Les applications thérapeutiques de la neurostimulation ultrasonore représentent un terrain de recherche très prometteur, auquel il fait défaut un modèle valide décrivant les biomécanismes sous-jacents. Le premier objectif de ce travail de thèse était de proposer un modèle nerveux propice à une étude mécanistique du phénomène de neurostimulation ultrasonore. L’objectif suivant était de prouver l’intérêt d’exploiter ce modèle pour recueillir des informations concernant les interactions biophysiques ayant lieu entre les ultrasons (US) focalisés et le système nerveux. La majorité des études réalisées a porté sur le système nerveux du ver de terre commun, Lumbricus terrestris. Elles ont consisté d’une part à comparer entre elles les caractéristiques temporelles des réponses nerveuses associées à différentes modalités de stimulation, et d’autre part à évaluer l’influence de chacun des paramètres acoustiques du stimulus ultrasonore sur le taux de succès de neurostimulation (NSR). Dans les deux cas, la méthodologie suivie reposait sur l’administration de différents stimuli aléatoirement alternés. Complémentairement, le rôle joué par la cavitation acoustique a été étudié. La faisabilité de la stimulation du système nerveux du ver de terre, au moyen d’US et dans des conditions in vivo, a été prouvée. Les aires sensorielles et la dynamique de réponses associées aux trois modalités de stimulation ont été caractérisées. Il a été conclu que, dans ce modèle nerveux invertébré, pendant le phénomène de neurostimulation ultrasonore, les structures nerveuses interagissant fonctionnellement avec les US sont les nerfs afférents segmentaux. Les résultats des études paramétriques ont indiqué que le NSR augmente avec l’intensité acoustique, la durée de pulse et la fréquence de répétition des pulses. Il a été proposé que la structure nerveuse visée est sensible à la « force de radiation moyenne » transportée par le stimulus US, indépendamment des paramètres menant à cette valeur / Ultrasound neurostimulation applied to therapy is a promising field of research but still lacks of a validated model explaining the biomechanisms underlying the phenomenon. The first objective of this PhD thesis was to propose a nervous model suited for a mechanistic study of the phenomenon of ultrasound neurostimulation. In a second time, it was intended to practically prove the interest of this model by using it to gain knowledge regarding the biophysical interactions between focused ultrasound and the nervous system. Studies were performed on the nervous system of the anesthetized earthworm, Lumbricus terrestris. They consisted in either comparing the timings of the nervous responses associated with different modalities of stimulation, or evaluating the influence of each acoustic parameter on the neurostimulation success rate (NSR). In both cases, the methodology followed was to administer randomly mixed sequences of different stimuli. The feasibility of the in vivo activation of the anesthetized earthworm’s nervous system was proven. The sensory fields and response dynamics associated with the three modalities of stimulation were characterized. The parametric studies indicated that the NSR increases with pulse amplitude, pulse duration, pulse repetition frequency, but is more weakly influenced by the harmonic content and number of pulses. By applying a causal approach to interpret the results, we concluded that, in this nervous model, during the phenomenon of ultrasound neurostimulation, the structures functionally responding to the ultrasound stimulus are the segmental afferent nerves. We hypothesize that the main interaction with the axonal regions is mediated by ultrasound radiation force, without excluding the involvement of other biomechanisms

