Дисертації з теми "Deep Invasive Endometriosis (DIE)"

L’endométriose est une pathologie chronique qui provoque des douleurs pelviennes et une infertilité. On décrit trois phénotypes d’endométriose :l’endométriose péritonéale superficielle, les kystes ovariens d’endométriose (endométriomes) et l’endométriose profonde.L’examen standard pour le diagnostic de l’endométriose est, encore aujourd’hui, la laparoscopie. Nous avons étudié, de façon prospective, l’utilité d’un examen non invasif, la tomographie par émission de positrons (PET), chez les patientes avec suspicion d’endométriose. Nous n’avons pas mis en évidence d’hyperactivité métabolique sur les images de PET pré opératoires, après injection de déoxyglucose marqué au 18F (18FDG), des lésions d’endométriose ayant été confirmées par laparoscopie. Nous avons réalisé, dans un second temps, la même étude après injection d’un analogue de la somatostatine, le DOTATATE, marqué au 68Ga, qui montre une avidité pour les récepteurs à la somatostatine (SSTR) de type 2. Dans cette dernière étude, seules les lésions d’endométriose profonde se sont révélées hyperactives sur les images pré opératoires de PET. Nous avons ensuite réalisé une étude immunohistochimique rétrospective sur différents échantillons d’endométriose superficielle, d’endométriomes et d’endométriose profonde. Nos résultats ont confirmé l’expression de SSTR de type 1 et 5 par les cellules épithéliales des trois phénotypes d’endométriose. Par contre, seules les lésions d’endométriose profonde exprimaient les SSTR de type 2.Le traitement chirurgical des endométriomes et de l’endométriose superficielle est bien codifié. Par contre, la chirurgie de l’endométriose profonde reste au cœur des débats dans la littérature. Nous avons évalué notre aptitude à appliquer les techniques de chirurgie mini-invasive aux procédures complexes telles que la résection des nodules d’endométriose profonde du septum recto-vaginal (NEPSRV). Nous avons évalué la faisabilité de la laparoscopie avec assistance robotique pour une autre procédure complexe :la dissection des ganglions para-aortiques dans le cadre des cancers du col utérin localement avancés. Nous l’avons jugée faisable et sûre pour les patientes. En l’absence de bénéfice démontré de la laparoscopie avec assistance robotique sur la laparoscopie conventionnelle pour le traitement des NEPSRV, nous avons décidé d’évaluer une nouvelle stratégie opératoire mini-invasive de résection des NEPSRV. Nous avons réalisé une analyse des 10 premières patientes opérées selon cette stratégie et avons montré une amélioration significative des symptômes et de la qualité de vie des patientes. Nous avons également étudié la morbidité post opératoire. Nous avons finalement étudié l’apport de la laparoscopie guidée par la fluorescence au traitement des NEPSRV et observé des résultats prometteurs.A l’avenir, les lésions symptomatiques d’endométriose profonde exprimant les SSTR2 pourraient être sélectionnées à l’aide d’un PET au 68Ga-DOTATATE afin d’être traitées, dans le cadre d’essais cliniques, par des analogues de la somatostatine. Ces thérapies ciblées permettaient, dans ces cas, d’éviter la chirurgie. Notre stratégie opératoire mini-invasive pourraient dès lors être appliquée aux lésions n’exprimant pas les SSTR2.
Doctorat en Sciences médicales (Médecine)
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OBJECTIFS : Dans cette thèse nous avons décrit une nouvelle technique de prise en charge de l'endométriose profonde postérieure recto-sigmoïdienne par ultrasons focalisés de haute intensité échoguidés par voie transrectale (TR-USgHIFU), avant de rechercher les facteurs limitants de cette technique ainsi que les moyens d’améliorer sa faisabilité et son efficacité. METHODES : Nous avons tout d’abord conduit une étude clinique de phase I pour tester la faisabilité du traitement par TR-USgHIFU à l’aide de la sonde FocalOne®. Nous avons ensuite réalisé une étude sur pièces anatomiques visant à rechercher les facteurs limitants l’utilisation de la sonde FocaleOne® et à tester un autre prototype de sonde HIFU comme alternative à cette dernière. Nous avons également réalisé une étude clinique observationnelle pour mesurer l’atténuation acoustique des lésions d’endométriose recto-sigmoïdienne et de l’intestin normal. Nous avons enfin mis au point un modèle murin d’endométriose sous-cutané pour évaluer les effets anatomo-pathologiques des HIFU sur l’endométriose. RESULTATS : Nous avons inclus 23 patientes dans l’étude clinique de phase I entre juin 2015 et octobre 2019 dont 20 ont pu être traitées (faisabilité de 87%). Aucun effet indésirable grave n’a été rapporté. Nous n’avons pas observé pas de modification significative du volume des lésions à 6 mois, mais nous rapportons une amélioration significative des symptômes douloureux digestifs et gynécologiques ainsi qu’une amélioration de la qualité de vie des patientes. Les analyses sur pièces anatomiques et sur IRM démontrent le rôle du sacrum et de la charnière recto-sigmoïdienne dans les limitations mécaniques de la sonde FocalOne®. L’utilisation d’une sonde moins encombrante avec une focale plus courte semble être bénéfique pour augmenter la faisabilité du traitement. Notre étude sur 13 patientes traitées chirurgicalement d’un nodule du rectum ou du sigmoïde, a montré que l’atténuation à 3 MHz de l’endométriose digestive est de 50,2 Np/m. Cette valeur est significativement plus élevée que celle de l’intestin sain (32,8 ; p<0,001). Nous avons enfin montré que le modèle murin hétérologue sous-cutané « BALB/c-nude#Ishikawa » est fiable et performant pour l’étude des effets des HIFU sur l’endométriose profonde digestive, en raison notamment d’une atténuation acoustique remarquablement proche de celle de l’endométriose recto-sigmoïdienne. Grâce à ce modèle nous avons démontré que le traitement HIFU provoquait une nécrose de type « ischémique » au niveau de la cible. CONCLUSION : Le traitement par TR-USgHIFU dans l’endométriose recto-sigmoïdienne est faisable et sûr. Son efficacité morphologique reste à démontrer mais son efficacité clinique significative est prometteuse. Il pourrait s’agir d’une alternative minimalement invasive de choix pour remplacer le traitement chirurgical dans cette indication, en particulier pour les lésions les plus basses situées
OBJECTIVES: In this thesis we describe a new technique for the management of rectosigmoid endometriosis by transrectal ultrasound-guided high intensity focused ultrasound ultrasound (TR-USgHIFU). We also review several limiting factors of this technique before assessing several modifications to improve the feasibility and the efficacy of the procedure. METHODS: We first conducted a phase I clinical trial to test the feasibility of TR-USgHIFU treatment using the FocalOne® device. We then carried out a study on anatomical specimens to assess the limiting factors of the FocaleOne® probe and to test another HIFU probe, which has smaller transducer and which is mounted on a flexible endoscope. We also performed an observational clinical study to measure the acoustic attenuation of rectosigmoid endometriosis lesions and that of normal bowel. Finally, we have developed a murine model of subcutaneous endometriosis to assess the pathophysiological effects of HIFU on endometriosis. RESULTS: We included 23 patients in the phase I clinical trial between June 2015 and October 2019. Treatment was carried out in 20 of these patients (87% feasibility). No serious adverse events have been reported. We did not find a significant morphological effect at 6 months, but we report a significant improvement on digestive and gynecological symptoms as well as on patients’ quality of life. Studies on anatomical specimens and on MRI pictures demonstrated the role of the sacrum and the recto-sigmoid hinge in the mechanical limitations of the FocalOne® probe. The use of a smaller probe with a shorter focal could be interesting in order to increase the feasibility of the treatment. Our study on 13 patients treated surgically for rectum or sigmoid endometriosis nodule, showed that attenuation of digestive endometriosis at 3 MHz is 50.2 Np / m. This value was significantly higher than attenuation of the normal bowel (32.8; p <0.001). We finally showed that the heterologous subcutaneous murine model "BALB / c-nude # Ishikawa" was reliable and efficient to study the effects of HIFU on digestive endometriosis, as the acoustic attenuation of its nodules are remarkably close to that of endometriosis lesions. Thanks to this model, we reported that HIFU lesions are associated with a higher rate of ischemic and coagulation necrosis. CONCLUSIONS: Treatment with TR-USgHIFU in rectosigmoid endometriosis is feasible and safe. Its morphological efficacy remains to be demonstrated, but its significant clinical efficacy is promising. It could become be a minimally invasive alternative to replace surgical treatment in this indication, especially for rectal lesions

