Neutralisation of myoelectric interference from recorded nerve signals using models of the electrode impedance

Any form of paralysis due to spinal cord injury or other medical condition, can have a significant impact on the quality and life expectancy of an individual. Advances in medicine and surgery have offered solutions that can improve the condition of a patient, however, most of the times an individual’s life does not dramatically improve. Implanted neuroprosthetic devices can partially restore the lost functionalities by means of functional electrical stimulation techniques. This involves applying patterns of electrical current pulses to innervate the neural pathways between the brain and the affected muscles/organs, while recording of neural information from peripheral nerves can be used as feedback to improve performance. Recording naturally occurring nerve signals via implanted electrodes attached to tripolar amplifier configurations is an approach that has been successfully used for obtaining desired information in non-acute preparations since the mid-70s. The neural signal (i.e. ENG), which can be exploited as feedback to another system (e.g. a stimulator), or simply extracted for further processing, is then intrinsically more reliable in comparison to signals obtained by artificial sensors. Sadly, neural recording of this type can be greatly compromised by myoelectric (i.e. EMG) interference, which is present at the neural interface and registered by the recording amplifier. Although current amplifier configurations reduce myoelectric interference this is suboptimal and therefore there is room for improvement. The main difficulty exists in the frequency-dependence of the electrode-tissue interface impedance which is complex. The simplistic Quasi-Tripole amplifier configuration does not allow for the complete removal of interference but it is the most power efficient because it uses only one instrumentation amplifier. Conversely, the True-Tripole and its developed automatic counterpart the Adaptive-Tripole, although minimise interference and provide means of compensating for the electrode asymmetries and changes that occur to the neural interface (e.g. due to tissue growth), they do not remove interference completely as the insignificant electrode impedance is still important. Additionally, removing interference apart from being dependent on the frequency of the interfering source, it is also subject to its proximity and orientation with respect to the recording electrodes, as this affects the field. Hence neutralisation with those two configurations, in reality, is not achieved in the entire bandwidth of the neural signal in the interfering spectrum. As both are less power efficient than the Quasi-Tripole an alternative configuration offering better performance in terms of interference neutralisation (i.e. frequency-independent, insensitive to the external interference fields) and, if possible, consume less power, is considered highly attractive. The motivation of this work is based on the following fact: as there are models that can mimic the frequency response of metal electrodes it should be possible, by constructing a network of an equivalent arrangement to the impedance of electrodes, to fit the characteristic neutralisation impedance – the impedance needed to balance a recording tripole – and ideally require no adjustment for removing interference. The validity of this postulation is proven in a series of in-vitro preparations using a modified version of the Quasi-Tripole made out of discrete circuit components where an impedance is placed at either side of the outer electrodes for balancing the recording arrangement. Various models were used in place of that impedance. In particular, representing the neutralisation impedance as a parallel RC reduced interference by a factor of 10 at all frequencies in the bandwidth of the neural signal while removed it completely at a spot frequency. Conversely, modelling the effect of the constant phase angle impedance of highly polarisable electrodes using a 20 stages non-uniform RC ladder network resulted in the minimisation of interference without the initial requirement of continuous adjustment. It is demonstrated that with a model that does not perfectly fit the impedance profile of a monopolar electrochemical cell an average reduction in interference of about 100 times is achieved, with the cell arranged as a Wheatstone bridge that can be balanced in the ENG band

Development of techniques for time-lapse imaging of the dynamics of glial-axonal interactions in the central nervous system

Background: Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualise the various stages of myelination. Methodology/Principal findings: Two approaches have been taken to follow myelination over time i) time-lapse imaging of mixed CNS myelinating cultures generated from mouse spinal cord to which exogenous GFP-labelled murine cells were added, and ii) ex vivo imaging of the spinal cord of shiverer (Mbp mutant) mice, transplanted with GFP-labelled murine neurospheres. The data demonstrate that oligodendrocyte-axonal interactions are dynamic events with continuous retraction and extension of oligodendroglial processes. Using cytoplasmic and membrane-GFP labelled cells to examine different components of the myelin-like sheath, evidence from time-lapse fluorescence microscopy and confocal microscopy suggest that the oligodendrocytes’ cytoplasm-filled processes initially spiral around the axon in a corkscrew-like manner. This is followed subsequently by focal expansion of the corkscrew process to form short cuffs which then extend longitudinally along the axons. From this model it is predicted that these spiral cuffs must extend over each other first before extending to form internodes of myelin. Conclusion: These experiments show the feasibility of visualising the dynamics of glial-axonal interaction during myelination over time. Moreover, these approaches complement each other with the in vitro approach allowing visualisation of an entire internodal length of myelin and the ex vivo approach validating the in vitro data

