Renzo Antolini

A method for quantifying atrial fibrillation organization based on wave-morphology similarity

A new method for quantifying the organization of single bipolar electrograms recorded in the human atria during atrial fibrillation (AF) is presented. The algorithm relies on the comparison between pairs of local activation waves (LAWs) to estimate their morphological similarity, and returns a regularity index (/spl rho/) which measures the extent of repetitiveness over time of the detected activations. The database consisted of endocardial data from a multipolar basket catheter during AF and intraatrial recordings during atrial flutter. The index showed maximum regularity (/spl rho/=1) for all atrial flutter episodes and decreased significantly when increasing AF complexity as defined by Wells (type I: /spl rho/=0.75/spl plusmn/0.23; type II: /spl rho/=0.35/spl plusmn/0.11; type III: /spl rho/=0.15/spl plusmn/0.08; P<0.01). The ability to distinguish different AF episodes was assessed by designing a classification scheme based on a minimum distance analysis, obtaining an accuracy of 85.5%. The algorithm was able to discriminate among AF types even in presence of few depolarizations as no significant /spl rho/ changes were observed by reducing the signal length down to include five LAWs. Finally, the capability to detect transient instances of AF complexity and to map the local regularity over the atrial surface was addressed by the dynamic and multisite evaluation of /spl rho/, suggesting that our algorithm could improve the understanding of AF mechanisms and become useful for its clinical treatment.

Multiphoton multifocal microscopy exploiting a diffractive optical element

Multiphoton multifocal microscopy (MMM) usually has been achieved through a combination of galvo scanners with microlens arrays, with rotating disks of microlens arrays, and cascaded beam splitters with asynchronous rastering of scanning mirrors. Here we describe the achievement of a neat and compact MMM by use of a high-diffraction-efficiency diffractive-optic element that generates a multiple-spot grid of uniform intensity to achieve higher fidelity in imaging of live cells at adequate speeds.

Combined intracellular three-dimensional imaging and selective nanosurgery by a nonlinear microscope.

We use near-IR femtosecond laser pulses for a combination of microscopy and nanosurgery on fluorescently labeled structures within living cells. Three-dimensional reconstructions of microtubule structures tagged with green fluorescent protein (GFP) are made during different phases of the cell cycle. Further, the microtubules are dissected using the same laser beam but with a higher laser power than for microscopy. We establish the viability of this technique for the cells of a fission yeast, which is a common model to study the mechanics of cell division. We show that nanosurgery can be performed with submicrometer precision and without visible collateral damage to the cell. The energy is primarily absorbed by the GFP molecules, and not by other native structures in the cell. GFP is particularly suitable for multiphoton excitation, as its excitation wavelength near 900 nm is benign for most cellular structures. The ability to use GFP to label structures for destruction by multiphoton excitation may be a valuable tool in cell biology.

Complex dynamics underlying the human electrocardiogram

Sequences of different human cardiac rhythms terminating in ventricular fibrillation have been studied, both qualitatively and quantitively, with methods of nonlinear dynamics. The analysis has been applied to ECG epochs belonging to rhythms of increasing electrocardiographic irregularity: from sinus rhythm to prefibrillatory rhythms and then to ventricular fibrillation. The phase portraits of these rhythms have been reconstructed from the ECG recording with the time-delay technique, and their correlation dimensions have been estimated with the algorithm of Grassberger and Procaccia (1983a, b). Different cardiac rhythms exhibit different correlation dimensions that describe the corresponding degrees of complexity. The correlation dimension increases as one proceeds from sinus rhythm to fully developed ventricular fibrillation via intermediate rhythms. The fully developed ventricular fibrillation shows the highest degree of complexity. The dimensional analysis supports the existence of complex dynamics underlying different cardiac rhythms and reveals an increase in dimensional complexity corresponding to an increase in electrocardiographic irregularity. Our results indicate that nonlinear dynamics may be used to assess various dynamic states of the heart and may offer a non-invasive tool to investigate the complex dynamic phenomena occuring during arrhythmia.