L’endométriose est définie comme la présence de tissu endométrial et de stroma en dehors de la cavité utérine. Ses localisations les plus fréquentes sont le péritoine pelvien et les ovaires. L’endométriose infiltrante est classiquement décrite comme la présence de tissu endométriotique plus de cinq millimètres sous le péritoine pelvien ou la séreuse d’un organe. Histologiquement il s’agit d’une lésion endométriotique mais qui contrairement aux lésions ovariennes ou péritonéales contient significativement plus de muscle lisse et de fibrose et est davantage associée à la douleur. Les lésions infiltrantes peuvent être responsables de dysménorrhée, dyspareunie profonde et douleurs pelviennes chroniques sévères ayant un charactère hyperalgique tel qu’on peut le retrouver dans les douleurs neuropathiques. Ces douleurs nécessitent souvent la prise de quantités importantes d’antalgiques et ont des répercussions importantes sur la vie professionnelle, quotidienne et sexuelle des femmes atteintes. L’endométriose infiltrante présente un rapport histologique étroit avec les structures nerveuses du rétropéritoine ou les nerfs des organes atteints. Dans sa localisation rectovaginale il existe une relation histologique étroite entre les lésions d’endométriose et les nerfs ainsi qu’une correlation entre l’intensité de la douleur et le nombre de structures nerveuses envahies par l’endometriose ou engaînées dans la fibrose. Ces lésions infiltrantes expriment le «nerve growth factor» (NGF), une neurotrophine qui joue un rôle clé dans la genèse de l’hyperalgie et de la douleur. Les structures nerveuses du rétropéritoine pelvien expriment quant à elles le récepteur spécifique pour la neurotrophine NGF. Le système «NGF-récepteur spécifique» peut être responsable d’un chimiotactisme tissulaire entre les tissus sécrétant du NGF et les nerfs qui expriment le récepteur pour le NGF. Le système «NGF- récepteur spécifique» au sein de la relation endométriose-nerfs pourrait rendre compte du caractère hyperalgique des lésions endométriotiques infiltrantes ainsi, qu’expliquer pourquoi les lésions nodulaires n’apparaissent que dans les sites anatomiques richement innervés (ligaments utérosacrés, lame rectovaginale, paroi du rectum ou du côlon…) et pas ailleurs. Le traitement de première intention est chirurgical. Il convient d’être suffisamment agressif sur les lésions tout en engendrant le moins de séquelles postopératoires possibles sachant que nombre de ces femmes sont stériles. En cas d’atteinte digestive basse, les modalités de l’intervention sont dictées par l’extension et le degré d’infiltration de la paroi digestive. Dans le but de réaliser dans la majorité des cas une chirurgie minimalement invasive (laparoscopique) avec des cicatrices de petites tailles, nous avons développé une stratégie de traitement basée sur le degré d’infiltration de la paroi digestive. Dans ce cadre nous avons développé une technique laparo-assistée de résection colique segmentaire et de résection antérieure du rectum.
Doctorat en sciences médicales
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Deep brain stimulation (DBS) has emerged as an effective treatment for therapy resistant psychiatric and neurological disorders, such as dystonia. For subforms, so called task specific dystonia, interventions utilizing the effects of shift of locus of attention have been used. The mechanism of the latter nor of DBS are well understood. My work in the context of this thesis involved various methods including the use of combined DBS and functional Magnetic Resonance Imaging and cohorts with neuropsychiatric patients. However, this write-up summarizes four conceptually linked projects that explore the mechanistic relevance of cortical circuits for the aforementioned interventions. First, using electrophysiological methods, I explored the mechanisms of DBS during the early treatment phase in dystonia. Typically the time course is gradual, despite the fact that DBS instantly interacts with abnormal oscillations. The results led to the hypothesis that pre-existing high levels of plasticity had formed motor memories of dystonic movement patterns, and that even though synaptic plasticity was reduced quickly by DBS, it took time for the motor system to acquire more normal movement. Second, in long term DBS treated patients intriguingly it has been found that, in some cases (but not all), DBS can be stopped for many days without any return of symptoms. My research suggested that DBS leads to persisting functional changes in the brain and that different electrophysiological signatures are associated with the retention or the loss of achieved clinical benefit when DBS is stopped and that via the programming of DBS these can be shaped. In a subsequent study results suggested that the achieved clinical benefit might be at risk when DBS is interrupted for too long. Finally, non-invasive interventions using attention modulation unexpectedly shift cortical circuit excitation towards increased excitability irrespective of the locus of attention. This finding has several clinical implications.

Endometriosis is associated with locally dysregulated immune responses and increased lymphangiogenesis. This study aimed to examine endometrial-like cells and immune cell populations in uterine-draining iliac lymph nodes throughout the menstrual cycle and lymph nodes associated with deep infiltrating endometriotic lesions of the bowel. Paraffin-embedded uterine-draining iliac lymph nodes (endometriosis = 6, control = 9) and deep infiltrating bowel endometriotic lesion-associated nodes (n = 12) were immunohistochemically stained for endometrial-like cells and a range of immune cells. In uterine-draining iliac nodes, DC-Sign+ cell numbers and CD4 antigen expression peaked during menstruation, and CD20 antigen expression significantly decreased between the proliferative and secretory phases. In deep infiltrating bowel endometriosis associated nodes, CD10+ endometrial-like cells were decreased compared to iliac nodes; CD4+ numbers, and CD4 and FoxP3 antigen expression were increased but DC-Lamp+, CD20+ and CD57+ numbers and DC-Lamp, CD79 and CD57 antigen expression were decreased. The presence of endometrial-like cells and dysregulated immune cell environment in pelvic lymph nodes indicate an important role for the lymphatic system in endometriosis. This study provides new evidence for lymphatic and immune system involvement in the development and progression of endometriosis, which may open up new venues for exploring lymphatic-based therapeutic approaches.

L’endométriose est une maladie gynécologique pour laquelle l’exposition à certains contaminants chimiques environnementaux est évoquée parmi les facteurs de risque associés. Les conclusions des études épidémiologiques existantes restent toutefois non convergentes. Leur hétérogénéité en termes de lésions décrites, de méthodologie et d’effectifs contribuent à ce constat, de même que l’étendue limitée des marqueurs d’exposition considérés dans ces études. Nous avons réalisé une étude cas-témoins appariés à partir d’une bio-collection de 113 patientes réunissant68 cas de patientes opérées d’endométriose profonde et 45 patientes témoins. Un ensemble unique de 78 polluants organiques persistants a été recherché, incluant dioxines, polychlorobiphényles, retardateurs de flamme polybromés, et pesticides organochlorés. Les niveaux d’exposition interne des sujets ont été mesurés à la fois dans les tissus adipeux pariétal et épiploïque ainsi que dans le sérum. La distribution de ces différents polluants au sein de ces trois compartiments a tout d’abord été caractérisée. Celle-ci a permis la prise en compte encore très rare de l’équilibre entre compartiments de stockage et compartiment circulant, ce rapport de concentration apparaissant comme un potentiel indicateur additionnel permettant d’affiner d’éventuels liens de causalité entre exposition chronique à des dangers chimiques et pathologie chez l’homme. Certains des contaminants ciblés sont ensuite apparus significativement associés à l’endométriose profonde, la stratification plus fine de notre population de cas indiquant un lien d’autant plus significatif en présence d’endométriome. Les mécanismes sous-jacents de cette association restent toutefois à élucider
Endometriosis is a gynecological disease for whichexposure to some environmental chemicals is evocatedamong the associated risk factors. Epidemiological studies are however globally non convergent and finally fairly conclusive. Their heterogeneity in terms of lesion localization and sub-phenotype, methodology, size and nature of the populations studied, as well as the limited number of monitored markers of exposure contribute to this situation. We realized a matched case-control study based on a biocollection of 113 patients including 68 patients suffering of deep endometriosis and 45 controls. We characterized the internal exposure levels of an extended range of around 78 persistent organic pollutants (including dioxins, polychlorobiphenyls, brominated flame retardants and organochlorine pesticides). Internal level exposures were measured in three biological compartments (omental fat, subcutaneous fat and serum). First, the distribution of these chemicals was characterized within these compartments. These extended exposure data from deep infiltrating endometriosis patients are the first ones available for France and give a new insight about the equilibrium of chemicals between storage and circulating compartments that should be further considered as a potential indicator permitting to establish a possible association between a chronic exposure to chemical hazards and human pathology. Afterwards, some of the targeted chemicals appeared significantly associated with deep endometriosis. A sub-stratification of our case population indicated a more significant relationship with the presence of endometrioma. Underlying mechanisms remain to be determined

