Papers by Alessandro Cristoforetti
International Journal of Environmental Research and Public Health, 2022
Face masking proved essential to reduce transmission of COVID-19 and other respiratory infections... more Face masking proved essential to reduce transmission of COVID-19 and other respiratory infections in indoor environments, but standards and literature do not provide simple quantitative methods for quantifying air leakage at the face seal. This study reports an original method to quantify outward leakage and how wearing style impacts on leaks and filtration efficiency. The amount of air leakage was evaluated on four medical masks and four barrier face coverings, exploiting a theoretical model and an instrumented dummy head in a range of airflows between 30 and 160 L/min. The fraction of air leaking at the face seal of the medical masks and barrier face coverings ranged from 43% to 95% of exhaled air at 30 L/min and reduced to 10–85% at 160 L/min. Filter breathability was the main driver affecting both leak fraction and total filtration efficiency that varied from 5% to 53% and from 15% to 84% at 30 and 160 L/min, respectively. Minor changes were related to wearing style, supporting ...
Frontiers in Physiology, 2021
The expanding role of catheter ablation of atrial fibrillation (AF) has stimulated the developmen... more The expanding role of catheter ablation of atrial fibrillation (AF) has stimulated the development of novel mapping strategies to guide the procedure. We introduce a novel approach to characterize wave propagation and identify AF focal drivers from multipolar mapping data. The method reconstructs continuous activation patterns in the mapping area by a radial basis function (RBF) interpolation of multisite activation time series. Velocity vector fields are analytically determined, and the vector field divergence is used as a marker of focal drivers. The method was validated in a tissue patch cellular automaton model and in an anatomically realistic left atrial (LA) model with Courtemanche–Ramirez–Nattel ionic dynamics. Divergence analysis was effective in identifying focal drivers in a complex simulated AF pattern. Localization was reliable even with consistent reduction (47%) in the number of mapping points and in the presence of activation time misdetections (noise <10% of the c...
Journal of Cardiovascular Medicine, 2016
Aims Heterozygous p.(Ser64Arg) mutation in the natriuretic peptide precursor A gene has been asso... more Aims Heterozygous p.(Ser64Arg) mutation in the natriuretic peptide precursor A gene has been associated with atrial fibrillation in the presence of common single nucleotide polymorphisms (rs10033464 and rs2200733; 4q25) that would act as modifiers. Methods We screened natriuretic peptide precursor A gene in 583 individuals and identified three unrelated carriers of the p.(Ser64Arg) mutation (0.5%). Results Only one of the three mutation carriers had episodes of atrial fibrillation. Cascade screening of the three families identified seven additional mutation carriers, none showing atrial fibrillation. The patients with atrial fibrillation also carried the rs2200733, which was however found in four additional nonatrial fibrillation family members and carriers of the p.(Ser64Arg). The prevalence of atrial fibrillation in p.(Ser64Arg) carriers was 10% and in those combining the mutation with the risk single nucleotide polymorphisms was 20%. In the unique mutated patient with atrial fibrillation, the arrhythmias was refractory to both pharmacological and ablation treatment, during 16 years of follow-up; his electrophysiological phenotype was characterized by short atrial cycle lengths with a median value of 131 ms that suggests shortening of atrial action potential. Conclusion The prevalence of p.(Ser64Arg) mutation is low in the general population as is the prevalence of atrial fibrillation in mutation carriers (1/10). Atrial fibrillation in the affected mutated patient was lone at onset and progressively evolved with peculiar electrophysiological patterns.
Computers in Cardiology, 2004
This study aims to extract the interior surface of the left atrium (LA) and pulmonary veins (PVs)... more This study aims to extract the interior surface of the left atrium (LA) and pulmonary veins (PVs) from threedimensional tomographic data and to integrate it with LA CARTO electrical maps. The separation of LA and PVs from other overlapping structures of the heart was performed processing 3D CT data by markercontrolled watershed segmentation and surface extraction. CARTO maps were then registered on the L A internal surface by a stochastic optimization algorithm based on simulated annealing. The residual registration error resulted inferior to 3 mm. The integration between electrophysiological and high resolved anatomic information of LA results feasible and may constitute a significant support for mechanism investigation and treatment of atrial fibrillation.
