0059 : Non invasive ultrasonic chordal cutting

ObjectiveChordal cutting targeting leaflet tethering has been described to improve the efficiency of annuloplasty during ischemic mitral regurgitation surgery. Histotripsy is an ultrasound based technique for tissue fragmentation through the cavitation generated by a very intense ultrasonic pulse. In this study we investigate the feasibility of using histotripsy for chordal cutting to avoid cardiopulmonary bypass and invasive surgery in infarcted heart.MethodsExperiments were performed in vitro in explanted sheep heart (N=10) and in vivo in sheep beating heart (N=5, 40+/-4kg). In vitro, the mitral valve basal chordae was removed, fixed on a holder in a water tank. The ultrasound pulses were emitted from the therapeutic device (1- MHz focused transducer, pulses of 8μs duration, peak negative pressure of 17 MPa, repetition frequency of 100Hz) placed at a distance of 64mm. In vivo, we performed sternotomy and the device was applied on the thorax cavity which was filled out with water. We analysed MV coaptation and chordae by real time 3D echocardiography. The animals were sacrificed at the end of the procedure, for postmortem anatomical exploration of the heart.ResultsIn vitro, all the basal chordae were completely cut. The mean procedure time was 5.5 (+/-1.7) minutes. The diameter of the chordae was the main criteria affecting the duration of procedure. In the sheep, central basal chordae of anterior leaflet were completely cut. The mean procedure time was 22 (+/-9) minutes. By echography, the sectioned chordae was visible and no mitral valve prolapse was found. All the postmortem anatomical exploration of hearts confirmed the section of the basal chordea. No additional lesions were objectified.ConclusionsNoninvasive ultrasound histotripsy succeed to cut mitral valve basal chordae in vitro and in vivo in beating heart. If positive, this will open the door of completely noninvasive technique for MV repair especially in case of ischemic or functional MR

Imaging the dynamics of cardiac fiber orientation in vivo using 3D Ultrasound Backscatter Tensor Imaging

The assessment of myocardial fiber disarray is of major interest for the study of the progression of myocardial disease. However, time-resolved imaging of the myocardial structure remains unavailable in clinical practice. In this study, we introduce 3D Backscatter Tensor Imaging (3D-BTI), an entirely novel ultrasound-based imaging technique that can map the myocardial fibers orientation and its dynamics with a temporal resolution of 10 ms during a single cardiac cycle, non-invasively and in vivo in entire volumes. 3D-BTI is based on ultrafast volumetric ultrasound acquisitions, which are used to quantify the spatial coherence of backscattered echoes at each point of the volume. The capability of 3D-BTI to map the fibers orientation was evaluated in vitro in 5 myocardial samples. The helicoidal transmural variation of fiber angles was in good agreement with the one obtained by histological analysis. 3D-BTI was then performed to map the fiber orientation dynamics in vivo in the beating heart of an open-chest sheep at a volume rate of 90 volumes/s. Finally, the clinical feasibility of 3D-BTI was shown on a healthy volunteer. These initial results indicate that 3D-BTI could become a fully non-invasive technique to assess myocardial disarray at the bedside of patients

Algorithme de contour actif appliqué à la poursuite d'avalanche

Le traitement d'image est un outil de plus en plus utilisé dans l'étude des avalanches de neige, ceci dans le but de les prévenir. On présente ici un algorithme de contour actif spécifique à notre application : l'analyse du front des avalanches. Le but de cette étude consiste en l'extraction de paramètres dynamiques de l'avalanche à partir d'un simple film vidéo. La principale difficulté réside dans le manque évident de contraste de nos images, puisque nous avons à poursuivre un objet blanc sur un fond blanc. L'algorithme présenté repose sur le principe des contours actifs, où on recherche à minimiser une forme énergétique modélisant le contour de l'avalanche. Le résultat obtenu est une séquence de contour d'avalanche

Biotransformation of anthracene and fluoranthene by Absidia fusca Linnemann

A strain of Absidia fusca was isolated from a pesticide-contaminated soil (Annaba, Algeria). The biotransformation capability of this strain towards two polycyclic aromatic hydrocarbons (PAHs): anthracene and fluoranthene was compared to that exhibited by another strain of A. fusca isolated from a non-contaminated milieu and considered as a control. The results obtained were statistically analyzed and showed that the strain isolated from the contaminated soil was more efficient than the control to remove anthracene from the medium, during all the kinetics (90% removed versus 45% after 24 hrs). Concerning fluoranthene, the amount removed by both strains was very high during the first 24 hrs however the control strain was slightly more efficient (94% versus 89%) while the results were similar for the two strains during the rest of the kinetics. This study reveals for the first time the potential interest of the species A. fusca for the bioremediation of PAHs