The transformative nature of networks within contemporary art practice

Since the introduction of the World Wide Web in 1991, it has had a significant impact on contemporary art. As a consequence, however, networks are almost exclusively considered as technologically determined, art produced is digital, refers to the internet and is more often than not specifically web-based. This research redefines the role of networks in contemporary art. It proposes that networks are not a specific technology that provides a means for art practice to occur but are a concept that transforms practice and enables a networked art. Networked art is a continuation of twentieth century developments in art including cybernetic art, systems aesthetics, new media art and relational aesthetics. The research discusses these and considers how practice became systemised through strategies such as the dematerialization of art as object (Lippard, 1997) and the renouncement of objecthood (Fried, 1998). Equally important is the emergence of cybernetics and systems theory that explained concepts such as process and behaviour frequently employed in art practice. By defining a network as a type of system, networked art is foremost concerned with connections or links and considers the resulting behaviours that occur. Networked art is therefore not centred on networks as form. It can adapt as technologies evolve over time and as such is considered post specific technologies and the disciplines connected with them

Mitochondrial function and dynamics in demyelinated axons

Demyelination is a pathological process which causes profound changes in the physiology of axons. Post mortem evidence suggests that mitochondrial content is increased in demyelinated axons which has led to the widely accepted theory that loss of myelin causes an increase in axonal energy demand which in turn can be satisfied by a larger number of mitochondria. However, demyelinated axons are known to undergo a series of changes from conduction block early on in demyelination to altered modes of conduction and finally remyelination and return of normal conduction. Little is known about how these different states influence axonal mitochondria. In this thesis, mitochondrial function and dynamics were investigated throughout the time course of lysolecithin-mediated de- and remyelination in the saphenous nerve in vivo. First, the time course of anatomical and electrophysiological changes after application of lysolecithin was mapped out using semi-thin resin sections and recordings of compound action potentials. Then, mitochondrial dynamics and membrane potential were measured at various time points during the onset and resolution of demyelination. Mitochondrial transport was significantly reduced during the first week of demyelination, preceding the accumulation of stationary mitochondria in the axon. At the same time, mitochondrial membrane potential was significantly increased, particularly at the earliest time points investigated (days 2 and 4). Interestingly, all changes including the abovementioned accumulation of mitochondria took place before the return of conduction and putative increase in energy demand. In order to understand better the processes underlying these changes, the role of two known modifiers of mitochondrial dynamics were investigated: action potential conduction and intra-axonal calcium. A 6h conduction block was induced using bupivacaine and confirmed using electrophysiological stimulation but did not lead to any of the changes seen in the early phases of demyelination. On the other hand, calcium imaging using the genetically encoded calcium sensor Tn-XXL revealed a slight but consistent increase in intra-axonal calcium in demyelinated axons, both at the time point with the highest increase in mitochondrial membrane potential (day 2) and at the time point with the highest mitochondrial density (day 8). Taken together, these findings point to impaired axonal calcium homeostasis, rather than changes in energy demand, as the main driving force behind mitochondrial changes in demyelination. The fact that mitochondrial transport remained impaired until later in the remyelination process may have implications for the long term survival of chronically demyelinated axons