Progress in biophysics and molecular biology, 2014
The identification of suitable markers for critical patterns during atrial fibrillation (AF) may ... more The identification of suitable markers for critical patterns during atrial fibrillation (AF) may be crucial to guide an effective ablation treatment. Single parameter maps, based on dominant frequency and complex fractionated electrograms, have been proposed as a tool for electrogram-guided ablation, however the specificity of these markers is debated. Experimental studies suggest that AF critical patterns may be identified on the basis of specific rate and organization features, where rapid organized and rapid fragmented activities characterize respectively localized sources and critical substrates. In this paper we introduce the logical operator map, a novel mapping tool for a point-by-point identification and localization of AF critical sites. Based on advanced signal and image processing techniques, the approach combines in a single map electrogram-derived rate and organization features with tomographic anatomical detail. The construction of the anatomically-detailed logical ope...
Clinical Applications of Cardiac CT, 2012
ABSTRACT In the field of noncoronary applications of cardiac CT the study of the cardiac and pulm... more ABSTRACT In the field of noncoronary applications of cardiac CT the study of the cardiac and pulmonary veins is of great use for the cardiologist, the former particularly in patients with heart failure who require electrical resynchronization of the cardiac chambers (cardiac resynchronization therapy or biventricular pacing) and the latter in patients scheduled to undergo a catheter ablation procedure. Noninvasive cardiac imaging has the task of compiling an anatomic roadmap to render the interventional procedures more effective and efficient. Unlike the study of the coronary arteries, the aim is not to detect disease, but rather to accurately outline the regional anatomy, an objective which can be achieved thanks to the elevated spatial and temporal resolution of multidetector computed tomography (MDCT).
Medical Engineering & Physics, 2008
The delineation of left atrium (LA) and pulmonary veins (PVs) anatomy from high resolution images... more The delineation of left atrium (LA) and pulmonary veins (PVs) anatomy from high resolution images holds importance for atrial fibrillation (AF) investigation and treatment. In this study, a semiautomatic segmentation procedure for LA and PVs inner surface from contrast enhanced CT data was developed. The procedure consists of a three dimensional marker controlled watershed segmentation applied to the external morphological gradient, followed by variable threshold surface extraction from the original intensity image. A preliminary anisotropic non-linear filtering was implemented to improve the S/N ratio of CT images. The performance of segmentation was evaluated on cardiac CT scans of 12 AF patients both qualitatively and quantitatively. The qualitative evaluation by expert radiologist assessed the segmentation as overall successful in all patients and capable of extracting both the LA body and the connected vascular trees. The quantitative validation, by computing discrepancy measures with respect to a manually segmented gold standard, indicated an average of about 90% of voxels correctly classified and an average border mismatch lower than 1.5 voxels (1.2 mm). The accurate extraction of the inner LA-PVs walls provided by this method, along with the minimal required human intervention, should facilitate the use of anatomical atrial models for the non-pharmacological treatment of AF.
IEEE Transactions on Biomedical Engineering, 2013
Biophysically detailed and anatomically realistic atrial models are emerging as a valuable tool i... more Biophysically detailed and anatomically realistic atrial models are emerging as a valuable tool in the study of atrial arrhythmias, nevertheless clinical use of these models would be favored by a reduction of computational times. This paper introduces a novel adaptive mesh algorithm, based on multiresolution representation (MR), for the efficient integration of cardiac ordinary differential equation (ODE)-partial differential equation (PDE) systems on unstructured triangle meshes. The algorithm applies a dynamically adapted node-centered finite volume method (FVM) scheme for integration of diffusion. The method accuracy and efficiency were evaluated by simulating propagation scenarios of increasing complexity levels (pacing, stable spirals, atrial fibrillation) on tomography-derived three-dimensional monolayer atrial models, based on a monodomain reaction-diffusion formulation coupled with the Courtemanche atrial ionic model. All simulated propagation patterns were accurately reproduced with substantially reduced computational times (10%-30% of the full-resolution simulation time). The proposed algorithm, combining the MR computational efficiency with the geometrical flexibility of unstructured meshes, may favor the development of patient-specific multiscale models of atrial arrhythmias and their application in the clinical setting.