Endometriose (EM) ist eine häufige gynäkologische Erkrankung, die bei betroffenen Frauen unter anderem mit chronischen Unterleibsschmerzen und Unfruchtbarkeit einhergeht (VALLE 2002). Bisher war es bei den zur Forschung verwendeten Modelltieren für EM (z.B. Rhesusaffe, ZONDERVAN et al. 2004; Weißbüschelaffe, EINSPANIER et al. 2006) nicht möglich festzustellen, ob bei ihnen schmerzhafte Beeinträchtigungen durch die Erkrankung bestehen. Um die Auswirkungen neuer Therapeutika auf das Wohlbefinden der Patientinnen bewerten zu können, werden Methoden benötigt, mit denen EM bedingte Beeinträchtigungen der Modelltiere dargestellt werden können. Daher war es das Ziel dieser Studie, bei einem Primatenmodell für EM, dem Weißbüschelaffen, neue nicht invasive Testsysteme zu etablieren, die zur Darstellung von EM bedingten Schmerzen und Beeinträchtigungen geeignet sind. Unter der Annahme, dass schmerzhafte Erkrankungen das Verhalten (WALLACE et al. 1990), die Beweglichkeit (FLECKNELL 1986) sowie die kognitiven Fähigkeiten (SMITH et al. 2006) der betroffenen Tiere beeinträchtigen können, wurden drei nicht invasive Testsysteme auf ihre Eignung untersucht, Schmerzen bei an EM erkrankten Weißbüschelaffen im Vergleich zu Kontrolltieren darzustellen. Zur Untersuchung des Verhaltens wurde die Videoüberwachung, für die motorischen Fähigkeiten der Futterbaum (modifiziert nach ROBERTS et al. 1993) und für die kognitiven Fähigkeiten der Wisconsin General Test Apparatus (WGTA, HARLOW 1949) sowie der Futterbaum verwendet. Im ersten Abschnitt dieser Studie wurde das Normalverhalten von neun Weißbüschelaffenpaaren per Videokamera über den gesamten Tagesverlauf von zwölf Stunden aufgezeichnet und unter anderem in Bezug auf Aktivität, soziale und eigene Körperpflege sowie Futter- und Wasseraufnahme analysiert. Der Verlauf der Tagesaktivität zeigte drei Maxima zwischen 7:00 und 8:00 Uhr, 11:00 und 12:00 Uhr sowie 14:00 und 15:00 Uhr, dabei war die ansteigende Aktivität als Futtersuchverhalten vor den Mahlzeiten zu werten. Das im ersten Abschnitt der Studie dargestellte Aktivitätsmuster wurde im zweiten Abschnitt verwendet, um die Versuche mit WGTA und Futterbaum besser in den Tagesverlauf der Tiere einzuordnen und darüber ihre Kooperativität zu steigern. Die Tiere führten die Tests immer zur gleichen Tageszeit durch, deshalb wurde somit eine optimale Vergleichbarkeit und Homogenität der Ergebnisse gewährleistet. Bei der Auswertung der Videodokumentation im zweiten Abschnitt dieser Studie zeigte sich, dass erkrankte Weibchen ihren Partner im Gegensatz zu den Kontrolltieren gar nicht pflegen (p=0,029) und die Aktivität der erkrankten Weibchen zwar deutlich, aber nicht signifikant (p=0,057) verringert war. Diese verringerte Aktivität ist möglicherweise ein Hinweis auf Schmerzen der an EM erkrankten Weibchen, während die nicht vorhandene soziale Körperpflege den partnerschaftlichen Problemen betroffener Frauen entsprechen könnte. In den ersten beiden kognitiven Tests mit dem WGTA führten die erkrankten Weibchen signifikant weniger Versuche pro Tag durch als die Kontrolltiere (p=0,006/ p=0,008). Darüber hinaus benötigten die erkrankten Tiere signifikant mehr Versuche, um den ersten Test zu verstehen (p=0,008). Diese Unterschiede zu den Kontrolltieren ließen sich in den folgenden drei Versuchsabschnitten nicht mehr nachweisen. Daraus lässt sich ableiten, dass die Weibchen mit EM sich schlecht auf neue Anforderungen einstellen und sich weniger lange auf eine gestellte Aufgabe konzentrieren können. Nach der International Primatological Society (MC CANN et al. 2007) kann eine verminderte Fähigkeit, sich auf neue Situationen einzustellen, als Anzeichen für Beeinträchtigungen gewertet werden. Bei der Auswertung der Futterbaum Testreihen, in denen sowohl kognitive als auch motorische Fähigkeiten der Tiere mit einer Art „Kletterbaum“ überprüft wurden, ergaben sich demgegenüber keine signifikanten Unterschiede zwischen der EM-Gruppe und den Kontrolltieren. Zusammenfassend eignen sich die Videodokumentation und der WGTA zur Darstellung von Beeinträchtigungen bei an EM erkrankten Weißbüschelaffen. Die beiden Testsysteme können in folgenden pharmakologischen Studien verwendet werden, um erstmals die Auswirkungen neuer Therapeutika auf das Wohlbefinden der Modelltiere zu bewerten. Zusätzlich ermöglichen die Ergebnisse dieser Studie ein Refinement (RUSSELL und BURCH 1959), da die bisher verwendeten invasiven Methoden (Laparoskopie, Laparotomie) zur Bewertung des Verhaltens der EM Läsionen unter einer Therapie ergänzt und sogar ersetzt werden könnten
Endometriosis (EM) is a common gynecological disease, which is known to cause chronic pelvic pain and infertility in women (VALLE 2002). Up to now, it was not possible to assess, whether the animal models for research (e.g. rhesus macaque, ZONDERVAN et al. 2004; common marmoset, EINSPANIER et al. 2006) suffer from pain or impairments due to the disease. Therefore, new test systems are needed to obtain pain and discomfort in animal models for EM to enable the validation of new therapeutic agents with a view to the patients well being. It was the aim of this study, to establish new non invasive test systems to investigate signs of discomfort in an animal model for EM, the marmoset monkey. Assuming that painful diseases can influence the behaviour (WALLACE et al. 1990), the mobility (FLECKNELL 1986) and the cognitive abilities (SMITH et al. 2006) of animals, three non invasive test systems were reviewed for their ability to detect EM associated pain in common marmosets. They were based on behaviour (videotaping), mobility and exploratory behaviour (food tree, modified after ROBERTS et al. 1993) and cognitive abilities (Wisconsin General Test Apparatus (HARLOW 1949) and food tree). In the first part of this study, the daily activity patterns, allo- and autogrooming as well as water and food intake of nine common marmoset couples were monitored over a 12-hour light phase by video recording. The animals showed a trimodal course of activity per day with maxima from 7:00-8:00h, 11:00-12:00h and 15:00-16:00h. These activity maxima represented foraging behaviour, as they were followed by frequent food intake phases. The knowledge of the daily activity patterns allowed to optimize the experimental conditions for the tasks with the food tree and the Wisconsin General Test Apparatus (WGTA; HARLOW 1949) in the second part of this study. As every animal solved the tasks at the same time of day, the comparability and homogeneity of the results were optimized. By analysing the video documentation in the second part of this study, the females with EM, in contrast to the control females, did not show any social grooming behaviour (p=0.029). Furthermore, their activity level was almost significantly decreased (p=0.057). This reduced activity could indicate towards pain in the diseased females, while the lack of social grooming is similar to partnership problems in diseased women. The WGTA tasks revealed, that the females with EM performed significantly less trials per day in the first two settings (p=0.006/ p=0.008) and needed more trials to solve the first setting than the control animals (p=0.008). Those differences between diseased females and control animals were not detectable in the following three settings of the WGTA tasks. These results demonstrate, that EM affected marmosets have difficulties to concentrate on cognitive tasks and to cope with new situations. According to the International Primatological Society (MC CANN et al. 2007), these difficulties to cope with new situations can be interpreted as signs of distress. The food tree, a kind of jungle gym, was used to assess the animals` cognitive abilities as well as their mobility, but there were no significant differences between the EM diseased females and the control animals. In conclusion, the videotaping and the WGTA are suitable methods to demonstrate signs for impairments due to EM in marmoset monkeys. In following pharmacological studies, both test systems will allow to evaluate the benefit of new therapeutic agents on the animal model`s well being. In addition, the results of this study can help to refine procedures by replacing invasive methods like laparotomy according to the Refinement of RUSSELL and BURCH (1959)

Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, February 1999.
Includes bibliographical references (leaves 229-239).
by Douglas R. Daum.
Ph.D.

Includes bibliographical references
Motivation: Conventional surface electromyography (EMG) methods cannot be used to detect deep muscle activation. A new non-invasive superficial and deep muscle EMG (sdEMG) technique has recently been used to derive the EMG activity of Brachialis and Tibialis Posterior muscles in the upper and lower limb respectively. The aim of the present study was to apply a modified version of sdEMG to the forearm to detect EMG activity of the deep extrinsic thumb muscles Flexor Pollicis Longus (FPL), Extensor Pollicis Longus (EPL), Extensor Pollicis Brevis (EPB) and Abductor Pollicis Longus (APL) using surface electrodes. Methods: High density monopolar EMG was detected from 2 concentric rings, each consisting of 20 custom designed and manufactured silver electrodes, placed at the distal and proximal thirds of the right forearm of 15 healthy male participants. The EMG signals were recorded by a custom synthesised from open source components, EMG amplifier system interfacing with a custom designed LabVIEW® program. The participants performed 10 repetitions of isometric thumb flexion (TFl), thumb extension (TEx), thumb abduction (TAb), thumb adduction (TAd), index finger flexion (IFFl) and index finger extension (IFEx). Each isometric contraction was performed in a randomized order at a standardized effort level of 30% of the participant's maximum voluntary contraction (verified by a custom designed and built thumb dynamometer). The Independent Component Analysis (ICA) algorithm, fastICA, was used to un-mix the 40 monopolar EMG waveforms (containing EMG activity attributable to both superficial and deep muscles) into 40 constitutive components, known as the Independent Components (ICs). The activation envelope of the ICs was found using a 250ms RMS smoothing filter and normalized between 0 and 1. A contraction sequence specific predicted EMG waveform based on intramuscular measurements (from existing studies in the literature) was created for each deep muscle and correlated with the processed ICs using Pearson's Correlation Coefficient (r). The ICs were ranked according to the corresponding r value and the highest r ranked IC for each muscle was considered to represent the recovered EMG activity from that particular muscle. Finally, a per sample basis accuracy, sensitivity and specificity analysis was conducted between each deep muscle's predicted EMG and highest r ranked IC at different activation thresholds. A linear mixed-effects statistical model was used to find the overall accuracy, sensitivity and specificity values over all the thresholds for each deep muscle. Results: Overall correlations of 0.81 for FPL (D), 0.88 for EPL (D), 0.92 for EPB (D) and 0.83 for APL (D) (p<0.001 for all muscles) were found between the predicted EMG waveforms and ICs. Using an activation threshold of 3 standard deviations above a resting baseline level, statistically significant (p<0.001) accuracy, sensitivity and specificity measures were found between the predicted EMG waveforms and top r ranked ICs for each of the deep muscles. The values of the 3 statistical measures (accuracy, sensitivity, specificity) for each of the deep muscles were: FPL (0.76, 0.88, 0.70); EPL (0.87, 0.85, 0.91); EPB (0.94, 0.93, 0.94); APL (0.80, 0.87, 0.87). Conclusions: The results indicate that this is the first non-invasive detection of the EMG activity of FPL (D), EPL (D), EPB (D) and APL (D). The ability to detect movement intention as a result of activation from these muscles may be of use for robot based targeted rehabilitation of the hand or in the control of prosthetic hand devices.

