Minimizing Stimulus Current in a Wearable Pudendal Nerve Stimulator Using Computational Models.

After spinal cord injury, functions of the lower urinary tract may be disrupted. A wearable device with surface electrodes which can effectively control the bladder functions would be highly beneficial to the patients. A trans-rectal pudendal nerve stimulator may provide such a solution. However, the major limiting factor in such a stimulator is the high level of current it requires to recruit the nerve fibers. Also, the variability of the trajectory of the nerve in different individuals should be considered. Using computational models and an approximate trajectory of the nerve derived from an MRI study, it is demonstrated in this paper that it may be possible to considerably reduce the required current levels for trans-rectal stimulation of the pudendal nerve compared to the values previously reported in the literature. This was corroborated by considering an ensemble of possible and probable variations of the trajectory. The outcome of this study suggests that trans-rectal stimulation of the pudendal nerve is a plausible long term solution for treating lower urinary tract dysfunctions after spinal cord injury

Design of a wearable device for conditional neuromodulation of the pudendal nerve

After spinal cord injury, the normal functions of the lower urinary tract may be disrupted. Namely, incontinence and concurrent voiding problems may ensue. The troublesome side effects of the drugs, infection due to catheterisation, and the costs and risks associated with more invasive treatments indicate the need for alternative forms of treatment. The pudendal nerve neuromodulation may provide such an alternative. The unique aspect of this technique is that depending on the stimulus frequency it may result in micturition-like or continence-like reflexes. Also, the stimulus current can be applied trans-rectally, meaning that a minimally-invasive wearable solution may be developed. The major limitation of such a solution is the high level of the required stimulus current to activate the nerve trans-rectally. The efficacy of the trans-rectal neuromodulation of the pudendal may be increased by only applying the stimulus when needed, when employed to tackle incontinence. The electromyogram signal from the external anal sphincter may be used to detect the onset of hyper-reflexive contractions of the bladder. The ability of recording this signal can be readily incorporated in the neuromodulation device due to the proximity of the structures. However, the recording electrodes should be designed for an efficacious and chronic recording. Thus, the main objective of this thesis was to design and optimise the neuromodulation and recording electrodes on the said device. A volume conductor model of such a device in situ was developed and used in tandem with a double layer cable model of nerve fibres to minimise the stimulus current. It was demonstrated that a considerable reduction in the stimulus current may be achieved even when the variations of the nerve trajectory in different individuals are considered. Using computational models and experimental measurements, a recording assembly was identified for an efficacious recording of the electromyogram from the external anal sphincter

