<div>Soft tissue manipulation is a widely used practice by manual therapists from a variety of healthcare disciplines to evaluate and treat neuromusculoskeletal impairments using mechanical stimulation either by hand massage or specially-designed tools. The practice of a specific approach of targeted pressure application using distinguished rigid mechanical tools to breakdown adhesions, scar tissues and improve range of motion for affected joints is called Instrument-Assisted Soft Tissue Manipulation (IASTM). The efficacy of IASTM has been demonstrated as a means to improve mobility of joints, reduce pain, enhance flexibility and restore function. However, unlike the techniques of ultrasound, traction, electrical stimulation, etc. the practice of IASTM doesn't involve any standard to objectively characterize massage with physical parameters. Thus, most IASTM treatments are subjective to practitioner or patient subjective feedback, which essentially addresses a need to quantify therapeutic massage or IASTM treatment with adequate treatment parameters to document, better analyze, compare and validate STM treatment as an established, state-of-the-art practice.</div><div><br></div><div>This thesis focuses on the development and implementation of Quantifiable Soft Tissue Manipulation (QSTM™) Technology by designing an ergonomic, portable and miniaturized wired localized pressure applicator medical device (Q1), for characterizing soft tissue manipulation. Dose-load response in terms of forces in Newtons; pitch angle of the device with respect to treatment plane; stroke frequency of massage measured within stipulated time of treatment; all in real-time has been captured to characterize a QSTM session. A QSTM PC software (Q-WARE©) featuring a Treatment Record System subjective to individual patients to save and retrieve treatment diagnostics and a real-time graphical visual monitoring system has been developed from scratch on WINDOWS platform to successfully implement the technology. This quantitative analysis of STM treatment without visual monitoring has demonstrated inter-reliability and intra-reliability inconsistencies by clinicians in STM force application. While improved consistency of treatment application has been found when using visual monitoring from the QSTM feedback system. This system has also discriminated variabilities in application of high, medium and low dose-loads and stroke frequency analysis during targeted treatment sessions.</div>

In recent years, development of various imaging, recording and stimulation tools are rapidly advancing our knowledge of the human anatomy and its underlying interconnections. As a truly non-invasive tool, Magnetic Resonance Imaging (MRI), is creating new opportunities to understand large scale biological processes with a fine detail. Furthermore, novel materials and microfabrication techniques are allowing researchers to develop tools that record bio-signal or modulate complex physiology with high temporal precision. However, these tools, when used individually can elucidate only a partial view of the human body and the brain. There is a growing need in both the research and clinical community to find ways to perform these modalities together and visualize biological systems across a vast range of spatiotemporal scale. However, severe methodological challenges act as bottlenecks for any such multimodal integration.<br><div><br></div><div>To address this critical need, I have designed an MRI-safe platform for high-fidelity bio-signal recording and electrical stimulation during concurrent MRI imaging. Central to this system are novel miniaturized microelectronic devices, that operate wirelessly in synchrony with MRI scans. The system leverages surplus functionalities of a conventional scanner to integrate with the imaging system and provide a simple and inexpensive solution towards multimodal imaging. This work also describes a systematic approach for development and evaluation of this plug-and-play system through in-vivo experiments in animal models. The clinical relevance of the multimodal imaging platform was further showcased through a study on the mechanism of SUDEP (Sudden death in epilepsy), a terminal complication associated with epilepsy. With future refinements, I expect this platform will provide affordable, accessible, and reliable solutions for multimodal imaging in animals and humans, creating unique opportunities for basic scientific research and clinical diagnosis.<br></div>