The transformative nature of networks within contemporary art practice

Since the introduction of the World Wide Web in 1991, it has had a significant impact on contemporary art. As a consequence, however, networks are almost exclusively considered as technologically determined, art produced is digital, refers to the internet and is more often than not specifically web-based. This research redefines the role of networks in contemporary art. It proposes that networks are not a specific technology that provides a means for art practice to occur but are a concept that transforms practice and enables a networked art. Networked art is a continuation of twentieth century developments in art including cybernetic art, systems aesthetics, new media art and relational aesthetics. The research discusses these and considers how practice became systemised through strategies such as the dematerialization of art as object (Lippard, 1997) and the renouncement of objecthood (Fried, 1998). Equally important is the emergence of cybernetics and systems theory that explained concepts such as process and behaviour frequently employed in art practice. By defining a network as a type of system, networked art is foremost concerned with connections or links and considers the resulting behaviours that occur. Networked art is therefore not centred on networks as form. It can adapt as technologies evolve over time and as such is considered post specific technologies and the disciplines connected with them. Emerging out of my ongoing art practice this practice-led research makes an original contribution to knowledge in the field of contemporary art in three ways. Firstly, it demonstrates how networks in contemporary art do not have a basis in a specific technology since they have been employed before current technologies. Secondly, the research explains networked art through the development of a framework and practice as research that informs each other. Thirdly, the research discusses emergent processes, themes and content and clarifies how networked art positions itself within current contemporary art discourse as a post-disciplinary practice

Effects of Streptozotocin-Induced Diabetes on gene and protein expression in Sinoatrial node of rat heart

Diabetes mellitus is one of the most common endocrine disorders and its global prevalence is increasing at an alarming rate. Cardiovascular disease is the major cause of morbidity and mortality among diabetic patients. In addition to defects in contraction, the diabetic heart also frequently suffers from disturbances to the electrical conduction system. This study investigates the effects of diabetes on the sinoatrial node (SAN) of the rat heart. Previous in vivo and in vitro experiments have demonstrated reduced heart rate, longer SAN action potential duration, prolonged pacemaker cycle length and Sino-atrial conduction time in streptozotocin (STZ) - induced diabetic rat heart. Thus it is of paramount importance to identify the molecular basis of electrical disturbances in SAN of diabetic heart. The hypothesis is that alterations in mRNA encoding various proteins associated with the generation and transmission of electrical signals in the heart may be responsible for the functional disturbances in the SAN of diabetic heart. Experiments were performed in male Wistar rats 10-12 weeks of age after STZ treatment with a single intraperitoneal injection (60 mg/kg body weight). Heart rate was measured in isolated perfused heart with an extracellular suction electrode. Expression of mRNA encoding a variety of cardiac proteins, involved in electrical transmission, were measured in SAN and right atrial biopsies using real time reverse transcription polymerase reaction technique. Expression of proteins in SAN biopsies was measured using sodium dodecyl sulphate polyacramide gel electrophoresis and Western blotting technique. Ultrastructure of the STZ-SAN was studied using transmission electron microscopy. The heart rate was significantly lower in STZ compared to controls. Of the 85 genes studied, there were some changes of particular interest. These include an increase in the expression of Gja7 (connexin), Cacna1g, Cacna1h, Cacnb3 (calcium channel), Nppa, Nppb (natriuretic peptide) Kcnj5 and Kcnk3 (potassium channel), in STZSAN. There was also decrease in the expression of Scn7a (sodium channel), Kcna2 (potassium channel), a 6-fold decrease in Kcnd2 and a 7-fold decrease in Cacng4. Some of the proteins encoded by these genes showed similar changes in expression including Ryr3, Cav3.1 and Kv4.2 while others like Pro-ANP and BNP did not. The ultrastructure of STZ-SAN had reduced mitochondria. These changes in gene and protein expression may contribute to the electrophysiological disturbances seen in the diabetic SAN. Further studies will be required to investigate whether these changes in mRNA and protein translate into changes in electrophysiological function