Imaging the dynamics of cardiac fiber orientation in vivo using 3D Ultrasound Backscatter Tensor Imaging

ABSTRACT: The assessment of myocardial fiber disarray is of major interest for the study of the progression of myocardial disease. However, time-resolved imaging of the myocardial structure remains unavailable in clinical practice. In this study, we introduce 3D Backscatter Tensor Imaging (3D-BTI), an entirely novel ultrasound-based imaging technique that can map the myocardial fibers orientation and its dynamics with a temporal resolution of 10 ms during a single cardiac cycle, non-invasively and in vivo in entire volumes. 3D-BTI is based on ultrafast volumetric ultrasound acquisitions, which are used to quantify the spatial coherence of backscattered echoes at each point of the volume. The capability of 3D-BTI to map the fibers orientation was evaluated in vitro in 5 myocardial samples. The helicoidal transmural variation of fiber angles was in good agreement with the one obtained by histological analysis. 3D-BTI was then performed to map the fiber orientation dynamics in vivo in the beating heart of an open-chest sheep at a volume rate of 90 volumes/s. Finally, the clinical feasibility of 3D-BTI was shown on a healthy volunteer. These initial results indicate that 3D-BTI could become a fully non-invasive technique to assess myocardial disarray at the bedside of patients

Tacrolimus Population Pharmacokinetic-Pharmacogenetic Analysis and Bayesian Estimation in Renal Transplant Recipients

Objectives: The aims of this study were (i) to investigate the population pharmacokinetics of tacrolimus in renal transplant recipients, including the influence of biological and pharmacogenetic covariates; and (ii) to develop a Bayesian estimator able to reliably estimate the individual pharmacokinetic parameters and inter-dose area under the blood concentration-time curve (AUC) from 0 to 12 hours (AUC12) in renal transplant patients. Methods: Full pharmacokinetic profiles were obtained from 32 renal transplant patients at weeks 1 and 2, and at months 1, 3 and 6 post-transplantation. The population pharmacokinetic analysis was performed using the nonlinear mixed-effect modelling software NONMEM® version VI. Patients’ genotypes were characterized by allelic discrimination for PXR −25385C>T genes. Results: Tacrolimus pharmacokinetics were well described by a two-compartment model combined with an Erlang distribution to describe the absorption phase, with low additive and proportional residual errors of 1.6 ng/mL and 9%, respectively. Both the haematocrit and PXR −25385C>T single nucleotide polymorphism (SNP) were identified as significant covariates for apparent oral clearance (CL/F) of tacrolimus, which allowed improvement of prediction accuracy. Specifically, CL/F decreased gradually with the number of mutated alleles for the PXR −25385C>T SNP and was inversely proportional to the haematocrit value. However, clinical criteria of relevance, mainly the decrease in interindividual variability and residual error, led us to retain only the haematocrit in the final model. Maximum a posteriori Bayesian forecasting allowed accurate prediction of the tacrolimus AUC12 using only three sampling times (at 0 hour [predose] and at 1 and 3 hours postdose) in addition to the haematocrit value, with a nonsignificant mean AUC bias of 2% and good precision (relative mean square error = 11%). Conclusion: Population pharmacokinetic analysis of tacrolimus in renal transplant recipients showed a significant influence of the haematocrit on its CL/F and led to the development of a Bayesian estimator compatible with clinical practice and able to accurately predict tacrolimus individual pharmacokinetic parameters and the AUC12

Opening-closing dynamics of the mitochondrial transcription pre-initiation complex

Promoter recognition and local melting of DNA are key steps of transcription initiation catalyzed by RNA polymerase and initiation factors. From single molecule fluorescence resonance energy transfer studies of the yeast (Saccharomyces cerevisiae) mitochondrial RNA polymerase Rpo41 and its transcription factor Mtf1, we show that the pre-initiation complex is highly dynamic and undergoes repetitive opening-closing transitions that are modulated by Mtf1 and ATP. We found that Rpo41 alone has the intrinsic ability to bend the promoter but only very briefly. Mtf1 enhances bending/opening transition and suppresses closing transition, indicating its dual roles of nucleating promoter opening and stabilizing the open state. The cognate initiating ATP prolongs the lifetime of the open state, plausibly explaining the 'ATP sensing mechanism' suggested for the system. We discovered short-lived opening trials upon initial binding of Rpo41-Mtf1 before the establishment of the opening/closing equilibrium, which may aid in promoter selection before the formation of stable pre-initiation complex. The dynamics of open complex formation provides unique insights into the interplay between RNA polymerase and transcription factors in regulating initiation.open4