Echocardiographic assessment of mitral regurgitation: discussion of practical and methodologic aspects of severity quantification to improve diagnostic conclusiveness.

The echocardiographic assessment of mitral valve regurgitation (MR) by characterizing specific morphological features and grading its severity is still challenging. Analysis of MR etiology is necessary to clarify the underlying pathological mechanism of the valvular defect. Severity of mitral regurgitation is often quantified based on semi-quantitative parameters. However, incongruent findings and/or interpretations of regurgitation severity are frequently observed. This proposal seeks to offer practical support to overcome these obstacles by offering a standardized workflow, an easy means to identify non-severe mitral regurgitation, and by focusing on the quantitative approach with calculation of the individual regurgitant fraction. This work also indicates main methodological problems of semi-quantitative parameters when evaluating MR severity and offers appropriateness criteria for their use. It addresses the diagnostic importance of left-ventricular wall thickness, left-ventricular and left atrial volumes in relation to disease progression, and disease-related complaints to improve interpretation of echocardiographic findings. Finally, it highlights the conditions influencing the MR dynamics during echocardiographic examination. These considerations allow a reproducible, verifiable, and transparent in-depth echocardiographic evaluation of MR patients ensuring consistent haemodynamic plausibility of echocardiographic results.

A refined reaction-diffusion model of tau-microtubule dynamics and its application in FDAP analysis.

Fluorescence decay after photoactivation (FDAP) and fluorescence recovery after photobleaching (FRAP) are well established approaches for studying the interaction of the microtubule (MT)-associated protein tau with MTs in neuronal cells. Previous interpretations of FDAP/FRAP data have revealed dwell times of tau on MTs in the range of several seconds. However, this is difficult to reconcile with a dwell time recently measured by single-molecule analysis in neuronal processes that was shorter by two orders of magnitude. Questioning the validity of previously used phenomenological interpretations of FDAP/FRAP data, we have generalized the standard two-state reaction-diffusion equations by 1), accounting for the parallel and discrete arrangement of MTs in cell processes (i.e., homogeneous versus heterogeneous distribution of tau-binding sites); and 2), explicitly considering both active (diffusion upon MTs) and passive (piggybacking upon MTs at rates of slow axonal transport) motion of bound tau. For some idealized cases, analytical solutions were derived. By comparing them with the full numerical solution and Monte Carlo simulations, the respective validity domains were mapped. Interpretation of our FDAP data (from processes of neuronally differentiated PC12 cells) in light of the heterogeneous formalism yielded independent estimates for the association (∼2 ms) and dwell (∼100 ms) times of tau to/on a single MT rather than in an MT array. The dwell time was shorter by orders of magnitude than that in a previous report where a homogeneous topology of MTs was assumed. We found that the diffusion of bound tau was negligible in vivo, in contrast to an earlier report that tau diffuses along the MT lattice in vitro. Methodologically, our results demonstrate that the heterogeneity of binding sites cannot be ignored when dealing with reaction-diffusion of cytoskeleton-associated proteins. Physiologically, the results reveal the behavior of tau in cellular processes, which is noticeably different from that in vitro.

Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons.

The microtubule-associated phosphoprotein tau regulates microtubule dynamics and is involved in neurodegenerative diseases collectively called tauopathies. It is generally believed that the vast majority of tau molecules decorate axonal microtubules, thereby stabilizing them. However, it is an open question how tau can regulate microtubule dynamics without impeding microtubule-dependent transport and how tau is also available for interactions other than those with microtubules. Here we address this apparent paradox by fast single-molecule tracking of tau in living neurons and Monte Carlo simulations of tau dynamics. We find that tau dwells on a single microtubule for an unexpectedly short time of ∼40 ms before it hops to the next. This dwell time is 100-fold shorter than previously reported by ensemble measurements. Furthermore, we observed by quantitative imaging using fluorescence decay after photoactivation recordings of photoactivatable GFP-tagged tubulin that, despite this rapid dynamics, tau is capable of regulating the tubulin-microtubule balance. This indicates that tau's dwell time on microtubules is sufficiently long to influence the lifetime of a tubulin subunit in a GTP cap. Our data imply a novel kiss-and-hop mechanism by which tau promotes neuronal microtubule assembly. The rapid kiss-and-hop interaction explains why tau, although binding to microtubules, does not interfere with axonal transport.

Multi-detector computed tomography is equivalent to trans-oesophageal echocardiography for the assessment of the aortic annulus before transcatheter aortic valve implantation.

OBJECTIVES: In transcatheter aortic valve implantation (TAVI), assessment of the aortic annulus is mandatory. We sought to investigate the correlation between trans-oesophageal echocardiography (TEE) and multi-detector computed tomography (MDCT) for annulus diameter assessment before TAVI. METHODS: A total of 122 patients (67 male, mean age 84 ± 6 years) underwent MDCT and TEE for TAVI planning. In TEE annulus diameters were obtained in a long-axis view at diastole. MDCT data were evaluated using MPR images, and corresponding projections were adjusted for MDCT and TEE. Patients were classified by the predominant localisation of aortic valve calcifications, and annulus diameters between TEE and MDCT were correlated. Additionally, the eccentricity of the aortic annulus was calculated. RESULTS: Mean eccentricity of the aortic annulus determined by MDCT was 0.34 ± 0.17, with no difference according to valve calcification. Regarding the aortic annulus diameter, the mean values measured were 24.3 ± 2.1 mm in MDCT and 24.0 ± 2.5 mm in TEE (P < 0.0001 for agreement). CONCLUSIONS: Independent of the pattern of aortic valve calcification, close correlation is found between CT and TEE measurements of the aortic annulus diameter. In addition, CT demonstrates the non-circular shape of the aortic annulus. KEY POINTS: Accurate assessment of aortic annulus before transcatheter aortic valve implantation is crucial. Trans-oesophageal echocardiography has been the preferred method for aortic annulus assessment. We demonstrated a strong correlation between TEE and CT for annulus dimensions. CT reliably demonstrates the non-circular shape of the aortic annulus. CT could therefore be generally used for aortic annulus assessment before TAVI.