TISSUE ENGINEERING CELLULARIZED SILK-BASED LIGAMENT ANALOGUES

The resurgence, and eventual rise to prominence in the field of tissue engineering, that electrospinning has experienced over the last decade speaks to the simplicity and adaptability of the process. Electrospinning has been used for the fabrication of tissue engineering scaffolds intended for use in nearly every part of the human body: blood vessel, cartilage, bone, skin, nerve, connective tissue, etc. Diverse as the aforementioned tissues are in both form and function, electrospinning has found a niche in the repair of each due to its capacity to consistently create non-woven structures of fibers ranging from nano-to-micron size in diameter. These structures have had success in tissue engineering applications because of their ability to mimic the body’s natural structural framework, the extracellular matrix. In this study we examine a number of different techniques for altering scaffold properties (i.e. mechanical strength, degradation rate, permeability, and bioactivity) to create electrospun structures tailored to unique tissue specific applications; the end goal being the creation of a cellularized tissue engineering ligament analogue. To alter the mechanical properties of electrospun structures while maintaining high levels of bioactivity, synthetic polymers such as polydioxanone were blended in solution with naturally occurring proteins like elastin and fibrinogen prior to electrospinning. Cross-linking of electrospun structures, using glutaraldehyde, carbodiimide hydrochloride, and genipin, was also investigated as a means to both improve the mechanical stability and slow the rate of degradation of the structures. Fiber orientation and scaffold anisotropy were controlled through varying fabrication parameters, and proved effective in altering the mechanical properties of the structures. Finally, major changes in the structure of electrospun scaffolds were achieved through the implementation of air-gap electrospinning. Scaffolds created through air-gap electrospinning exhibited higher porosity’s than their traditionally fabricated counterparts, allowing for greater cell penetration into the scaffold. Overall, this collection of results provides insight into the diversity of electrospinning and reveals innumerous options, both pre and post fabrication, for the tissue engineer to create site-specific engineering scaffolds capable of mimicking both the form and function of native tissue

Chitosan based biomaterials: soft tissue engineering applications

In recent years, considerable attention has been given to chitosan (CS)-based biomaterials and their applications in the field of soft tissue engineering (TE). CS is a glycosaminoglycan derived from chitin, the primary structural polymer in crustacean exoskeletons. CS is biocompatible, biodegradable, easily formed into various structures (i.e. sponges, nanofibers and films) under mild processing conditions and can be chemically modified through graft copolymerization and crosslinking. However, the rapid degradation of CS and its low mechanical strength are concerns that may limit its use in clinical applications. In the first part of the thesis, different non cytotoxic crosslinkers were used aiming at improving the structural properties of CS. Genipin (GP), γ-glycidoxypropyltrimethoxysilane (GPTMS), dibasic sodium phosphate (DSP) were selected as biocompatible CS crosslinkers as reported in literature. After a preliminary physico-chemical and mechanical characterization, the proper crosslinking compounds were selected for the development of different typologies of CS scaffolds for both human and veterinary applications. CS- based scaffolds were developed as nerve guidance channels (NGCs) and internal fillers fabrication to promote peripheral nerve regeneration in humans. Two CS based hollow NGCs were prepared and tested in vitro and in vivo (coded as CS flat membrane and bi-layer CS membrane) and a CS based nanostructured internal filler was optimized and characterized in vitro. i. CS flat membranes were prepared by solvent casting. According to the results obtained in the first part of the thesis, DSP alone (CS/DSP) or in association with the GPTMS (CS/GPTMS_DSP) were used as crosslinkers. CS crosslinked membranes showed permeation to nutrients and did not exert any cytotoxic effect on RT4-D6P2T. The higher mechanical stability of CS/GPTMS_DSP under wet state allowed to confirm the RT4-D6P2T attachment and proliferation as well as the neurite outgrowth of dorsal root ganglia (DRG) on CS substrates. Before in vivo implantation in rats, CS/GPTMS_DSP and CS/DSP membranes were easily rolled up to form a NGC. Then, membranes were used to bridge median nerve defects in rats. After 12 week post-operative CS/GPTMS_DSP tubes were found to be detached from the distal suturing site and functional recovery did not occurred. On the other hand, crushed nerve encircled with CS/DSP membranes, allowed nerve fibre regeneration and functional recovery, showing similar results to autografts. ii. Bi-layer CS membranes were developed using a two-step coating technique. CS/DSP and CS/GPTMS_DSP flat membranes were combined to produce scaffold structures with good biocompatibility in the inner layer (CS/DSP) and with the desired mechanical strength imparted by the outer (CS/GPTMS_DSP, GPTMS 25% wt./wt.). Gradual water uptake and permeation to small molecules was observed compared to single layers. From in vivo tests, median nerves treated with bi-layer tubes displayed regenerated and aligned fibres at the injury site. iii. CS crosslinked electrospun nanofibres were fabricated by electrospinning solutions containing CS, polyethylene oxide (PEO), and dimethylsulphoxide (DMSO). PEO and DMSO were introduced to allow the spinnability of CS solutions at high polymer concentration with controllable fiber size and increase fiber yields by relaxing CS chain entanglement. Optimization of the process and solution parameters allowed to obtain CS nanofibres with size of 128±17 nm. To increase CS stability in aqueous media, DSP was used as crosslinker After DSP crosslinking fibre size decreased to 109±17 nm while an increase in the mechanical strength (E, from 63±10 MPa to 113±8 MPa) was observed compared to uncrosslinked nanofibrous matrices. In the third part of the thesis, CS porous membranes with improved antimicrobial properties were prepared for veterinary application. The developed scaffolds were fabricated by freeze-drying to promote the wound healing process and to reduce the bacterial proliferation in chelonian shell injury site. Different ratios of silver nanoparticles (AgNPs, 5%, 10% and 15% wt. /wt.) and gentamicin sulphate (GS, 3.5 mg/ml) were loaded into the CS/GPTMS_DSP membranes to impart the proper antibacterial properties and to favor drug release avoiding the risk of systemic toxicity. After a preliminary in vitro characterization, CS/GPTMS_DSP loaded with AgNPs at a concentration of 10% wt./wt (CS/GPTMS_DSP_AgNP10) was selected as ideal candidate for this application field. GS release profile from CS/GPTMS_DSP_GS evidenced high burst release of the antibiotics in the first day (about 70%). Finally, GS and AgNPs (10 % wt./wt.) effect on bacterial inhibition was evaluated and confirmed against Gram+ and Gram-. The results reported in this thesis work demonstrate that CS is a promising candidate for applications in human and veterinary soft TE. Mechanical and physico-chemical properties of CS scaffolds can be tuned by using different crosslinking methods. By the in vitro characterization, GPTMS and DSP were selected as ideal compounds to the development of scaffolds for peripheral nerve regeneration (in human) and wound healing (in animals). Four different morphologies (3 for peripheral nerve regeneration and 1 for wound healing application) were obtained by varying the fabrication methods and the final composition. All membranes were found to satisfy the requirements for the application of interest. CS based membranes developed for peripheral nerve regeneration were found to be biocompatible, and successful functional recovery was observed in case of CS/DSP and bi-layer membranes. Porous membranes with improved antimicrobial properties were prepared to enhance wound healing in chelonians and were found to be effective against a broad spectrum of bacteria following the release of two different investigated antimicrobial agents (AgNPs and GS)