The non-invasive and, often, continuous measurement of the hemodynamics of the body, and for the main purposes of this thesis, the brain, is desired because both the instantaneous values and their changes over time constantly adapt to the conditions affecting the body and its environment. They are altered in pathological situations and in response to increased function. It is desirable for these measurements to be continuous, reliable, minimally invasive, and relatively inexpensive. In recent years, optical techniques that, by using diffusing and deep-reaching (up to few centimeters) light at skin-safe levels of intensity, combine the aforementioned characteristics, have increasingly become used in clinical and research settings. However, to date there is, on one side the need to expand the number and scope of translational studies, and, on the other, to address shortcomings like the contamination of signals from unwanted tissue volumes (partial volume effects). A further important goal is to increase the depth of penetration of light without affecting the non-invasive nature of diffuse optics. My PhD was aimed at several aspects of this problem; (i) the development of new, more advanced methods, i.e. the time/pathlength resolved, to improve the differentiation between superficial and deeper tissues layers, (ii) the exploration of new application areas, i.e. to characterize the microvascular status of bones, to study the functional response of the baby brain, and (iii) to improve the quality control of the systems , i.e. by introducing a long shelf-life dynamic phantom. In conceptual order, first I introduce long shelf-life reference standards for diffuse correlation spectroscopy. Secondly, I describe the use of an existing hybrid time domain and diffuse correlation spectroscopy system to monitor the changes that some pathological conditions, in this case osteoporosis and human immunodeficiency virus infection, may have on many aspects of the human bone tissue that are currently not easy to measure (i.e. invasively assessed) by conventional techniques. Thirdly, I describe the development of a novel time domain optical technique that intimately combines, introducing many previously unmet advancements, the two previously cited optical spectroscopy techniques. For the first time I was able to produce a time domain device and protocol that can monitor the blood flow in vivo in the head and muscles of healthy humans. Lastly, I describe a device and method that I have used to monitor changes in blood flow in healthy human infants of three to five months of age, for the first time in this age bracket, as a marker of activation following visual stimulation. Overall, this work pushes the limit of the technology that makes use of diffuse light to minimally invasively, continuously, and reliably monitor endogenous markers of pathological and physiological processes in the human body.
La medición no invasiva y, a menudo, continua de la hemodinámica del cuerpo, y para los propósitos principales de esta tesis, del cerebro, es conveniente porque tanto los valores instantáneos como sus variaciones en el tiempo se adaptan constantemente a las condiciones que afectan el cuerpo humano y su entorno. Estas suelen alterarse en situaciones patológicas o como respuesta a una mayor función. Es deseable que estas mediciones sean continuas, confiables, mínimamente invasivas y relativamente asequibles. En los últimos años, las técnicas ópticas que, mediante el uso de luz difusa para medir los tejidos en profundidad (hasta unos pocos centímetros) mediante niveles de intensidad que son seguros para la piel, combinan las características arriba mencionadas, se han utilizado cada vez más tanto en entornos clínicos como de investigación. Sin embargo, al día de hoy hay, por un lado, la necesidad de ampliar el número y el ámbito de los estudios translacionales y, por el otro, de suplir a las deficiencias como por ejemplo la contaminación de volúmenes de tejido no deseados (efectos de volumen parcial). Otro objetivo importante es aumentar la profundidad de penetración de la luz sin afectar la naturaleza no invasiva de la óptica difusa. Mi doctorado está destinado a mejorar varios aspectos de este problema; (i) el desarrollo de nuevos métodos más avanzados, es decir, el método resuelto en el tiempo/trayectoria de los fotones, para mejorar la diferenciación entre los tejidos superficiales y profundos, (ii) la exploración de nuevas áreas de aplicación, es decir, para caracterizar el estado microvascular de los huesos, para estudiar la respuesta funcional del cerebro en los niños, y (iii) para mejorar el control de calidad de los sistemas, es decir, mediante la introducción de un phantom dinámico de larga vida útil. En orden conceptual, primero voy a introducir estándares de referencia de larga vida útil para la espectroscopia de correlación difusa (DCS). En segundo lugar, voy a describir el uso de un sistema híbrido espectroscopia tiempo-resuelta (TRS) con DCS ya existente para monitorizar los cambios que algunas condiciones patológicas, en este caso la osteoporosis y la infección por el virus de la inmunodeficiencia humana, pueden comportar para muchos aspectos del tejido óseo humano que actualmente no se pueden medir con facilidad (es decir, se van evaluado de forma invasiva) mediante técnicas convencionales. En tercer lugar, voy a describir el desarrollo de una novedosa técnica óptica en el dominio temporal que combina íntimamente, introduciendo muchos avances previamente no cumplidos, TRS y DCS. Por primera vez pude producir un dispositivo y un protocolo tiempo-resueltos para medir el flujo de la sangre en la cabeza y en los músculos de seres humanos sanos. Por último, en esta tesis voy a describir un dispositivo y un método que he usado para monitorear los cambios en el flujo sanguíneo como marcadores de activación del cerebro debida a estímulos visivos en bebés entre tres y cinco meses de edad. En general, este trabajo amplia los limites de la tecnología que hace uso de la luz difusa para monitorizar, de forma mínimamente invasiva, continua y confiable los marcadores endógenos de procesos patológicos y fisiológicos en el cuerpo humano.

The present study investigated a novel non-invasive superficial and deep surface electromyography (sdEMG) technique to detect and isolate extrinsic muscles of the hand with the aim of developing experimental guidelines to aid future studies. The sdEMG technique comprises of two or more surface electrode arrays encircling the limb under investigation set up in a monopolar EMG recording modality and a blind source separation (BSS) algorithm to decompose the recorded mixed monopolar EMG signals into their constituent components, which is proposed to reflect the underlying EMG activity of each muscle. Three experimental parameters linked to the finger movement protocol (MP) were investigated that varied the effects of timing, randomisation and movement anticipation on the ability of the sdEMG technique to detect and isolate the superficial muscles flexor digitorum superficialis (FDS) and extensor digitorum (ED), and the deep muscles extensor indicis (EI), extensor pollicis longus (EPL), flexor digitorum profundus (FDP) and flexor pollicis longus (FPL). FDS and FDP were split into FDS-Index, FDS-Ring, FDP-Index and FDP-Ring bands resulting in a total of eight muscles investigated. A standard movement protocol consisting of 12 dynamic movements was designed to target the activation of the investigated muscles during each experimental run. The Timing experiments varied the movement window duration to 3, 5 and 7 seconds using the standard MP sequence. The Randomisation experiment consisted of a randomised MP sequence. The Anticipation experiment presented participants with the current, and next movement instruction in the standard MP sequence. The developed sdEMG system implemented 64 custom-made surface electrodes arranged in three bands positioned around the distal third of the forearm. An OT Bioelettronica® EMG-USB2 256-channel biopotential amplifier was used, set up in a referenced monopolar EMG configuration. Contraction detection apparatus was built consisting of finger exoskeletons and flex sensors to record when finger movements occurred. A forearm testing platform was built to secure the participant’s forearm during experimental testing and a visual participant instruction system was developed to convey the timed movement instructions. Five healthy, right-hand dominant male participants (mean ± SD; age: 24 ± 3 years) without any history of neuromuscular diseases or disabilities were recruited for the study. Each participant completed five experimental runs of the five MP variations while the EMG and flex sensor data was recorded. Independent Component Analysis (ICA) was used as the BSS algorithm and the EMG recordings were decomposed into Independent Components (ICs) which were further processed with a windowed 250ms root mean square (RMS) smoothing filter as well as signal normalisation. The flex sensor data was used to generate synchronised literature-informed predicted EMG (pEMG) waveforms, representing the ideal EMG activation signals for each muscle. The muscle-specific pEMG waveforms were also processed with a 250ms RMS filter and signal normalisation before signal comparisons were made using Pearson’s correlation against all pICs. In each experimental run, the pIC with the highest calculated Pearson’s correlation coefficient (r) value for each pEMG waveform was initially selected as the representative IC (rIC) for that muscle. A rIC selection algorithm was also developed which reassigned pICs that were selected to represent multiple muscles to ensure each muscle was assigned a unique rIC. A case study was conducted to evaluate the effects of the investigated movement protocol parameters upon which experimental guidelines were formed. Fisher-corrected mean population correlation coefficients (ρ) and 95% confidence intervals were calculated to evaluate the effects of timing, randomisation and anticipation of movements. Using an amalgamated population of all the experiments and experimental runs combined, the eight muscles investigated were isolated with ρ values greater than 0.65 indicating moderate isolation (defined as 0.60 ≤ ρ < 0.80), with the exception FDS-Index Band which was poorly isolated (ρ < 0.60) with a ρ value of 0.59. The data did, however, show high variability in all experiments indicating that the sample population was too small and was possibly influenced by poor performing participants. The Timing, Randomisation and Anticipation experiments showed no discernible effects across all participants on the ability of the sdEMG technique to detect and isolate the deep and superficial forearm muscles investigated. The Anticipation experiment also showed that participant reaction delays on average increased steadily during each experimental run suggesting the anticipated visual cues were too complex and potentially confused participants. Concise experimental sdEMG guidelines were developed in which the sdEMG technique was found to be robust to variations of the three movement protocol parameters investigated.