L'IRM est généralement considérée comme une méthode d'imagerie extrêmement sûre. Cependant, en présence d'implants conducteurs, des risques pour la santé du patient existent, plus particulièrement en terme d'échauffement radio-fréquence (RF) des tissus en contact avec l'implant. Suivant les recommandations des fabricants et des autorités sanitaires, certains dispositifs implantés sont autorisés en environnement IRM, sous conditions strictes qui limitent la qualité des images ou rendent l'acquisition impossible. Le but de cette thèse était d'optimiser et de valider les méthodes pour l'évaluation de la sécurité IRM en présence d'implants. Augmenter la prévisibilité des échauffements qui risquent de se produire dans chaque cas précis devrait permettre un élargissement des applications possibles de l'IRM chez des patients porteurs d'implants actifs.Ce projet est basé sur trois approches :- Des mesures et développements de méthodes IRM sur des objet-tests. Des techniques pré-existantes de cartographie du champ RF ont été optimisées afin de couvrir l'ensemble de la gamme dynamique présente dans le cas de courants RF induits dans des conducteurs. Pour ce faire, la technique AMFI (“Actual Multiple Flip-Angle Imaging”) a été développée. Un travail d'optimisation a également été mené sur la thermométrie IRM rapide via la méthode PRFS (“Proton Resonance Frequency Shift”).- Le développement de simulations numériques visant à étudier les interactions électromagnétiques entre les implants et le résonateur RF, ainsi que leurs répercussions thermiques. Un modèle de résonateur RF a été construit et validé à la fois théoriquement et expérimentalement. Le réglage du résonateur a donné lieu au développement d'une méthode numérique originale permettant de déterminer rapidement et précisément les valeurs des capacités. L'évaluation des courants RF induits dans des implants filaires conducteurs, via l'utilisation des cartes de champ RF, a également été développée. Cette méthode de mesure des courants RF induits ouvre la possibilité d'évaluer la sécurité au niveau individuel par une acquisition à faible débit d'absorption spécifique, avant toute autre acquisition IRM, dans le cas d'un possible futur protocole incluant des patients.- La construction d'un modèle numérique simplifié d'une électrode de stimulation cérébrale, via l'utilisation de la théorie des lignes de transmission. Ce modèle rend les simulations RF abordables, et présente les mêmes propriétés électriques que l'électrode réelle. L'échauffement RF en présence d'une électrode DBS a ainsi pu être évalué numériquement par l'intermédiaire de simulations recouvrant la taille du résonateur RF corps-entier.L'ensemble des outils développés au cours de cette thèse permet finalement une amélioration des méthodes disponibles afin d'évaluer la sécurité RF en présence d'implants conducteurs. / MRI is generally considered to be an exceptionally safe imaging method. However, in the presence of electrically conducting implants health risks exist, particularly in terms of RF heating of the tissues in contact with the implant. Some implants are cleared by the manufacturers or regulatory agencies for MR imaging of patients, but only under strictly limited conditions which often degrade image quality and exclude many configurations. The goal of this thesis project was to optimize and validate the methods for the assessment of MR safety in the presence of active implants. Increasing the predictability of the risk of RF heating in individual subjects should allow MRI to find wider applications in patients implanted with active devices.This project is based on three distinct approaches:- Measurements and MR method developments performed on test objects. Existing B1-mapping techniques were optimized for the specific needs of high dynamic range encountered in the presence of induced RF currents in conductors, leading to the “Actual Multiple Flip-Angle Imaging” technique. Further work has been performed on the optimization of rapid “Proton Resonance Frequency Shift” MR thermography.- The development of numerical simulations of the electromagnetic interactions between the RF resonator and implants as well as their thermal impact. A numerical RF resonator model was built and validated it using both theoretical and experimental studies. The optimization of the resonator has led to the development of an original method to rapidly and precisely adjust the individual capacitor values to obtain a given targeted current distribution. Separately, the measurement of RF currents induced in conductive wires, via B1 mapping, was developed. This method to measure RF currents in a specific configuration opens the possibility to evaluate RF safety in individual subjects using a low-SAR prescan prior to other acquisitions, for use in hypothetical future protocols on patients.- The construction of a simplified numerical model of deep brain stimulation electrodes, using transmission line theory. This model renders RF simulations tractable, while exhibiting the same electrical behavior as the real implant, allowing evaluation of RF heating in simulations covering the size of a whole-body MR resonator.The set of tools developed improve upon the currently available methods for the evaluation of RF safety in the presence of conductive implants.

Habilitacijos procedūrai teikiamoje mokslo darbų apžvalgoje apibendrinama minimaliai invazinės endokrininių liaukų chirurgijos patirtis Vilniaus universiteto Pilvo chirurgijos centre. Apžvelgtos minimaliai invazinės skydliaukės operacijos, išanalizuoti ir apibendrinti dviejų klinikinių studijų rezultatai. 2004-2006 m. atliktoje perspektyvioje atsitiktinių imčių studijoje ,,Endoskopinės adrenalektomijos dviejų metodų įvertinimas“ pateikti ir išanalizuoti 70 pacientų, operuotų dėl įvairios antinksčių patologijos dviem minimaliai invaziniais būdais (laparoskopiniu bei endoskopiniu retroperitoniniu), rezultatai. Išanalizuota operacijos trukmės priklausomybė nuo antinksčio naviko dydžio, paciento kūno masės, palyginta kraujo netektis operacijos metu, operacinių komplikacijų skaičius. Įvertinus visus duomenis, prieita išvados, kad abu operacijos būdai geri, tačiau laparoskopinės adrenalektomijos išmokstama greičiau. 2005-2007 m. atliktame darbe ,,Minimaliai invazinė fokusuota ir tradicinė paratiroidektomija, gydant pirminį hiperparatiroidizmą: perspektyvioji, atsitiktinių imčių studija“ pateikiami pirminiu hiperparatiroidizmu sergančių pacientų, operuotų dviem būdais, gydymo rezultatai. Atsitiktinių imčių būdu 47 pacientai suskirstyti į dvi grupes: operuotų minimaliai invaziniu būdu (24 pacientai) ir operuotų tradiciniu Kocherio būdu (23 pacientai). Išanalizuota prieskydinės liaukos adenomos instrumentinių tyrimų diagnostinė vertė, palyginta operacijos trukmė, komplikacijų... [toliau žr. visą tekstą] / The experience of minimally invasive endocrine surgery accumulated at Vilnius University Centre of Abdominal Surgery is presented in this review of scientific publications submitted for habilitation procedure. The material concerning minimally invasive thyroid gland operations is summarized and the results of two clinical trials are evaluated. The results of prospective randomized study “Evaluation of two methods endoscopic adrenalectomy” were presented and analyzed; this study included 70 patients who underwent surgery for various pathology of adrenal glands; one group of the patients underwent laparoscopic minimally invasive operation and another one – endoscopic retroperitoneal minimally invasive surgery. The relationship between the size of adrenal gland tumour, patients’ body weight and duration of operation was analyzed; blood loss and rate of operative complications were compared. The evaluation of all data showed that both methods of surgery were acceptable; however, laparoscopic adrenalectomy was more was easier to learn. Clinical study “Minimally invasive focused and traditional parathyroidectomy for treatment of primary hyperparathyroidism: a prospective randomized study” was performed during the period since 2005 till 2007; the results of treatment of patients by means of two methods of surgery were presented. The patients (n = 47) were randomized into two groups; one group included 24 patients who were operated on using minimally invasive technique and another... [to full text]