Different patterns of atrial activation in idiopathic atrial fibrillation: simultaneous multisite atrial mapping in patients with paroxysmal and chronic atrial fibrillation

OBJECTIVES We aimed to evaluate: 1) the behavior of electrical activity simultaneously in different atrial regions during atrial fibrillation (AF); 2) the difference of atrial activation between paroxysmal and chronic AF; 3) the atrial refractoriness dispersion; and 4) the correlation between the effective refractory periods (ERPs) and the FF intervals. BACKGROUND Little data exist on the electrophysiologic characteristics of the different atrial regions in patients with AF. A more detailed knowledge of the electrical activity during AF may provide further insights to improve treatment of AF. METHODS Right and left atria were extensively mapped in 30 patients with idiopathic AF (18 paroxysmal and 12 chronic). In different atrial locations, we analyzed 1) the FF interval duration; and 2) the grade of organization and, in case of organized electrical activity, the direction of atrial activation. Furthermore, in patients with paroxysmal AF, we determined the atrial ERP, evaluated the ERP dispersion and assessed the presence of a correlation between the ERPs and the FF intervals. RESULTS In patients with chronic AF, we observed a shortening of the FF intervals and a greater prevalence of disorganized activity in all the atrial sites examined. In patients with paroxysmal AF, a significant dispersion of refractoriness was observed. The right lateral wall showed longer FF intervals and more organized atrial activity and, unexpectedly, the shortest mean ERPs. In contrast, the septal area showed shorter FF intervals, greater disorganization and the longest mean ERPs. CONCLUSIONS Electrical activity during AF showed a significant spatial inhomogeneity, which was more evident in patients with paroxysmal AF. The mean FF intervals did not correlate with the mean ERPs.

Anticancer drug delivery system based on calcium carbonate particles loaded with a photosensitizer.

In photodynamic therapy (PDT), photosensitizers are required to arrive in high concentrations at selective targets like cancer cells avoiding toxicity in healthy tissue. In this work, we propose the application of porous calcium carbonate carriers in the form of polycrystalline vaterite for this task. We investigated the loading efficiency for the photosensitizer Photosens in vaterite micro- and nanocarriers. A possible release mechanism depending on the surrounding pH was studied, showing a fast degradation of the carriers in buffers below pH7. These results hold out the prospect of a novel PDT drug delivery system. Variation of particle size or additional coatings allow custom-design of workload release curves. An intrinsic cancer-sensitivity can be expected from the pH-dependent release in the acidic microenvironment of cancer tissue.

Causal transfer function analysis to describe closed loop interactions between cardiovascular and cardiorespiratory variability signals

Abstract.Although the concept of transfer function is intrinsically related to an input–output relationship, the traditional and widely used estimation method merges both feedback and feedforward interactions between the two analyzed signals. This limitation may endanger the reliability of transfer function analysis in biological systems characterized by closed loop interactions. In this study, a method for estimating the transfer function between closed loop interacting signals was proposed and validated in the field of cardiovascular and cardiorespiratory variability. The two analyzed signals x and y were described by a bivariate autoregressive model, and the causal transfer function from x to y was estimated after imposing causality by setting to zero the model coefficients representative of the reverse effects from y to x. The method was tested in simulations reproducing linear open and closed loop interactions, showing a better adherence of the causal transfer function to the theoretical curves with respect to the traditional approach in presence of non-negligible reverse effects. It was then applied in ten healthy young subjects to characterize the transfer functions from respiration to heart period (RR interval) and to systolic arterial pressure (SAP), and from SAP to RR interval. In the first two cases, the causal and non-causal transfer function estimates were comparable, indicating that respiration, acting as exogenous signal, sets an open loop relationship upon SAP and RR interval. On the contrary, causal and traditional transfer functions from SAP to RR were significantly different, suggesting the presence of a considerable influence on the opposite causal direction. Thus, the proposed causal approach seems to be appropriate for the estimation of parameters, like the gain and the phase lag from SAP to RR interval, which have a large clinical and physiological relevance.