Novel Cardiac Mapping Approaches and Multimodal Techniques to Unravel Multidomain Dynamics of Complex Arrhythmias Towards a Framework for Translational Mechanistic-Based Therapeutic Strategies

[ES] Las arritmias cardíacas son un problema importante para los sistemas de salud en el mundo desarrollado debido a su alta incidencia y prevalencia a medida que la población envejece. La fibrilación auricular (FA) y la fibrilación ventricular (FV) se encuentran entre las arritmias más complejas observadas en la práctica clínica. Las consecuencias clínicas de tales alteraciones arrítmicas incluyen el desarrollo de eventos cardioembólicos complejos en la FA, y repercusiones dramáticas debido a procesos fibrilatorios sostenidos que amenazan la vida infringiendo daño neurológico tras paro cardíaco por FV, y que pueden provocar la muerte súbita cardíaca (MSC). Sin embargo, a pesar de los avances tecnológicos de las últimas décadas, sus mecanismos intrínsecos se comprenden de forma incompleta y, hasta la fecha, las estrategias terapéuticas carecen de una base mecanicista suficiente y poseen bajas tasas de éxito. Entre los mecanismos implicados en la inducción y perpetuación de arritmias cardíacas, como la FA, se cree que las dinámicas de las fuentes focales y reentrantes de alta frecuencia, en sus diferentes modalidades, son las fuentes primarias que mantienen la arritmia. Sin embargo, se sabe poco sobre los atractores, así como, de la dinámica espacio-temporal de tales fuentes fibrilatorias primarias, específicamente, las fuentes focales o rotacionales dominantes que mantienen la arritmia. Por ello, se ha desarrollado una plataforma computacional, para comprender los factores (activos, pasivos y estructurales) determinantes, y moduladores de dicha dinámica. Esto ha permitido establecer un marco para comprender la compleja dinámica de los rotores con énfasis en sus propiedades deterministas para desarrollar herramientas basadas en los mecanismos para ayuda diagnóstica y terapéutica. Comprender los procesos fibrilatorios es clave para desarrollar marcadores y herramientas fisiológica- y clínicamente relevantes para la ayuda de diagnóstico temprano. Específicamente, las propiedades espectrales y de tiempo-frecuencia de los procesos fibrilatorios han demostrado resaltar el comportamiento determinista principal de los mecanismos intrínsecos subyacentes a las arritmias y el impacto de tales eventos arrítmicos. Esto es especialmente relevante para determinar el pronóstico temprano de los supervivientes comatosos después de un paro cardíaco debido a fibrilación ventricular (FV). Las técnicas de mapeo electrofisiológico, el mapeo eléctrico y óptico cardíaco, han demostrado ser recursos muy valiosos para dar forma a nuevas hipótesis y desarrollar nuevos enfoques mecanicistas y estrategias terapéuticas mejoradas. Esta tecnología permite además el trabajo multidisciplinar entre clínicos y bioingenieros, para el desarrollo y validación de dispositivos y metodologías para identificar biomarcadores multi-dominio que permitan rastrear con precisión la dinámica de las arritmias identificando fuentes dominantes y atractores con alta precisión para ser dianas de estrategias terapeúticas innovadoras. Es por ello que uno de los objetivos fundamentales ha sido la implantación y validación de nuevos sistemas de mapeo en distintas configuraciones que sirvan de plataforma de desarrollo de nuevas estrategias terapeúticas. Aunque el mapeo panorámico es el método principal y más completo para rastrear simultáneamente biomarcadores electrofisiológicos, su adopción por la comunidad científica es limitada principalmente debido al coste elevado de la tecnología. Aprovechando los avances tecnológicos recientes, nos hemos enfocado en desarrollar, y validar, sistemas de mapeo óptico de alta resolución para registro panorámico cardíaco, utilizando modelos clínicamente relevantes para la investigación básica y la bioingeniería.[CA] Les arítmies cardíaques són un problema important per als sistemes de salut del món desenvolupat a causa de la seva alta incidència i prevalença a mesura que la població envelleix. La fibril·lació auricular (FA) i la fibril·lació ventricular (FV), es troben entre les arítmies més complexes observades a la pràctica clínica. Les conseqüències clíniques d'aquests trastorns arítmics inclouen el desenvolupament d'esdeveniments cardioembòlics complexos en FA i repercussions dramàtiques a causa de processos fibril·latoris sostinguts que posen en perill la vida amb danys neurològics posteriors a la FV, que condueixen a una aturada cardíaca i a la mort cardíaca sobtada (SCD). Tanmateix, malgrat els avanços tecnològics de les darreres dècades, els seus mecanismes intrínsecs s'entenen de forma incompleta i, fins a la data, les estratègies terapèutiques no tenen una base mecanicista suficient i tenen baixes taxes d'èxit. La majoria dels avenços en el desenvolupament de biomarcadors òptims i noves estratègies terapèutiques en aquest camp provenen de tècniques valuoses en la investigació de mecanismes d'arítmia. Entre els mecanismes implicats en la inducció i perpetuació de les arítmies cardíaques, es creu que les fonts primàries subjacents a l'arítmia són les fonts focals reingressants d'alta freqüència dinàmica i AF, en les seves diferents modalitats. Tot i això, se sap poc sobre els atractors i la dinàmica espaciotemporal d'aquestes fonts primàries fibril·ladores, específicament les fonts rotacionals o focals dominants que mantenen l'arítmia. Per tant, s'ha desenvolupat una plataforma computacional per entendre determinants actius, passius, estructurals i moduladors