Thèse doctorat : Electronique : Villeurbanne, INSA : 2006. / Titre provenant de l'écran-titre. Bibliogr. p. 156-162.

Malgré un traitement pharmacologique et chirurgical adapté, les crises d'épilepsie persistent chez environ 20% des patients. La neurostimulation des circuits générateurs et/ou de contrôle des crises constitue actuellement la principale approche thérapeutique non lésionnelle innovante dans certaines formes d'épilepsies pharmaco-résistantes qui ne peuvent bénéficier d'une chirurgie résective curative. L'objectif de ce travail a été de développer un nouveau système de stimulation intracérébrale profonde qui soit efficace pour la suppression des crises sur le long terme sur un modèle d'épilepsie absence chez le rat. Trois points principaux ont été abordés : (i) la caractérisation de l'activité des ganglions de la base (GB) pendant les crises; (ii) le développement d'un système de stimulation asservie sur le principe de "détection/stimulation" des crises; (iii) la quantification des effets antiépileptiques à long terme de la stimulation asservie. Les résultats obtenus ont permis de confirmer l'existence d'une propagation rapide des décharges de pointes ondes (DPO) du cortex vers le thalamus et les GB, et d'un contrôle endogène des crises par la substance noire réticulée (SNr), cible utilisée pour la modulation des crises. Malgré une période réfractaire de 40 s au cours de laquelle la stimulation est inefficace, les effets antiépileptiques de la stimulation asservie de la SNr se sont avérés probants : taux élevé d'interruption des DPO par la stimulation (97%) accompagné d'une diminution de la survenue des DPO au cours du temps. Ces résultats constituent une preuve de concept de l'utilisation de la neurostimulation stimulation asservie dans le traitement de certaines formes d'épilepsie.

TDCS is a form of non-invasive neurostimulation that is comprised of injection of current via strategically placed scalp electrodes into targeted areas of the brain. TDCS has shown therapeutic benefit for numerous clinical applications. This technique has not however been widely adopted due to high variability of response to the stimulation. Current state of the art methods for optimizing tDCS are based on FEM models that generally model tissue as isotropic and homogeneous and do not take into account inter subject variability of head tissue electrical properties. We therefore develop an in-vivo method of measuring and analyzing bioimpedance spectroscopy measurements of the head to estimate change to tDCS dose in neural tissues for different subjects. Finite element simulations are implemented on a realistic MRI derived head model. 5\% random Gaussian noise is added. Experimental bioimpedance measurements are taken of the heads of 8 subjects. We simulate sensitivity distribution and impedance for a variety of 2 and 4 electrode configurations over a wide frequency range. We also extract Cole parameters and implement PCA on simulated and experimental impedance. We demonstrate that the Cole model of the head can be accurately approximated by the sum in series of Cole systems of each tissue. Comparison of Cole parameters from various simulated electrode configurations show statistical differences (paired t test $p<.05$). PCA shows that close to 100\% of the variance between two impedance spectra is described along a single principal component. Variation described by the second principal component increases as a function of increasing inter electrode gap which may be related to changes in dose. FEM and experimentally derived Cole parameters show different trends for various electrode configurations, good agreement is however shown for the PCA results. The outcome of this research may lead to a higher tDCS efficacy by improving standardization and control of stimulation by relation of dose and bioimpedance spectra characteristics.