European Heart Journal, 2005
peptides as markers of mild forms of left ventricular dysfunction: effects of assays on diagnosti... more peptides as markers of mild forms of left ventricular dysfunction: effects of assays on diagnostic performance of markers.
2020 IEEE 20th Mediterranean Electrotechnical Conference ( MELECON), 2020
Motion coordination between the operating table and imaging or surgical devices is becoming incre... more Motion coordination between the operating table and imaging or surgical devices is becoming increasingly relevant for minimally invasive procedures in the hybrid operating room. In this paper, we presented a mathematical framework for the generation of a virtual remote center of motion (RCM) for a 5 degrees-of-freedom (DOFs) motorized surgical table. The capability of the table to synchronize its orientation to a rotating paired medical device was also addressed. The table inverse kinematic problem was solved by efficient algorithms, which were tested in a virtual simulation environment using a parametrized table model. The proposed solutions support arbitrary RCM position and can be adapted to different 5-DOFs table models by parameter tuning.
Circulation, 2000
Background-The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers... more Background-The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. Methods and Results-We selected 26 patients with resistant AF, either paroxysmal (nϭ14) or permanent (nϭ12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for Ն6 months. Procedures lasted 290Ϯ58 minutes, including 80Ϯ22 minutes for acquisition of all maps, and 118Ϯ16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0.08Ϯ0.02 mV) inside the circular line and by disparity in activation times (58Ϯ11 ms) across the lesion. After 9Ϯ3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (PϭNS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. Conclusions-Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.
comparison between muki-slice computed tomography (MSCT) and intracardiac echocardiography (ICE).... more comparison between muki-slice computed tomography (MSCT) and intracardiac echocardiography (ICE). Methods: the PV and their atrial insertion were evaluated in 42 patients (35 men, 494-9 years) admitted for ablation of PV ostia. Ostia were measured in 2 directions (anterior-posterior (AP) and superior-inferior (SI)) with MSCT. 2-D measurements of PV ostia were performed with ICE. Resuks were compared, considering MSCT as the gold standard. Venous ostium indexes were calculated by dividing MSCT-measurements in AP-direction and SI-direction. Results: common ostia of left PV were observed in 33(79%) patients with MS CT and 31 (74%) patients with ICE. Common ostia of right PV were observed in 13(31%) and 16(38%) patients, respectively. Additional PV were observed in 13(31%) patients with MSCT and in 7(17%) patients with ICE. Ostial diameters by MSCT in AP-direction were similar to 2-D measurements by ICE. By contrast, diameters by MSCT in SI-direction were significantly larger than 2-D diameters measured with ICE. Venous ostium indexes were 0.774-0.18 and 0.904-0.15 (p<0.01) for left and right PV respectively, indicating an oval shape of particularly left PV ostia. Conclusions: variation in PV anatomy is frequently observed with both techniques. The sensitivity for detection of additional branches is higher for MSCT. Resuks of measurements of PV ostia suggest an underestimation of ostial size by ICE. 3-D imaging techniques, such as MSCT, are required to demonstrate an oval shape of PV ostia. 943 Usefulness of a non fluoroscopic navigation system during ectopic atrial tachycardia RF ablation
Quantitative MRI has potential for tissue characterization after reparative and regenerative surg... more Quantitative MRI has potential for tissue characterization after reparative and regenerative surgical treatment of osteochondral lesions of the talus (OCLTs). However available data is inconclusive and quantitative sequences can be difficult to implement in real‐time clinical application.