Bladder Volume Decoding from Afferent Neural Activity

RÉSUMÉ Lorsque les fonctions de stockage et de miction de la vessie échouent à la suite de traumatismes médullaires, ou en raison d'autres maladies neurologiques, de conditions de santé ou au vieillissement, des complications graves pour la santé du patient se produisent. Actuellement, il est possible de restaurer partiellement les fonctions de la vessie chez les patients réfractaires aux médicaments à l'aide des neurostimulateurs implantables. Pour améliorer l'efficacité et la sécurité de ces neuroprothèses, il faut un capteur de la vessie capable de détecter l’urine stockée afin de mettre en place un système en boucle fermée qui applique la stimulation électrique uniquement lorsque nécessaire. Le capteur peut également servir à aviser les patients ayant des sensations affaiblies pour les aviser en temps opportun le moment où la vessie doit être vidée ou quand un volume résiduel postmictionnel anormalement élevé reste après une miction incomplète. Dans cette thèse, on présente de nouvelles méthodes de mesure, ainsi qu’un processeur de signal numérique dédié pour décoder en temps réel le volume de la vessie à partir des enregistrements neuronaux afférents provenant des récepteurs naturels présents dans la paroi de la vessie. Nos principales contributions sont rapportées dans trois articles de journaux avec comité de lecture. On présente d'abord une revue exhaustive de la littérature comprenant des articles de journaux, des brevets et les livres les plus réputés portant sur l'anatomie, la physiologie et la physiopathologie du tractus urinaire inférieur ainsi que sur la mesure du volume ou la pression de la vessie. Cette étude nous a permis d'identifier les besoins qu'un capteur de la vessie doit satisfaire pour être utilisé dans des applications chroniques telles que celles proposées dans cette thèse. On présente aussi le résultat d’une analyse exhaustive des caractéristiques anatomiques et physiologiques de la vessie que nous avons identifiées d’avoir exercé une influence, ou même d’avoir empêché, la réalisation d'un tel capteur dans des études faites au cours des dernières années. Sur la base de cette étude et de l'évaluation systématique des méthodes de mesure pour la vessie, on a conclu que le principe de mesure le mieux adapté pour la surveillance chronique du volume de la vessie était la détection, la discrimination et le décodage de l'activité neuronale afférente découlant des récepteurs spécialisés du volume (mécanorécepteurs), au sujet desquels certains auteurs ont émis l'hypothèse de leur existence dans la muqueuse interne de la vessie. Ensuite, on présente la méthode de mesure qui permet d'estimer en temps réel le volume de la vessie à partir de l'activité afférente des mécanorécepteurs. Notre méthode a été validée avec les----------ABSTRACT Failure of the storage and voiding functions of the urinary bladder due to spinal cord injury (SCI), neural diseases, health conditions, or aging, causes serious complications in a patient's health. Currently, it is possible to partially restore bladder functions in drug-refractory patients using implantable neurostimulators. Improving the efficacy and safety of these neuroprostheses used for bladder functions restoration requires a bladder sensor (BS) capable of detecting urine volume in real-time to implement a closed-loop system that applies electrical stimulation only when required. The BS can also trigger an early warning to advise patients with impaired sensations when the bladder should be voided or when an abnormally high post-voiding residual volume remains after an incomplete voiding. In this thesis, we present new measurement methods and a dedicated digital signal processor for real-time decoding of the bladder volume through afferent neural signals arising from natural receptors present in the bladder wall. The main contributions of this thesis have been reported in three peer-reviewed journal papers. We first present a comprehensive literature review, including papers, patents and mainstay books of bladder anatomy, physiology, and pathophysiology. This review allowed us to identify the requirements (user needs) that a BS must meet for chronic applications, such as those proposed in this thesis. An exhaustive analysis of the particular anatomical and physiological characteristics of the bladder, which we realized had influenced or prevented the achievement of a BS for monitoring the bladder volume or pressure in past studies, are also presented. Based on this study and on a systematic assessment of the measurement methods published in past years, we determined the best measurement principle for chronic bladder volume monitoring: the detection, discrimination and decoding of the afferent neural activity stemming from specialized volume receptors (mechanoreceptors), on which some authors had hypothesized about its existence in the bladder inner mucosa. Next, we present methods that allows for a real-time estimation of bladder volume through the afferent activity of the bladder mechanoreceptors. Our method was validated with data acquired from anesthetized rats in acute experiments. It was possible to qualitatively estimate three states of bladder fullness in 100% of trials when the recorded afferent activity exhibited a Spearman’s correlation coefficient of 0.6 or better. Furthermore, we could quantitatively estimate the bladder volume, and also its pressure, using time-windows of properly chosen duration. The mea

Personalized medicine in surgical treatment combining tracking systems, augmented reality and 3D printing