Performance assessment of standard algorithms for dynamic R-T interval measurement: comparison between R-Tapex and R-Tend approach

Three automatic approaches to ventricular repolarisation duration measurement (R-Tapex, R-Tend threshold and R-Tend fitting methods) are compared on computer-generated and real ECG signals, in relation to their reliability in the presence of the most common electrocardiographic artefacts (i.e. additive broadband noise and additive and multiplicative periodical disturbances). Simulations permit the evaluation of the amount of R-T beat-to-beat variability induced by the artefacts. The R-Tend threshold method performs better than the R-Tend fitting one, and, hence, the latter should be used with caution when R-Tend variability is addressed. Whereas the R-Tapex method is more robust with regard to broadband noise than the R-Tend threshold one, the reverse situation is observed in the presence of periodical amplitude modulations. A high level of broadband noise does not prevent the detection of the central frequency of underlying R-T periodical changes. Comparison between the power spectra of the beat-to-beat R-T variability series obtained from three orthogonal ECG leads (X,Y,Z) is used to assess the amount of real and artefactual variability in 13 normal subjects at rest. The R-Tapex series displays rhythms at high frequency (HF) with a percentage power on the Z lead (57.1±4.9) greater than that on the X and Y leads (41.9±4.6 and 46.1±4.9, respectively), probably because of respiratory-related artefacts affecting the Z lead more remarkably. More uniform HF power distributions over X,Y,Z leads are observed in the R-Tend threshold series (31.8 ±3.8, 39.2±4.1 and 35.1±4.2, respectively), thus suggesting minor sensitivity of the R-Tend threshold measure to respiratory-related artefacts.

Spontaneous beat-to-beat variability of the ventricular repolarization duration

The spontaneous beat-to-beat variability of the ventricular repolarization duration was investigated in 21 healthy subjects (age 25-71 years; mean, 40 years) during the basal state in a recumbent position. For each subject, approximately 1,000 consecutive cycles were analyzed with an automated technique. The time series of the RR, QT, and RT intervals generate histograms that approximate normal distributions and have mean standard deviations of 57.0 ms, 5.4 ms, and 4.3 ms, respectively. Spectral analysis was used to detect rhythmical oscillations in these time series. The power spectra densities of both heart rate and ventricular repolarization during show peaks in the same frequency bands: low frequency (0.05-0.12 Hz) and high frequency (0.2-0.4 Hz). The power distribution between these two bands observed in the ventricular repolarization duration spectra was found to be the reverse of that in heart rate spectra (p less than 0.005).

Quantification of synchronization during atrial fibrillation by Shannon entropy: Validation in patients and computer model of atrial arrhythmias

Atrial fibrillation (AF), a cardiac arrhythmia classically described as completely desynchronized, is now known to show a certain amount of synchronized electrical activity. In the present work a new method for quantifying the level of synchronization of the electrical activity recorded in pairs of atrial sites during atrial fibrillation is presented. A synchronization index (Sy) was defined by quantifying the degree of complexity of the distribution of the time delays between sites by Shannon entropy estimation. The capability of Sy to discriminate different AF types in patients was assessed on a database of 60 pairs of endocardial recordings from a multipolar basket catheter. The analysis showed a progressive and significant decrease of Sy with increasing AF complexity classes as defined by Wells (AF type I Sy = 0.73 +/- 0.07, type II Sy = 0.56 +/- 0.07, type III Sy = 0.36 +/- 0.04, p < 0.001). The extension of Sy calculation to the whole right atrium showed the existence of spatial heterogeneities in the synchronization level. Moreover, experiments simulated by a computer model of atrial arrhythmias showed that propagation patterns with different complexity could be the basis of different synchronization levels found in patients. In conclusion the quantification of synchronization by Shannon entropy estimation of time delay dispersion may facilitate the identification of different propagation patterns associated with AF, thus enhancing our understanding of AF mechanisms and helping in its treatment.