The waste of building energy consumption is a major challenge in the world. And the real-time detection of human thermal comfort is an effective way to meet this issue. As mentioned in name, it means to detect the human’s comfort level in real-time and non-invasively. However, due to the various factors such as individual difference of thermal comfort, elements related to climatic (temperature, humidity, illumination, etc.) and so on, there is still a long way to implement this strategy in real life. From another perspective, the current HVAC (heating, ventilating and air-conditioning) systems cannot provide flexible interaction channels to adjust atmosphere, and naturally fails to satisfy requirements of users. All of them indicate the necessity to develop a detection method for human thermal comfort. In this paper, a non-invasion detection method toward human thermal comfort is proposed from two perspectives: macro human postures and skin textures. In posture part, OpenPose is used for analyzing the position coordinates of human body key points’ in images, for example, elbow, knee, and hipbone, etc. And the results of analyzing would be interpreted from the term of thermal comfort. In skin textures, deep neural network is used to predict the temperature of human skins via images. Based on Fanger’s theory of thermal comfort, the results of both parts are satisfying: subjects’ postures can be captured and interpreted into different thermal comfort level: hot, cold and comfort. And the absolute error of prediction from neurons network is less than 0.125 degrees centigrade which is the equipment error of thermometer used in data acquisition. With the solution proposed by this paper, it is promising to non-invasively detect the thermal comfort level of users from postures and skin textures. Finally, theconclusion and future work are discussed in final chapter.
Slöseriet med att bygga energiförbrukningen är en stor utmaning i världen. Ochdetektering av mänsklig termisk komfort i realtid är ett effektivt sätt att lösaproblemet. Som nämns i namn betyder det att detektera människans komfortnivå i realtid och icke-invasivt. På grund av de olika faktorerna som individuell skillnad i termisk komfort, är emellertid faktorer som är relaterade till klimat (temperatur, luftfuktighet, belysning etc.) det fortfarande en lång väg att implementera denna strategi i verkligheten. Från ett annat perspektiv kan nuvarande system för uppvärmning, ventilation och luftkonditionering inte tillhandahålla flexibla interaktionskanaler för att anpassa atmosfären och naturligtvis misslyckas till nöjda krav från användarna. Alla indikerar nödvändigheten av att utveckla en detekteringsmetod för mänsklig termisk komfort. I detta dokument föreslås en ickeinvasion detekteringsmetod mot mänsklig termisk komfort från två perspektiv: makro mänskliga hållningar och hudtexturer. I hållningspartiet används OpenPose för att analysera positionskoordinaterna för kroppens huvudpunkter i bilder, till exempel armbåge, knä och höftben osv. Och resultaten av analysen skulle tolkas från termen av termisk komfort. I hudtexturer används djupt neuralt nätverk för att förutse temperaturen på mänskliga skinn via bilder. Baserat på Fangers teorin om värmekomfort är resultaten av båda delarna tillfredsställande: subjektens hållningar kan fångas och tolkas till olika värmekomfortnivåer: varm, kall och komfort. Och det absoluta felet av prediktering från neuronnätverket är mindre än 0,125 grader Celsius, vilket är utrustningsfelet hos termometern som används vid datainsamling. Med lösningar i detta papper är det lovande att detektera användarens värmekomfortnivå fritt från invändningar och hudtexturer. Slutligen diskuteras slutsatserna och detframtida arbetet i sista kapitlet.

The effectiveness of mild hyperthermia in improving the outcome of radiotherapy and chemotherapy treatment is well established for surface tumours (e.g. an average improvement of 20% in the 5 years survival rate using mild hyperthermia in conjunction with radiotherapy). However, to apply this technique to deep body solid tumours clinically, a non-invasive thermometry method is needed. Several approaches have been proposed for non-invasive thermometry in the past but none were capable of providing 3D temperature distributions in-vivo with the required accuracy. In this thesis, the potential for determining the temperature in a deep body solid tumour during mild hyperthermia by combining ultrasound propagation velocity and electrical impedance measurement techniques has been investigated. Simultaneous ultrasound propagation velocity and electrical impedance measurements were made in-vitro on liver, fat and layered fat-liver samples as the temperature was increased to mild hyperthermia levels (45°C max.). From the ultrasound measurements a linear correlation was found between the percentage of fat in the sample and the change in ultrasound propagation velocity with temperature (-0.12ms-1°C-1%-1, r2 = 0.93). Analysis of the data from the multi-frequency electrical impedance measurements showed that the magnitude of the electrical impedance measured at 256kHz normalised to the magnitude of the electrical impedance measured at 8kHz gave a linear correlation with the percentage of fat in the sample (0.003 %-1, r2 = 0.72) but no statistically significant correlation between the fat content and the temperature coefficient at 256kHz (r2 = 0.007, p >0.05). These results support an approach of using high to low frequency impedance ratios to determine the percentage of fat in the tissue and then this together with an ultrasound propagation velocity measure to detect the change in the temperature of the tissue. Application of this technique is limited by the variation in the change in ultrasound propagation velocity with temperature between tissue samples found in this study but the origins of this are unclear. In addition, further improvements in the spatial sensitivity of the tetrapolar impedance measurements are necessary to ensure an adequate spatial determination of fat content.

Orientadores: Cristina Laguna Benetti Pinto, Paulo César Giraldo
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-26T11:56:33Z (GMT). No. of bitstreams: 1 Mira_TicianaAparecidaAlvesde_M.pdf: 3039632 bytes, checksum: e71e393db6defef4a1b3ab3fdeaf8c6f (MD5) Previous issue date: 2015
Resumo: Introdução: Apesar dos tratamentos cirúrgico e medicamentoso utilizados para endometriose, muitas mulheres mantêm os sintomas álgicos. A literatura é escassa quanto a tratamentos complementares para dor. Objetivos: Avaliar a efetividade da TENS no tratamento complementar da dor pélvica crônica e dispareunia de profundidade em mulheres com endometriose profunda. Sujeitos e métodos: Ensaio controlado aleatorizado realizado no Departamento de Tocoginecologia da Universidade Estadual de Campinas. Foram incluídas 22 mulheres com endometriose profunda em uso de tratamento hormonal (progestagênios ou contraceptivo oral combinado), com persistência da queixa de dor pélvica crônica e/ou dispareunia de profundidade. Realizou-se aplicação da TENS por 8 semanas, com aleatorização das participantes em dois grupos: Grupo 1 - TENS modo acupuntura (Frequência: 8Hz, duração do pulso: 250µs e variação em intensidade e frequência (VIF) em 1ms) (n=11) e Grupo 2 - TENS autoaplicável (Frequência: 85Hz, duração do pulso: 75µs) (n=11); intensidade: ajustável "forte, mas confortável". Foram realizadas avaliações pré e pós-tratamento através da Escala Visual Analógica, Escala de Dispareunia de Profundidade, Questionário de Qualidade de Vida em Endometriose (EHP-30). Comparação pré e pós-tratamento através de teste de Wilcoxon e teste de Mann-Whitney. Resultado: As 22 mulheres com endometriose profunda utilizavam tratamento hormonal há 1,65±2,08 anos e mantinham queixa de dor pélvica e/ou dispareunia de profundidade. Os dois tipos de TENS, modo acupuntura e autoaplicável, promoveram melhora da dor pélvica crônica (p<.0001), dispareunia de profundidade (p=.0010) e qualidade de vida (p<.0001). Conclusões: Ambos os recursos (TENS modo acupuntura e TENS autoaplicável) demonstraram efetividade no tratamento complementar da dor pélvica crônica e dispareunia de profundidade e melhora da qualidade de vida de mulheres com endometriose profunda, independente do dispositivo utilizado para tratamento
Abstract: Introduction: Despite all the surgical and medical treatments for endometriosis many women have symptoms of pain. Nevertheless, the literature is scarce on additional treatments for pain. Objective: Evaluate the effectiveness of TENS applied as a complementary treatment of chronic pelvic pain and deep dyspareunia in women with deep endometriosis. Subjects and Methods: Randomized controlled trial conducted at the Department of Obstetrics and Gynecology of the University of Campinas. Twenty-two women were included and they presented deep endometriosis and made use of hormonal treatment (progestin or combined oral contraceptive) with persistent complaints of chronic pelvic pain and/or deep dyspareunia. TENS application for 8 weeks was applied with randomization of participants into two groups: Group 1 - TENS like acupuncture (frequency: 8 Hz, pulse duration: 250?s and variation in intensity and frequency (VIF) of 1 ms) (n = 11) and Group 2 - TENS self-applied (frequency: 85Hz, pulse duration: 75?s) (n = 11); intensity: Adjustable "strong but comfortable". Measurements by Visual Analogue Scale, Dyspareunia Depth Scale and Endometriosis Health Profile - Questionnaire (EHP-30) were performed pre and post treatment. To compare pre and post-treatment the Wilcoxon test and Mann-Whitney test were used. Results: The twenty-two women with deep endometriosis used hormonal treatment for 1.65±2.08 years and kept complaining about pelvic and / or deep dyspareunia pain. The two types of TENS (acupuncture and self-applied) promoted improvement in chronic pelvic pain (p <.0001), deep dyspareunia (p = .0010) and quality of life (p <.0001). Conclusion: Both features (TENS like acupuncture and TENS self-applied) demonstrated effectiveness as complementary treatment of chronic pelvic pain and deep dyspareunia and improved the quality of life of women with deep endometriosis regardless which one of the devices were used for treatment
Mestrado
Fisiopatologia Ginecológica
Mestra em Ciências da Saúde