Computers in Biology and Medicine
Intraoral autologous bone grafting represents a preferential choice for alveolar reconstruction p... more Intraoral autologous bone grafting represents a preferential choice for alveolar reconstruction prior to dental implant placement. Bone block harvesting guided by a computer-planned lithographic template is a novel and promising technique for optimizing the volume of harvested material, while controlling the osteotomy 3D position with respect to delicate anatomical structures. We provide a quantitative framework to non-invasively estimate the accuracy of this technique. In the proposed framework, the planned osteotomy geometry was compared to the real outcome of the procedure, obtained by segmentation of post-procedural cone beam computed tomography data. The comparison required the rigid registration between pre and post-procedural mandibular models, which was automatically accomplished by minimizing the sum of squared distances via a stochastic multi-trial iterative closest point algorithm. Bone harvesting accuracy was quantified by calculating a set of angular and displacement errors between the planned and real planes which characterized the excision block. The application of the framework to four cases showed its capability to quantify the tolerance associated with computer-guided bone harvesting techniques with submillimetric accuracy (<0.4 mm), within the limits of native image resolution. The validation methodology proved suitable for defining the safety margins of osteotomy surgical planning.
Physics in Medicine & Biology
The success of transcatheter aortic valve implantation (TAVI) is highly dependent on the predicti... more The success of transcatheter aortic valve implantation (TAVI) is highly dependent on the prediction of the interaction between the prosthesis and the aortic root anatomy. The simulation of the surgical procedure may be useful to guide artificial valve selection and delivery, nevertheless the introduction of simulation models into the clinical workflow is often hindered by model complexity and computational burden. To address this point, we introduced a patient-specific mass-spring model (MSM) with viscous damping, as a good trade-off between simulation accuracy and time-efficiency. The anatomical model consisted of a hexahedral mesh, segmented from pre-procedural patient-specific cardiac computer tomographic (CT) images of the aortic root, including valve leaflets and attached calcifications. Nodal forces were represented by linear-elastic springs acting on edges and angles. A fast integration approach based on the modulation of nodal masses was also tested. The model was validated on seven patients, comparing simulation results with post-procedural CT images with respect to calcification and aortic wall position. The validation showed that the MSM was able to predict calcification displacement with an average accuracy of 1.72 mm and 1.54 mm for the normal and fast integration approaches, respectively. Wall displacement root mean squared error after valve expansion was about 1 mm for both approaches, showing an improved matching with respect to the pre-procedural configuration. In terms of computational burden, the fast integration approach allowed a consistent reduction of the computational times, which decreased from 36 h to 21.8 min per 100 K hexahedra. Our findings suggest that the proposed linear-elastic MSM model may provide good accuracy and reduced computational times for TAVI simulations, fostering its inclusion in clinical routines.
IEEE Transactions on Biomedical Engineering, 2016
This study introduces a predictability framework based on the concept of Granger causality (GC), ... more This study introduces a predictability framework based on the concept of Granger causality (GC), in order to analyze the activity and interactions between different intracardiac sites during atrial fibrillation (AF). Methods: GC-based interactions were studied using a three-electrode analysis scheme with multi-variate auto-regressive models of the involved preprocessed intracardiac signals. The method was evaluated in different scenarios covering simulations of complex atrial activity as well as endocardial signals acquired from patients. Results: The results illustrate the ability of the method to determine atrial rhythm complexity and to track and map propagation during AF. Conclusion: The proposed framework provides information on the underlying activation and regularity , does not require activation detection or post-processing algorithms and is applicable for the analysis of any mul-ti-electrode catheter. Significance: The proposed framework can potentially help to guide catheter ablation interventions of AF.