Movement disorders are a group of syndromes that often arise due to neurological abnormalities. Approximately 40 million Americans are affected by some form of movement disorder, significantly impacting patients’ quality of life and their ability to live independently. Deep brain stimulation (DBS) is one treatment that has shown promising results in the past couple decades, however, the currently used open-loop system has several drawbacks. By implementing a closed-loop or adaptive DBS (aDBS) system, the need for expensive parameter reprogramming sessions would be reduced, side-effects may be relieved, and habituation could be avoided. Several biomarkers, for example signals or activity derived from electroencephalogram (EEG), could potentially be used as a feedback source for aDBS. Here, we attempted to characterize cortical EEG potentials in healthy subjects performing six tasks that are difficult for those with movement disorders. Using a 32-channel EEG cap with an amplifier sampling at 500 Hz, we performed our protocol on 11 college-aged volunteers lacking any known movement disorder. For each task, we analyzed task-related power (TRP) changes, spectrograms, and topographical maps. In a finger movement exercise, we found task-related depression (TRD) in the delta band at the F4 electrode, as well as TRD at the C3 electrode in the alpha band during a pencil-pickup task, and TRD at the F3 electrode in the beta band during voluntary swallowing. While delta-ERD in the finger movement exercise was likely due to ocular artifact, the other significant results were in line with what relevant literature would predict. The findings from the work, in conjunction with a future study involving movement disorder patients, can provide insight into the use of EEG as a feedback source for aDBS. Keywords: EEG, electroencephalography, neurostimulation, deep brain stimulation, movement disorders, closed-loop DBS, adaptive DBS, aDBS

This thesis explores potential use of GPGPU libraries to accelerate k-Wave toolkit's acoustic wave propagation simulation. Firstly, the thesis researches and assesses available high level GPGPU libraries. Afterwards, an insight into k-Wave toolkit's current state of simulation acceleration is provided. Based on that, an approach to enhance currently available code for processors into a heterogeneous application, that is capable of being run on graphics card, is proposed. The outcome of this thesis is an application that can utilize graphics card. If graphics card is unavailable, a fallback into thread and SIMD based acceleration for processor is executed. The product of this thesis is then evaluated based on its performance, maintenance difficulty and usability.

Since the 1900s, the number of deaths attributable to cardiovascular disease has steadily risen. With the advent of antihypertensive drugs and non-invasive surgical procedures, such as intravascular stenting, these numbers have begun to level off. Despite this trend, the number of patients diagnosed with some form of cardiovascular disease has only increased. By 2030, prevalence of coronary heart disease is expected to increase approximately by 18% in the United States. By 2050, prevalence of peripheral arterial occlusive disease is expected to increase approximately by 98% in the U.S. No single drug or surgical intervention offers a complete solution to these problems. Thus, a multi-faceted regimen of lifestyle changes, medication, and device or surgical interventions is usually necessary. A potential adjunct therapy and cost-effective solution for treating cardiovascular disease that has been overlooked is neurostimulation. Recent studies show that using neurostimulation techniques, such as transcutaneous electrical nerve stimulation (TENS), can help to reduce ischemic pain, lower blood pressure, increase blood flow to the periphery, and decrease systemic vascular resistance. The mechanisms by which these hemodynamic changes occur is still under investigation. The primary aim of this thesis is to elucidate these mechanisms through a thorough synthesis of the existing literature on this subject. Neurostimulation, specifically TENS, is thought to modulate both the metaboreflex and norepinephrine release from sympathetic nerve terminals. To test the hypothesis that TENS increases local blood flow, decreases mean arterial pressure, and decreases cutaneous vascular resistance compared to placebo, in which the electrodes are attached but no electrical stimulation is applied, a protocol was developed to test the effect of neurostimulation on healthy subjects. Implementation of this protocol in a pilot study will determine if neurostimulation causes significant changes in blood flow using the most relevant perfusion measurement instrumentation. Before conducting this study, pre-pilot comparison studies of interferential current therapy (IFC) versus TENS, low frequency (4 Hz) TENS versus high frequency (100 Hz) TENS, and electrode placement on the back versus the forearm were conducted. The only statistically significant difference found was that the application of IFC on the back decreased the reperfusion time, meaning that the time required to reach the average baseline perfusion unit value after occlusion decreased. Further pre-pilot work investigating these different modalities and parameters is necessary to ensure that favorable hemodynamic changes can be detected in the pilot study.

This thesis deals with the treatment of chronic pain by using neuromodulation, where a external generator is used in a trial period. In the first section the principle of pain management is described and then the main nature of neuromodulation. The possibilities of chronic pain suppression are described, where we are mainly dealing with neurostimulation (stimulation with electric current). For better understanding, examples of neurostimulation usage are shown, where and in what problems it is used. Because this work deals with an external generator for a trial period (a trial system), the possibilities of testing electric impulses are described, which are then used in a implantable generator IPG. The requirements for such a external generator are also described, which are important for the design of such a device. The design of the device is firstly modeled by a block scheme, where function of the separate blocks is described and afterwards, the entire design of the external generator for neuromodulation is given. The test sample of the external generator is manufactured and tested.