Comparar a qualidade da imagem entre a ultrassonografia transvaginal sem preparo intestinal e após preparo intestinal nas pacientes com suspeita de endometriose infiltrativa profunda do compartimento posterior e avaliar do grau de desconforto das pacientes em relação ao preparo intestinal. Estudo transversal com dados coletados prospectivamente, incluindo 39 pacientes com suspeita clínica de endometriose do compartimento posterior do ambulatório de Endometriose do Hospital Universitário Pedro Ernesto (HUPE) da Universidade do Estado do Rio de Janeiro (UERJ), no Rio de Janeiro. As pacientes foram submetidas à ultrassonografia transvaginal (USTVG) sem preparo intestinal prévio, seguido de nova USTVG uma hora após realização do enema retal. Os vídeos dos exames gravados foram editados, com ênfase na avaliação do compartimento posterior, com interesse na identificação do nódulo retrocervical e do retossigmóide. Foram graduados conforme a qualidade da imagem pelo examinador e por um radiologista (ambos mascarados), que marcaram uma nota de 0 a 10, usando a escala analógica visual. Restaram apenas 26 pacientes. Em relação ao desconforto devido a realização do enema retal, todas pacientes (100%) relataram apenas um desconforto discreto. Conforme a opção escolhida pelos avaliadores em relação ao melhor método, eles concordaram em 13 (50%) pacientes que a ultrassonografia transvaginal com preparo retal é melhor. Foi usado o teste não-paramétrico de Wilcoxon para amostras dependentes. O p-valor obtido foi de 0.042, considerado significativo (abaixo de 0.05). Isto significa que a realização do enema retal antes da realização da ultrassonografia transvaginal proporcionou uma qualidade melhor na avaliação dos nódulos. A diferença entre as avaliações com e sem preparo retal é maior nos nódulos menores que 2cm, porque encontramos a diferença de 1,1 entre os valores das medianas dos dois tipos de exames. Nos nódulos maiores que 2cm, a diferença encontrada foi de apenas 0,65. A realização do enema retal previamente à realização da ultrassonografia transvaginal no diagnóstico do nódulo endometriótico mostra uma melhora discretamente significativa na qualidade da imagem, comparativamente a não realização de preparo intestinal prévio. Somente nos casos onde o nódulo era menor que 2 cm, foram encontrados valores estatisticamente significativos com o preparo retal. O enema retal causa discreto desconforto, porém isto não parece ser um fator limitante na realização da ultrassonografia com preparo intestinal.
To compare image quality between the transvaginal ultrasound without bowel preparation and after bowel preparation in patients with suspected deep infiltrating endometriosis of the posterior compartment and evaluate the degree of discomfort of patients in relation to bowel preparation. Cross sectional data collected prospectively, including 39 patients with clinical suspicion of endometriosis of the posterior compartment of the endometriosis clinic of the Hospital Universitário Pedro Ernesto (HUPE) State University of Rio de Janeiro (UERJ), in Rio de Janeiro . The patients underwent transvaginal sonography (USTVG) without prior bowel preparation, followed by new USTVG one hour after completion of the rectal enema. The recorded videos of the tests were published, with emphasis on evaluation of the posterior compartment, with interest in the identification of the nodule retrocervical and rectosigmoid. Were graded according to the quality of the image by the examiner and by a radiologist (both masked), which marked a score from 0 to 10, using the visual analog scale. That left only 26 patients. Regarding the realization of discomfort due to rectal enema, all patients (100%) reported only mild discomfort. Depending on the option chosen by the evaluators regarding the best method, they agreed in 13 (50%) patients with transvaginal ultrasound rectal preparation is better. We used the nonparametric Wilcoxon test for dependent samples. The p-value obtained was 0042 and considered significant (less than 0.05). This means that the completion of rectal enema prior to the transvaginal ultrasound provided a better quality in the evaluation of nodules. The difference between evaluations with and without rectal preparation is higher in nodules smaller than 2 cm, because we found a difference of 1.1 between the median values of the two types of tests. In nodules larger than 2cm, the difference was only 0.65. The performance of the rectal enema prior to the performance of transvaginal sonography in the diagnosis of endometriotic nodule shows a slightly significant improvement in image quality, compared to non-completion of bowel preparation prior. Only in cases where the lump was less than 2 cm were found statistically significant values with rectal preparation. The rectal enema cause mild discomfort, but this does not seem to be a limiting factor in the performance of ultrasound with bowel preparation

This thesis proposes a novel guidance concept for autonomous surgical robots using ultrasound imaging and advanced artificial intelligence techniques. Automatic real-time interpretation of the images acquired during the operations allows the robots to navigate the surgical space safely and identify the target anatomy correctly. In particular, automatic image quality assessment, outlining and tracking structures and tools, and uncertainty management were implemented in a surgical platform. The first application on the knee through cadaver and volunteer studies showed the feasibility and produced results comparable to clinical standards.

L'endométriose concerne 8 à 10% des femmes en âge de procréer et est responsable de douleurs pelviennes chroniques et d'infertilité. Seule l'exérèse chirurgicale des lésions permet un traitement curatif de la maladie. Dans le cas de l'endométriose profonde avec atteinte rectale la chirurgie est extensive et associée à une morbidité significative. Les traitements médicaux reposent sur une hormonothérapie visant à bloquer la fonction ovarienne dont l'effet n'est que suspensif et transitoire. Il n'existe à ce jour aucun traitement ciblant les mécanismes à l'origine de la maladie. L'objectif de notre travail était d'explorer différents mécanismes potentiellement impliqués dans le développement de la maladie et d'identifier des molécules capables d'intervenir sur ces mécanismes. Dans un premier temps nous avons exploré le phénotype hyperprolifératif des cellules endométriosiques profondes et cherché un lien avec différentes voies métaboliques impliquées dans la prolifération cellulaire telles que le stress oxydant, la voie ERK et la voie Akt. Dans un deuxième temps, nous avons exploré le recrutement des cellules endométriales au sein de la cavité péritonéale au travers de l'interaction CXCR4-CXCL12. Des cultures cellulaires ont été réalisées à partir de prélèvements humains de nodules endométriosiques profonds, d'endomètre eutopique et d'endomètre sain. Des lames histologiques ont été préparées à partir de nodules endométriosiques profonds. Des prélèvements de liquide péritonéal de femmes endométriosiques et de témoins ont été congelés. La prolifération cellulaire a été étudiée par incorporation de thymidine tritiée. La production des FRO a été évaluée par spectrofluorimétrie. La voie ERK a été évaluée par western blot, ELISA et immunohistochimie. La voie Akt été évaluée par western blot et immunohistochimie. Nous avons montré un phénotype hyperprolifératif des cellules endométriosiques profondes en rapport avec une activation de la voie ERK par le biais du stress oxydant et à une activation de la voie Akt. Nous avons montré qu'un anti-oxydant (NAC), un inhibiteur de protéines kinases (A771726), un inhibiteur de Raf (sorafenib), un inhibiteur de mTOR (temsirolimus), un agoniste des cannabinoïdes (WIN 55212-2) et un anti-métabolite (5-FU) pouvaient contôler la prolifération des cellules endométriosiques profondes in vitro et la progression de nodules endométriosiques profonds implantés dans des souris Nudes. L'interaction CXCR4-CXCL12 a été étudiée par western blot, analyse de migration, cytométrie de flux et ELISA. Nous avons montré une attraction spécifique des cellules endométriosiques profondes sur-exprimant le CXCR4 par la chimiokine CXCL12 présente en quantité accrue dans le liquide péritonéal des femmes endométriosiques. En conclusion, nous avons montré que le traitement médical de l'endométriose pouvait être non hormonal et que le stress oxydant, la voie ERK et la voie Akt constituaient de nouvelles pistes thérapeutiques à évaluer dans le cadre d'essais cliniques. Nous avons également montré comment la modification constitutive des cellules de l'endomètre eutopique pouvait favoriser leur recrutement dans la cavité péritonéale.