This thesis describes a novel method to reversibly and safely block nerve conduction using a low frequency alternating current (LFAC) waveform at 1 Hz applied through a bipolar extrafascicular electrode. This work follows up on observations made on excised mammalian peripheral nerves and earthworm nerve cords. An<i> in-situ</i> electrophysiology setup was used to assess the LFAC<br>waveform on propagating action potentials (APs) within the cervical vagus nerve in anaesthetized Sprague-Dawley rats (n = 12). Two sets of bipolar cuff or hook electrodes were applied unilaterally to the cervical vagus nerve, which was crushed rostral to the electrodes to exclude reflex effects<br>on the animal. Pulse stimulation was applied to the rostral electrode, while the LFAC conditioning waveform was applied to the caudal electrode. The efferent volley, if unblocked, elicits acute bradycardia and hypotension. The degree of block of the vagal stimulation induced bradycardia<br>was used as a biomarker. Block was assessed by the ability to reduce the bradycardic drive by monitoring the heart rate (HR) and blood pressure (BP) during LFAC alone, LFAC with vagal stimulation, and vagal stimulation alone. LFAC applied via a hook electrode (n = 7) achieved 86.6 +/- 11% block at current levels 95 +/- 38 uAp (current to peak). When applied via a cuff electrode (n = 5) 85.3 +/- 4.60% block was achieved using current levels of 110 +/- 65 uAp. Furthermore, LFAC was explored on larger vagal afferent fibers in larger human sized nerve bundles projecting to effects mediated by a reflex. The effectiveness of LFAC was assessed in an <i>in-situ</i> electrophysiological setup on the left cervical vagus in anaesthetized domestic swine (n = 5). Two bipolar cuff electrodes were applied unilaterally to the cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar extrafascicular cuff electrode was placed most rostral on the nerve for recording of propagating APs induced by<br>electrical stimulation and blocked via the LFAC waveform.<br>Standard pulse stimulation was applied to the left cervical vagus to induce the Hering-Breuer reflex. If unblocked, the activation of the Hering-Breuer reflex would cause breathing to slow down and potentially cease. Block was quantified by the ability to reduce the effect of the Hering-Breuer<br>reflex by monitoring the breathing rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone. LFAC achieved 87.2 +/- 8.8% (n = 5) block at current levels of 0.8 +/- 0.3 mAp. Compound nerve action potentials (CNAP) were monitored directly. They show changes<br>in nerve activity during LFAC, which manifests itself as the slowing and amplitude reduction of components of the CNAPs. Since the waveform is balanced, all forward reactions are reversed, leading to a blocking method that is similar in nature to DC block without the potential issues of<br>toxic byproduct production. These results suggest that LFAC can achieve a high degree of nerve block in both small and large nerve bundles, resulting in the change in behavior of a biomarker, <i>in-vivo </i>in the mammalian nervous system at low amplitudes of electrical stimulation that are within the water window of the electrode.<br>

<div>Energy-efficient communication has remained the primary bottleneck in achieving fully energy-autonomous IoT nodes. Several scenarios including In-Sensor-Analytics (ISA), Collaborative Intelligence (CI) and Context-Aware-Switching (CAS) of the cluster-head during CI have been explored to trade-off the energies required for communication and computation in a wireless sensor network deployed in a mesh for multi-sensor measurement. A real-time co-optimization algorithm was developed for minimizing the energy consumption in the network for maximizing the overall battery lifetime of individual nodes.</div><div><br></div><div>The difficulty of achieving the design goals of lifetime, information accuracy, transmission distance, and cost, using traditional battery powered devices has driven significant research in energy-harvested wireless sensor nodes. This challenge is further amplified by the inherent power intensive nature of long-range communication when sensor networks are required to span vast areas such as agricultural fields and remote terrain. Solar power is a common energy source is wireless sensor nodes, however, it is not reliable due to fluctuations in power stemming from the changing seasons and weather conditions. This paper tackles these issues by presenting a perpetually-powered, energy-harvesting sensor node which utilizes a minimally sized solar cell and is capable of long range communication by dynamically co-optimizing energy consumption and information transfer, termed as Energy-Information Dynamic Co-Optimization (EICO). This energy-information intelligence is achieved by adaptive duty cycling of information transfer based on the total amount of energy available from the harvester and charge storage element to optimize the energy consumption of the sensor node, while employing event driven communication to minimize loss of information. We show results of continuous monitoring across 1Km without replacing the battery and maintaining an information accuracy of at least 95%.</div><div><br></div><div>Decades of continuous scaling in semiconductor technology has resulted in a drastic reduction in the cost and size of unit computing. This has enabled the design and development of small form factor wearable devices which communicate with each other to form a network around the body, commonly known as the Wireless Body Area Network (WBAN). These devices have found significant application for medical purposes such as reading surface bio-potential signals for monitoring, diagnosis, and therapy. One such device for the management of oropharyngeal swallowing disorders is described in this thesis. Radio wave transmission over air is the commonly used method of communication among these devices, but in recent years Human Body Communication has shown great promise to replace wireless communication for information exchange in a WBAN. However, there are very few studies in literature, that systematically study the channel loss of capacitive HBC for <i>wearable devices</i> over a wide frequency range with different terminations at the receiver, partly due to the need for <i>miniaturized wearable devices</i> for an accurate study. This thesis also measures and explores the channel loss of capacitive HBC from 100KHz to 1GHz for both high-impedance and 50Ohm terminations using wearable, battery powered devices; which is mandatory for accurate measurement of the HBC channel-loss, due to ground coupling effects. The measured results provide a consistent wearable, wide-frequency HBC channel loss data and could serve as a backbone for the emerging field of HBC by aiding in the selection of an appropriate operation frequency and termination.</div><div><br></div><div>Lastly, the power and security benefits of human body communication is demonstrated by extending it to animals (animal body communication). A sub-inch^3, custom-designed sensor node is built using off the shelf components which is capable of sensing and transmitting biopotential signals, through the body of the rat at significantly lower powers compared to traditional wireless transmissions. In-vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation accuracy >99% when compared to traditional wireless communication modalities, with a 50x reduction in power consumption.</div>