2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2015
The assessment of collagen structure in cardiac pathology, such as atrial fibrillation (AF), is e... more The assessment of collagen structure in cardiac pathology, such as atrial fibrillation (AF), is essential for a complete understanding of the disease. This paper introduces a novel methodology for the quantitative description of collagen network properties, based on the combination of nonlinear optical microscopy with a spectral approach of image processing and analysis. Second-harmonic generation (SHG) microscopy was applied to atrial tissue samples from cardiac surgery patients, providing label-free, selective visualization of the collagen structure. The spectral analysis framework, based on 2D-FFT, was applied to the SHG images, yielding a multiparametric description of collagen fiber orientation (angle and anisotropy indexes) and texture scale (dominant wavelength and peak dispersion indexes). The proof-of-concept application of the methodology showed the capability of our approach to detect and quantify differences in the structural properties of the collagen network in AF versus sinus rhythm patients. These results suggest the potential of our approach in the assessment of collagen properties in cardiac pathologies related to a fibrotic structural component.
ABSTRACT Atrial fibrillation (AF) is the most common complication of cardiac surgery intervention... more ABSTRACT Atrial fibrillation (AF) is the most common complication of cardiac surgery interventions. Several mechanisms are involved in the occurrence of this complex arrhythmia, which include electrical and structural remodeling. In particular, it has been shown that atrial fibrosis, which consists in the massive accumulation of the extracellular matrix (ECM) components between cardiomyocytes, may interfere with the electrical impulse propagation creating a substrate for AF. As well, microRNAs (miRNAs), a broad class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, have been recently indicated as regulators of diverse cardiovascular functions, which may potentially affect arrhythmia occurrence. This study investigates the molecular and structural features of atrial tissue biopsies obtained from patients undergoing cardiac surgery, aiming to identify potential correlations with the occurrence of AF. Specifically, the total RNA was extracted from small biopsies of the right atrial appendage, and the expression of a set of miRNAs, known to regulate structural proteins / ion channels, was evaluated by qRT-PCR. Concurrently, the total collagen content was assessed by applying histological techniques and polarized microscopy to Picro Sirius Red stained tissue slices. The analysis revealed specific profiles of fibrosis-related microRNAs and intramural fibrosis distribution in AF patients, suggesting the potential role of post-transcriptional regulation mechanisms in the creation of a pro-arrhythmic substrate.
Journal of Cardiovascular Electrophysiology, 2014
Although atrial arrhythmias may have genetic causes, very few data are available on evaluation of... more Although atrial arrhythmias may have genetic causes, very few data are available on evaluation of the arrhythmic substrate in genetic atrial diseases in humans. In this study, we evaluate the nature and evolution of the atrial arrhythmic substrate in a genetic atrial cardiomyopathy. Repeated electroanatomic mapping and tomographic evaluations were used to investigate the evolving arrhythmic substrate in 5 patients with isolated arrhythmogenic atrial cardiomyopathy, caused by Natriuretic Peptide Precursor A (NPPA) gene mutation. Atrial fibrosis was assessed using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). The substrate of atrial tachycardia (AT) and atrial fibrillation (AF) was biatrial dilatation with patchy areas of low voltage and atrial wall scarring (in the right atrium: 68.5% ± 6.0% and 22.2% ± 10.2%, respectively). The evolution of the arrhythmic patterns to sinus node disease with atrial standstill (AS) was associated with giant atria with extensive low voltage and atrial scarring areas (in the right atrium: 99.5% ± 0.7% and 57.5% ± 33.2%, respectively). LGE-MRI-proven biatrial fibrosis (Utah stage IV) was associated with AS. Atrial conduction was slow and heterogeneous, with lines of conduction blocks. The progressive extension and spatial distribution of the scarring/fibrosis were strictly associated with the different types of arrhythmias. The evolution of the amount and distribution of atrial scarring/fibrosis constitutes the structural substrate for the different types of atrial arrhythmias in a pure genetic model of arrhythmogenic atrial cardiomyopathy.
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Papers by Alessandro Cristoforetti