INTRODUÇÃO: Apesar de a endometriose profunda (EPF) ser a forma da doença de maior repercussão clínica, os estudos sobre a doença costumam ser baseados em lesões de endometriose ovariana (EOV) e peritoneal (EPT). A patogênese da EPF ainda é objeto de amplo debate, pois há poucos estudos feitos exclusivamente com lesões de EPF. O fator de transcrição codificado pelo gene homeobox A10 (HOXA10) regula a conferência de identidade tecidual de útero ao ducto paramesonéfrico indiferenciado durante o período embrionário. O gene mantém um padrão de expressão temporal e espacial bem definido e, durante a fase adulta, continua expresso no miométrio e endométrio. Sugere-se que HOXA10 esteja implicado na patogênese da endometriose, pois é expresso em EOV, EPT, endometriose pulmonar e endometriose retovaginal, um tipo de EPF. Possivelmente, o gene HOXA10 seja necessário para conferir identidade de endometriose a um tecido indiferenciado. O estradiol e a progesterona ativam a transcrição do gene HOXA10 e regulam diretamente sua ação. Esses hormônios estão envolvidos na patogênese da EPF, e suas atividades podem ser inferidas pelo estudo da expressão tecidual de seus receptores. A endometriose de reto-sigmoide (ERS) é um modelo representativo para o estudo da EPF. Neste estudo, avaliamos a expressão proteica do fator de transcrição HOXA10, das isoformas ? (ER-alfa) e beta (ER-beta) dos receptores de estrogênio, e do receptor de progesterona AB (PR-AB) e sua isoforma B (PR-B) na lesão (LES) e no tecido muscular liso perilesional (TMLP) de ERS de pacientes inférteis, durante as fases proliferativa e secretora do ciclo menstrual. MÉTODOS: amostras de LES e TMLP de ERS de 18 pacientes (9 operadas em cada fase do ciclo menstrual) foram agrupadas em blocos de microarranjos de tecidos (tissue microarray). As amostras foram coradas com anticorpos específicos para análise imunoistoquímica de cada uma das proteínas. Foram então avaliadas por microscopia ótica (MO) e pela análise das imagens digitalizadas das lâminas com por um software específico, a análise morfométrica (AM). RESULTADOS: HOXA10 foi expresso no estroma de LES de ERS durante a fase secretora, de acordo com a MO. ER-alfa e ER-betaforam expressos em glândulas e estroma de LES e TMLP de ERS durante ambas as fases do ciclo, de acordo com a MO e a AM. PR-AB e PR-B foram expressos em glândulas e estroma de LES de ERS durante ambas as fases do ciclo, de acordo com a MO. PR-B foi mais expresso durante a fase secretora, independentemente do local de expressão, segundo a AM. A expressão de HOXA10 correlacionou-se diretamente com PR-AB e PR-B na ERS, segundo a AM. Não houve correlação entre ER-alfa e ER-beta com HOXA10, PR-AB ou PR-B em nenhuma fase do ciclo ou local de expressão de ERS. CONCLUSÕES: HOXA10 é expresso em ERS, um local fora do seu eixo espacial de expressão. A presença de HOXA10 pode ser necessária para conferir a identidade \"de novo\" na EPF, incluindo ERS. A progesterona pode ativar o gene HOXA10 e regular esta ação, possivelmente mediada por PR-B. O estradiol exerce sua ação mitógena na ERS através ER-alfa e ER-beta
INTRODUCTION: Although deep endometriosis (DE) is the major clinical form of endometriosis, studies regarding the disease are typically based on ovarian (OE) and peritoneal (PE) lesions. DE pathogenesis is still a matter of great discussion because there are few studies exclusively involving DE lesions. The transcription factor encoded by the homeobox gene A10 (HOXA10) regulates the identity imparted to the undifferentiated paramesonephric duct during embryogenesis. The gene is expressed in the myometrium and endometrium during adult life in a well-defined spatial and temporal mode. It has been suggested that HOXA10 plays a role in endometriosis pathogenesis because it is expressed in OE, PE, pulmonary endometriosis, and rectovaginal endometriosis, which is a clinical form of DE. Thus, HOXA10 may be necessary for \"de novo\" endometrial development from undifferentiated tissues. Both estradiol and progesterone activate HOXA10 transcription and directly regulate its action. These hormones are involved in DE pathogenesis, and therefore their activities could be assessed by studying the tissue expression of their receptors. Rectosigmoid endometriosis (RE) is a representative model for studying DE. In this study, we evaluated the protein expression of HOXA10, the estrogen receptor (ER) isoforms alfa (ER-alfa) and beta (ER-beta), the progesterone receptor AB (PR), and the PR isoform B (PR-B) in lesions (LES) and adjacent smooth muscle (SM) of RE from infertile patients during the proliferative and secretory phases of the menstrual cycle. METHODS: LES and SM samples from RE patients were grouped in tissue microarray blocks. Each of the proteins was analyzed by immunohistochemistry using regular optical microscopy (OM) and a software-assisted analysis of digitalized images as well as morphometric analysis (MA). RESULTS: HOXA10 was expressed in the stroma of the LES during the secretory phase based on OM. ER-alfa and ER-beta were expressed in the glands and stroma of LES and SM during both phases based on OM and MA. PR and PR-B were expressed in the glands and stroma of LES during both phases; however, PR-B had higher expression during the secretory phase, independent of its expression in the LES or SM. HOXA10 expression was directly correlated with PR and PR-B expression in RE. In addition, there was no correlation between the expression of ER-alfa and ER-beta with HOXA10, PR, or PR-B during any phase of the menstrual cycle or site of expression. CONCLUSIONS: HOXA10 is expressed in RE outside of its spatial domain of expression, and may be necessary for \"de novo\" development of DE, including RE. Progesterone might stimulate HOXA10 expression and regulate this action, which is most likely mediated by PR-B. Moreover, estradiol exerts its mitogenic effect in RE though ER-alfa and ER-beta

The treatment of deep carious lesions (DCLs) represents a challenge for dentists, as these lesions require removal of dentin in proximity to the pulp that represents a higher risk of ending in pulp exposure. There is increasing evidence supporting minimally invasive caries removal methods, such as stepwise excavation procedure (SWP), instead of non-selective (complete) dentin caries removal for the treatment of DCLs. However, recent research has indicated that dentists have not completely adopted less invasive caries removal methods for the management of DCLs. These studies have been primarily conducted in Europe or South America; thus, few studies have been conducted in the United States to understand dentists’ management options of deep carious lesions in permanent teeth. Additionally, the proportion of dentists who would be willing to adopt less invasive carious tissue removal is unknown, especially in the United States. This dissertation consists of three studies that analyzed the effectiveness of SWP, the factors associated with success, an assessment of its costs and the acceptability of this treatment among U.S dentists. Study I assessed the patient factors predicting a successful SWP by retrospectively investigating a sample from the University of Iowa College of Dentistry from January 2004 through December 2012. Study I showed that SWPs showed a 75% success rate when evaluated within 36 months of the initial treatment. Patients who had a successful SWP treatment were slightly younger than patients whose SWP treatment was not successful. Study II performed a cost-effectiveness analysis by comparing SWP vs. the standard caries treatment (complete caries removal). Study II showed that SWP significantly reduced cost, resulting in an average savings of 64% compared to TCR over a 5-year period. Study III consisted of a statewide survey that contacted 1,434 Iowa dentists with the aim of identifying the most important factors that influence dentists’ decisions for DCLs treatment using conjoint analysis. From the total, 36.4% (n=522) clinicians answered the survey. One of the main study findings was that among the three factors (hardness of dentin, depth of the lesion and patient age) depth of the lesion was the most important factor influencing dentists’s decision when selecting a less invasive caries removal method. Study III did not find any significant association between years of practicing dentistry, type of practice and practice setting regarding being willing to select a less invasive caries removal method. In conclusion, this dissertation has demonstrated that the stepwise caries removal is a cost-saving and highly successful treatment for the management of deep caries lesions. Studies I and II have shown that this method has a high clinical success rate and less long-term treatment costs. Regarding the acceptability of SWP among clinicians, this dissertation has shown that most dentists in Iowa would consider less invasive caries methods for a DCL; however, these techniques have not been completely adopted and accepted among American dentists. Thus, dentists should be trained in less invasive caries methods, given instruction about which criteria they should use to assess a DCL, and provide them with the best evidence-based strategies for managing deep lesions. The findings of this dissertation should engage stakeholders to provide dentists with professional incentives for using these techniques. Specifically, our results support the idea that SWP minimizes costs while providing the appropriate patient care.

