data, its usefulness in clinical routine is not yet established, mainly because the interpretation of such data remains mostly based on manual post-processing. Accordingly, our goal was to develop a robust process to automatically estimate velocity and flow rate-related diastolic parameters from PC-CMR data and to test the consistency of these parameters against echocardiography as well as their ability to characterize left ventricular (LV) diastolic dysfunction. RESULTS: We studied 35 controls and 18 patients with severe aortic valve stenosis and preserved LV ejection fraction who had PC-CMR and Doppler echocardiography exams on the same day. PC-CMR mitral flow and myocardial velocity data were analyzed using custom software for semi-automated extraction of diastolic parameters. Inter-operator reproducibility of flow pattern segmentation and functional parameters was assessed on a sub-group of 30 subjects. The mean percentage of overlap between the transmitral flow segmentations performed by two independent operators was 99.7 ± 1.6%, resulting in a small variability ( 0.71) and receiver operating characteristic (ROC) analysis revealed their ability to separate patients from controls, with sensitivity > 0.80, specificity > 0.80 and accuracy > 0.85. Slight superiority in terms of correlation with echocardiography (r = 0.81) and accuracy to detect LV abnormalities (sensitivity > 0.83, specificity > 0.91 and accuracy > 0.89) was found for the PC-CMR flow-rate related parameters. CONCLUSIONS: A fast and reproducible technique for flow and myocardial PC-CMR data analysis was successfully used on controls and patients to extract consistent velocity-related diastolic parameters, as well as flow rate-related parameters. This technique provides a valuable addition to established CMR tools in the evaluation and the management of patients with diastolic dysfunction

CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes.

CD5 is constitutively expressed on T cells and a subset of mature normal and leukemic B cells in patients with chronic lymphocytic leukemia (CLL). Important functional properties are associated with CD5 expression in B cells, including signal transducer and activator of transcription 3 activation, IL-10 production and the promotion of B-lymphocyte survival and transformation. However, the pathway(s) by which CD5 influences the biology of B cells and its dependence on B-cell receptor (BCR) co-signaling remain unknown. In this study, we show that CD5 expression activates a number of important signaling pathways, including Erk1/2, leading to IL-10 production through a novel pathway independent of BCR engagement. This pathway is dependent on extracellular calcium (Ca2+) entry facilitated by upregulation of the transient receptor potential channel 1 (TRPC1) protein. We also show that Erk1/2 activation in a subgroup of CLL patients is associated with TRPC1 overexpression. In this subgroup of CLL patients, small inhibitory RNA (siRNA) for CD5 reduces TRPC1 expression. Furthermore, siRNAs for CD5 or for TRPC1 inhibit IL-10 production. These findings provide new insights into the role of CD5 in B-cell biology in health and disease and could pave the way for new treatment strategies for patients with B-CLL

Electron impact single ionization and dissociative excitation of H3O+, HD2O+ and D3O+

First absolute cross sections for electron impact single ionization of H3O+, HD2O+ and D3O+ and for dissociative excitation (DE) producing H+ and D+ are reported. The animated crossed electron-ion beam method has been employed in the energy range from threshold to 2500 eV. The maxima of these cross sections are found to be unusually small (<1 x 10(-17) cm(2)). The ionization threshold energies are determined to be 24.7 +/- 0.5, 24.4 +/- 0.5 and 24.0 +/- 0.5 eV for H3O+, HD2O+ and D3O+, respectively. The observed DE threshold energies lie in the range 10-12.5 eV and the maximum kinetic energies released are between 3 and 4 eV. Significant differences are observed between the results obtained for the three isotopomers

Electron impact ionization and dissociation of CO2+ to C+ and O+

Absolute cross sections for electron impact ionization and dissociation of CO2+ to form C+ and O+ fragments are measured in the energy range from threshold to 2500 eV. The animated crossed-beams method has been employed. The ionization cross section shows a maximum of 4.79 x 10(-17) cm(2) at 130 eV and the corresponding threshold is found in good agreement with previous measurements. Both dissociation cross sections are shown to exhibit wide plateaux which are of the same order of magnitude. In addition, these cross sections almost coincide above 100 eV. The threshold energy and kinetic energy released are determined for both the production of C+ and O+. They are found in good agreement with the previously published data obtained in electron impact ionization experiments of neutral CO2

Electron impact dissociation and ionization of N-2(+)

Absolute cross sections for electron impact ionization, dissociative excitation (DE) and dissociative ionization of N-2(+) ions are measured in the energy range from threshold to 2500 eV. The animated crossed electron-ion beam method has been employed. The individual contributions of ionization products (N-2(2+)) and dissociation fragments (N+), which have both identical mass-to-charge ratio and average velocity, are deduced from the analysis of product velocity distributions. Particular attention was paid to determining the transmission efficiency for dissociation fragments, since their collection was incomplete during the measurements. Threshold energies and kinetic energy released to dissociation fragments are measured. The role of states contributing to different reactions is discussed. For DE, the present results are found to be much smaller than the results of Peterson et al (1998). For ionization (single and dissociative), a satisfactory agreement with their result is obtained as well as with the prediction of Kim et al (2000) obtained in the binary-encounter Bethe approximation

On the behaviour of the (e, 3e) total cross section for helium at high and intermediate energies

Applying the animated beam method the total cross sections (TCS) for double ionization (DI) of helium by electrons are measured in the collision energy region from threshold to 3 keV. The TCS for the same process are calculated at intermediate and high incident energies in the first Born approximation (FBA). The radial and angular correlations between the bound electrons and repulsion between the ejected electrons are accounted. In order to go beyond the FBA the scattered electron is considered as a particle being in the Coulomb field of the nucleus, the charge of which is screened by the ejected electrons. On the basis of the obtained results some conclusions concerning the behaviour of the TCS in the intermediate and high-energy regions are drawn

Discovery of novel and selective tertiary alcohol containing inhibitors of the norepinephrine transporter

A novel series of tertiary alcohol containing 2-substituted benzyl morpholines have been discovered as potent and selective inhibitors of the norepinephrine transporter. Efficient synthetic routes were developed featuring a highly diastereoselective nucleophilic addition of benzyl Grignard reagents to enantiopure (4-benzylmorpholin-2-yl)phenylmethanone (11) as the key synthetic step. In vitro binding affinity for the norepinephrine, dopamine and serotonin transporters and in vivo examination of a select compound (16) in a pharmacodynamic animal model for norepinephrine reuptake inhibition are presented. (C) 2005 Elsevier Ltd. All rights reserved