[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. / [CAT] 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/10251/182329 / TESIS

<p>Future long-duration space missions will take humans farther from the support resources of Earth than ever before. These missions will require microgravity surgical technologies in the case of an emergency that necessitates medical intervention. This experiment integrated three different surgical technologies for testing in weightlessness on parabolic flights: a surgical containment dome, a multi-function surgical wand, and a microgravity blood-air separator. Two fluid loops were utilized: one in which the surgical wand, containment dome, and a wound model were used to provide a realistic mixture of blood simulant and air to the blood-air separator. The other fluid loop used prescribed mixture ratios of air and blood to test the performance of the separator under varying conditions. The results of this experiment showed that the multi-functional surgical tool and dome functioned as designed. In addition, each separator successfully separated the blood and air from the mixture, allowing for future blood transfusion. With this demonstration, each system used in this experiment qualifies as technology readiness level 6. Advancing the technology readiness level of these technologies further will require long duration zero-g testing on-orbit before inclusion in authentic space mission emergency surgical strategy. </p>

<p>There are no commercially available wearable shoe in-sole sensors that are capable of measuring and distinguishing between shear and compression forces. Companies have already developed shoe sensors that simply measure pressure and make general inferences on the collected data with elaborate software [2, 3, 4, 5]. Researchers have also attempted making sensors that are capable of measuring shear forces, but they are not well suited for biomedical applications [61, 62, 63, 64]. This work focuses on the development of a novel wearable sensor system that is capable of identifying and measuring shear and compression forces through the use of capacitive sensing. Custom hardware and software tools such as materials test systems and capacitive measurement systems were developed during this work. Numerous sensor prototypes were developed, characterized, and optimized during the scope of this project. Upon analysis of the data, the best capacitive measurement system developed in this work utilized the CAV444 IC chip, whereas the use of the Arduino-derived measurement system required data filtering using median and Butterworth zero phase low pass filters. The highest dielectric constant reported from optimization experiments yielded 9.7034 (+/- 0.0801 STD) through the use of 60.2% by weight calcium copper titanate and ReoFlex-60 silicone. The experiments suggest certain sensors developed in this work feasibly measure and distinguish between shear and compressional forces. Applications for such technology focus on improving quality of life in areas such as managing diabetic ulcer formation, preventing injuries, optimizing performance for athletes and military personnel, and augmenting the scope of motion capture in biomechanical studies.</p>

<p>The last two decades have shown a boom in the field of wearable sensing technology. Particularly in the consumer industry, growing trends towards personalized health have pushed new devices to report many vital signs, with a demand for high accuracy and reliability. The most common technique used to gather these vitals is photoplethysmography or PPG. PPG devices are ideal for wearable applications as they are simple, power-efficient, and can be implemented on almost any area of the body. Traditionally PPGs were utilized for capturing just heart rate, however, recent advancements in hardware and digital processing have led to other metrics including respiratory rate (RR) and peripheral oxygen saturation (SpO2), to be reported as well. Our research investigates the potential for wearable devices to be used for outpatient apnea monitoring, and particularly the ability to detect opioid misuse resulting in respiratory depression. Ultimately, the long-term goal of this work is to develop a wearable device that can be used in the rehabilitation process to ensure both accountability and safety of the wearer. This document details contributions towards this goal through the design, development, and evaluation of a device called “Kick Ring”. Primarily, we investigate the ability of Kick Ring to record heartrate (HR), RR, and SpO2. Moreover, we show that the device can calculate RR in real time and can provide an immediate indication of abnormal events such as respiratory depression. Finally, we explore a novel method for reporting apnea events through the use of several PPG characteristics. Kick Ring reliably gathers respiratory metrics and offers a combination of features that does not exist in the current wearables space. These advancements will help to move the field forward, and eventually aid in early detection of life-threatening events.</p>

<p>Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy that kills 1̃2 of every 10,000 epileptic patients every year. SUDEP has proven difficult to study because it frequently occurs unobserved and cannot be predicted. What limited clinical data exists suggests that SUDEP occurs as a cardiorespiratory collapse immediately following a seizure. In this work, I explore how a group of autonomic reflexes termed collectively as “oxygen‐conserving reflexes (OCRs)” lead to sudden death when activated during seizures. I also demonstrate multiple physiological parallels between the OCR‐mediated deaths that I report and the clinical data on cases of human SUDEP. Additionally, I explore the neural pathway underlying OCRs, identify the carotid body as a potential target for intervention, and demonstrate the efficacy of electroceutical intervention in reducing the mortality risk of OCR activation during seizures. This work seeks to both offer a neural explanation for SUDEP as well as present a promising target and means for potential intervention.</p>