Mención Internacional en el título de doctorIn the last twenty years, a new way of practicing medicine has been focusing on the problems and needs of each patient as an individual thanks to the significant advances in healthcare technology, the so-called personalized medicine. In surgical treatments, personalization has been possible thanks to key technologies adapted to the specific anatomy of each patient and the needs of the physicians. Tracking systems, augmented reality (AR), three-dimensional (3D) printing and artificial intelligence (AI) have previously supported this individualized medicine in many ways. However, their independent contributions show several limitations in terms of patient-to-image registration, lack of flexibility to adapt to the requirements of each case, large preoperative planning times, and navigation complexity. The main objective of this thesis is to increase patient personalization in surgical treatments by combining these technologies to bring surgical navigation to new complex cases by developing new patient registration methods, designing patient-specific tools, facilitating access to augmented reality by the medical community, and automating surgical workflows. In the first part of this dissertation, we present a novel framework for acral tumor resection combining intraoperative open-source navigation software, based on an optical tracking system, and desktop 3D printing. We used additive manufacturing to create a patient-specific mold that maintained the same position of the distal extremity during image-guided surgery as in the preoperative images. The feasibility of the proposed workflow was evaluated in two clinical cases (soft-tissue sarcomas in hand and foot). We achieved an overall accuracy of the system of 1.88 mm evaluated on the patient-specific 3D printed phantoms. Surgical navigation was feasible during both surgeries, allowing surgeons to verify the tumor resection margin. Then, we propose and augmented reality navigation system that uses 3D printed surgical guides with a tracking pattern enabling automatic patient-to-image registration in orthopedic oncology. This specific tool fits on the patient only in a pre-designed location, in this case bone tissue. This solution has been developed as a software application running on Microsoft HoloLens. The workflow was validated on a 3D printed phantom replicating the anatomy of a patient presenting an extraosseous Ewing’s sarcoma, and then tested during the actual surgical intervention. The results showed that the surgical guide with the reference marker can be placed precisely with an accuracy of 2 mm and a visualization error lower than 3 mm. The application allowed physicians to visualize the skin, bone, tumor and medical images overlaid on the phantom and patient. To enable the use of AR and 3D printing by inexperienced users without broad technical knowledge, we designed a step-by-step methodology. The proposed protocol describes how to develop an AR smartphone application that allows superimposing any patient-based 3D model onto a real-world environment using a 3D printed marker tracked by the smartphone camera. Our solution brings AR solutions closer to the final clinical user, combining free and open-source software with an open-access protocol. The proposed guide is already helping to accelerate the adoption of these technologies by medical professionals and researchers. In the next section of the thesis, we wanted to show the benefits of combining these technologies during different stages of the surgical workflow in orthopedic oncology. We designed a novel AR-based smartphone application that can display the patient’s anatomy and the tumor’s location. A 3D printed reference marker, designed to fit in a unique position of the affected bone tissue, enables automatic registration. The system has been evaluated in terms of visualization accuracy and usability during the whole surgical workflow on six realistic phantoms achieving a visualization error below 3 mm. The AR system was tested in two clinical cases during surgical planning, patient communication, and surgical intervention. These results and the positive feedback obtained from surgeons and patients suggest that the combination of AR and 3D printing can improve efficacy, accuracy, and patients’ experience In the final section, two surgical navigation systems have been developed and evaluated to guide electrode placement in sacral neurostimulation procedures based on optical tracking and augmented reality. Our results show that both systems could minimize patient discomfort and improve surgical outcomes by reducing needle insertion time and number of punctures. Additionally, we proposed a feasible clinical workflow for guiding SNS interventions with both navigation methodologies, including automatically creating sacral virtual 3D models for trajectory definition using artificial intelligence and intraoperative patient-to-image registration. To conclude, in this thesis we have demonstrated that the combination of technologies such as tracking systems, augmented reality, 3D printing, and artificial intelligence overcomes many current limitations in surgical treatments. Our results encourage the medical community to combine these technologies to improve surgical workflows and outcomes in more clinical scenarios.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidenta: María Jesús Ledesma Carbayo.- Secretaria: María Arrate Muñoz Barrutia.- Vocal: Csaba Pinte

Smart Biofeedback

Smart biofeedback is receiving attention because of the widespread availability of advanced technologies and smart devices that are used in effective collection, analysis, and feedback of physiologic data. Researchers and practitioners have been working on various aspects of smart biofeedback methodologies and applications by using wireless communications, the Internet of Things (IoT), wearables, biomedical sensors, artificial intelligence, big data analytics, clinical virtual reality, smartphones, and apps, among others. The current paradigm shift in information and communication technologies (ICT) has been propelling the rapid pace of innovation in smart biofeedback. This book addresses five important topics of the perspectives and applications in smart biofeedback: brain networks, neuromeditation, psychophysiological psychotherapy, physiotherapy, and privacy, security, and integrity of data

Brain Tumour Classification Using Deep Features from Structural MRI

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Recent Advances in Minimally Invasive Surgery

Minimally invasive surgery has become a common term in visceral as well as gynecologic surgery. It has almost evolved into its own surgical speciality over the past 20 years. Today, being firmly established in every subspeciality of visceral surgery, it is now no longer a distinct skillset, but a fixed part of the armamentarium of surgical options available. In every indication, the advantages of a minimally invasive approach include reduced intraoperative blood loss, less postoperative pain, and shorter rehabilitation times, as well as a marked reduction of overall and surgical postoperative morbidity. In the advent of modern oncologic treatment algorithms, these effects not only lower the immediate impact that an operation has on the patient, but also become important key steps in reducing the side-effects of surgery. Thus, they enable surgery to become a module in modern multi-disciplinary cancer treatment, which blends into multimodular treatment options at different times and prolongs and widens the possibilities available to cancer patients. In this quickly changing environment, the requirement to learn and refine not only open surgical but also different minimally invasive techniques on high levels deeply impact modern surgical training pathways. The use of modern elearning tools and new and praxis-based surgical training possibilities have been readily integrated into modern surgical education,which persists throughout the whole surgical career of modern gynecologic and visceral surgery specialists

Dementia in Parkinson’s Disease

An estimated 50% to 80% of individuals with Parkinson’s disease experience Parkinson’s disease dementia (PDD). Based on the prevalence and clinical complexity of PDD, this book provides an in-depth update on topics including epidemiology, diagnosis, and treatment. Chapters discuss non-medical therapies and examine views on end-of-life issues as well. This book is a must-read for anyone interested in PDD whether they are a patient, caregiver, or doctor