d'aquestes dinàmiques. Això va permetre establir un marc per entendre la complexa dinàmica multidomini dels rotors amb ènfasi en les seves propietats deterministes per desenvolupar enfocaments mecanicistes per a l'ajuda i la teràpia diagnòstiques. La comprensió dels processos fibril·latoris és clau per desenvolupar puntuacions i eines rellevants fisiològicament i clínicament per ajudar al diagnòstic precoç. Concretament, les propietats espectrals i de temps-freqüència dels processos fibril·latoris han demostrat destacar un comportament determinista important dels mecanismes intrínsecs subjacents a les arítmies i l'impacte d'aquests esdeveniments arítmics. Mitjançant coneixements previs, processament de senyals, tècniques d'aprenentatge automàtic i anàlisi de dades, es va desenvolupar una puntuació de risc mecanicista a la aturada cardíaca per FV. Les tècniques de cartografia òptica cardíaca i electrofisiològica han demostrat ser recursos inestimables per donar forma a noves hipòtesis i desenvolupar nous enfocaments mecanicistes i estratègies terapèutiques. Aquesta tecnologia ha permès durant molts anys provar noves estratègies terapèutiques farmacològiques o ablatives i desenvolupar mètodes multidominis per fer un seguiment precís de la dinàmica d'arrímies que identifica fonts i atractors dominants. Tot i que el mapatge panoràmic és el mètode principal per al seguiment simultani de paràmetres electrofisiològics, la seva adopció per part de la comunitat multidisciplinària d'investigació cardiovascular està limitada principalment pel cost de la tecnologia. Aprofitant els avenços tecnològics recents, ens centrem en el desenvolupament i la validació de sistemes de mapes òptics de baix cost per a imatges panoràmiques mitjançant models clínicament rellevants per a la investigació bàsica i la bioenginyeria.[EN] Cardiac arrhythmias are a major problem for health systems in the developed world due to their high incidence and prevalence as the population ages. Atrial fibrillation (AF) and ventricular fibrillation (VF), are amongst the most complex arrhythmias seen in the clinical practice. Clinical consequences of such arrhythmic disturbances include developing complex cardio-embolic events in AF, and dramatic repercussions due to sustained life-threatening fibrillatory processes with subsequent neurological damage under VF, leading to cardiac arrest and sudden cardiac death (SCD). However, despite the technological advances in the last decades, their intrinsic mechanisms are incompletely understood, and, to date, therapeutic strategies lack of sufficient mechanistic basis and have low success rates. Most of the progress for developing optimal biomarkers and novel therapeutic strategies in this field has come from valuable techniques in the research of arrhythmia mechanisms. Amongst the mechanisms involved in the induction and perpetuation of cardiac arrhythmias such AF, dynamic high-frequency re-entrant and focal sources, in its different modalities, are thought to be the primary sources underlying the arrhythmia. However, little is known about the attractors and spatiotemporal dynamics of such fibrillatory primary sources, specifically dominant rotational or focal sources maintaining the arrhythmia. Therefore, a computational platform for understanding active, passive and structural determinants, and modulators of such dynamics was developed. This allowed stablishing a framework for understanding the complex multidomain dynamics of rotors with enphasis in their deterministic properties to develop mechanistic approaches for diagnostic aid and therapy. Understanding fibrillatory processes is key to develop physiologically and clinically relevant scores and tools for early diagnostic aid. Specifically, spectral and time-frequency properties of fibrillatory processes have shown to highlight major deterministic behaviour of intrinsic mechanisms underlying the arrhythmias and the impact of such arrhythmic events. Using prior knowledge, signal processing, machine learning techniques and data analytics, we aimed at developing a reliable mechanistic risk-score for comatose survivors of cardiac arrest due to VF. Cardiac optical mapping and electrophysiological mapping techniques have shown to be unvaluable resources to shape new hypotheses and develop novel mechanistic approaches and therapeutic strategies. This technology has allowed for many years testing new pharmacological or ablative therapeutic strategies, and developing multidomain methods to accurately track arrhymia dynamics identigying dominant sources and attractors. Even though, panoramic mapping is the primary method for simultaneously tracking electrophysiological parameters, its adoption by the multidisciplinary cardiovascular research community is limited mainly due to the cost of the technology. Taking advantage of recent technological advances, we focus on developing and validating low-cost optical mapping systems for panoramic imaging using clinically relevant models for basic research and bioengineering.Calvo Saiz, CJ. (2022). Novel Cardiac Mapping Approaches and Multimodal Techniques to Unravel Multidomain Dynamics of Complex Arrhythmias Towards a Framework for Translational Mechanistic-Based Therapeutic Strategies [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182329TESI

Neuroglia

This book is a compiled version of the journal Neuroglia. It was a peer-review Open Access journal by MDPI that investigated a wide range of glia related topics. Now the journal is published as a section of the journal Brain Sciences, with a new section Editor-in-Chief Prof. Sergey Kasparov