This research focuses on visualisation challenges associated with anatomical imaging of complex joints such as the human knee. Current imaging systems are inadequate to provide 3D perception and lack the level of situational awareness needed for performing highly complex minimally invasive surgeries like knee arthroscopy. As a result, unintended tissue damage is common occurrence and training new surgeons takes a very long time. To improve surgical precision and training, this study presents a series of novel methods and computational tools that provide 3D perception for safer surgery with added ability of automatically recognition of multiple tissue types in real time.

Alzheimer’s disease is the leading cause of dementia worldwide, affecting more than 30 million people. FDA-approved drugs only provide temporary relief to memory problems, and no disease-modifying therapies are currently available. As such, different therapeutic modalities are being investigated to address the biological and/or cognitive manifestations of the disease. A number of these therapies are highly invasive and require stereotactic surgery, potentially posing a greater risk of harms to a vulnerable population with cognitive deficits that limit their ability to provide fully informed consent. Using an interdisciplinary and pragmatic approach to bioethical inquiry, this dissertation examines studies on deep brain stimulation in people with Alzheimer’s disease, reviewing clinical trials and relevant animal studies to highlight pressing ethical concerns that ongoing and forthcoming trials need to address. By having three major publications during the course of the PhD as the main chapters, This thesis aims to enumerate ethical issues that encompass the genetic, neurobiological, cognitive, individual, and societal dimensions of deep brain stimulation for Alzheimer’s disease. These ethical considerations can then be extended into other forms of novel neurosurgical trials such as cell implantation and gene therapy. Finally, this thesis incorporates other publications during the PhD to illustrate further conundrums on the use of deep brain stimulation and highlight directions for future bioethics research on the use of invasive neurotechnologies for dementia in terms of the importance of genetic underpinnings, clinical translation issues, communication of research objectives, media portrayal, and implications on criminal responsibility.

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies
Tree species identification forms an integral part of biodiversity monitoring. Locating at-risk species and predicting their distribution is equally as important as tracing invasive alien plant species distributions. The high prevalence of the latter and their destructive impact on the environment is the focus for this thesis. In areas of the world where technology limitations are restrictive, an approach using low-cost, available RGB drone imagery is proposed to train advanced deep learning models to distinguish individual tree species; three dominant species (Pinus elliotti, Eucalyptus grandis and Syzygium cordatum) providing the bulk of sampling data, of which the first two are highly invasive in the region. This study explored the efficacy of utilizing Mask RCNN, an instance segmentation deep neural network, in identifying multiple classes of trees within the same image. In line with the low-cost approach, Google Colaboratory was utilized which drastically lowers the training time necessary and alleviates the need for high GPU systems. The model was trained on imagery from three study areas which were representative of three distinct landscapes: very dense forest, moderately dense forest with overlapping canopies, and open forest. The results indicate decent performance in open forest landscapes where overlapping tree crowns is infrequent with mean Average Precision of 0.71. On the contrary, in a dense forest landscape with many interlocking tree crowns, a mean Average Precision of 0.43 is highly indicative of the model’s poor performance in such environments. The trained network was also observed to have higher confidence scores of detected objects within the open forest study areas as opposed to dense forest.

L’accident thromboembolique veineux, tel que la thrombose veineuse profonde (TVP) ou thrombophlébite des membres inférieurs, est une pathologie vasculaire caractérisée par la formation d’un caillot sanguin causant une obstruction partielle ou totale de la lumière sanguine. Les embolies pulmonaires sont une complication mortelle des TVP qui surviennent lorsque le caillot se détache, circule dans le sang et produit une obstruction de la ramification artérielle irriguant les poumons. La combinaison d’outils et de techniques d’imagerie cliniques tels que les règles de prédiction cliniques (signes et symptômes) et les tests sanguins (D-dimères) complémentés par un examen ultrasonographique veineux (test de compression, écho-Doppler), permet de diagnostiquer les premiers épisodes de TVP. Cependant, la performance de ces outils diagnostiques reste très faible pour la détection de TVP récurrentes. Afin de diriger le patient vers une thérapie optimale, la problématique n’est plus basée sur la détection de la thrombose mais plutôt sur l’évaluation de la maturité et de l’âge du thrombus, paramètres qui sont directement corrélées à ses propriétés mécaniques (e.g. élasticité, viscosité). L’élastographie dynamique (ED) a récemment été proposée comme une nouvelle modalité d’imagerie non-invasive capable de caractériser quantitativement les propriétés mécaniques de tissus. L’ED est basée sur l’analyse des paramètres acoustiques (i.e. vitesse, atténuation, pattern de distribution) d’ondes de cisaillement basses fréquences (10-7000 Hz) se propageant dans le milieu sondé. Ces ondes de cisaillement générées par vibration externe, ou par source interne à l’aide de la focalisation de faisceaux ultrasonores (force de radiation), sont mesurées par imagerie ultrasonore ultra-rapide ou par résonance magnétique. Une méthode basée sur l’ED adaptée à la caractérisation mécanique de thromboses veineuses permettrait de quantifier la sévérité de cette pathologie à des fins d’amélioration diagnostique. Cette thèse présente un ensemble de travaux reliés au développement et à la validation complète et rigoureuse d’une nouvelle technique d’imagerie non-invasive élastographique pour la mesure quantitative des propriétés mécaniques de thromboses veineuses. L’atteinte de cet objectif principal nécessite une première étape visant à améliorer les connaissances sur le comportement mécanique du caillot sanguin (sang coagulé) soumis à une sollicitation dynamique telle qu’en ED. Les modules de conservation (comportement élastique, G’) et de perte (comportement visqueux, G’’) en cisaillement de caillots sanguins porcins sont mesurés par ED lors de la cascade de coagulation (à 70 Hz), et après coagulation complète (entre 50 Hz et 160 Hz). Ces résultats constituent les toutes premières mesures du comportement dynamique de caillots sanguins dans une gamme fréquentielle aussi étendue. L’étape subséquente consiste à mettre en place un instrument innovant de référence (« gold standard »), appelé RheoSpectris, dédié à la mesure de la viscoélasticité hyper-fréquence (entre 10 Hz et 1000 Hz) des matériaux et biomatériaux. Cet outil est indispensable pour valider et calibrer toute nouvelle technique d’élastographie dynamique. Une étude comparative entre RheoSpectris et la rhéométrie classique est réalisée afin de valider des mesures faites sur différents matériaux (silicone, thermoplastique, biomatériaux, gel). L’excellente concordance entre les deux technologies permet de conclure que RheoSpectris est un instrument fiable pour la mesure mécanique à des fréquences difficilement accessibles par les outils actuels. Les bases théoriques d’une nouvelle modalité d’imagerie élastographique, nommée SWIRE (« shear wave induced resonance dynamic elastography »), sont présentées et validées sur des fantômes vasculaires. Cette approche permet de caractériser les propriétés mécaniques d’une inclusion confinée (e.g. caillot sanguin) à partir de sa résonance (amplification du déplacement) produite par la propagation d’ondes de cisaillement judicieusement orientées. SWIRE a également l’avantage d’amplifier l’amplitude de vibration à l’intérieur de l’hétérogénéité afin de faciliter sa détection et sa segmentation. Finalement, la méthode DVT-SWIRE (« Deep venous thrombosis – SWIRE ») est adaptée à la caractérisation de l’élasticité quantitative de thromboses veineuses pour une utilisation en clinique. Cette méthode exploite la première fréquence de résonance mesurée dans la thrombose lors de la propagation d’ondes de cisaillement planes (vibration d’une plaque externe) ou cylindriques (simulation de la force de radiation par génération supersonique). DVT-SWIRE est appliquée sur des fantômes simulant une TVP et les résultats sont comparés à ceux donnés par l’instrument de référence RheoSpectris. Cette méthode est également utilisée avec succès dans une étude ex vivo pour l’évaluation de l’élasticité de thromboses porcines explantées après avoir été induites in vivo par chirurgie.
The venous thromboembolism such as the lower limb deep venous thrombosis (DVT) is a vascular pathology characterized by a blood clot formation that induces partial or total vessel lumen occlusion. Pulmonary embolism is a fatal complication of DVT where the clot detaches from the wall, circulates in the blood flow, and produces an obstruction of pulmonary arterial branches. The combination of clinical prediction rules (signs or symptoms) and blood tests (D-dimer testing) coupled to venous ultrasonography (i.e. compression ultrasonography, color Doppler) allows an accurate diagnosis of first DVT. Nevertheless, such clinical tools present poor results to detect recurrent thrombotic events. Then, in order to guide patients towards optimal therapy, the problem is no more to detect the presence of thrombus, but to evaluate its maturity and its age, which are correlated to their mechanical properties (e.g. elasticity, viscosity). The dynamic elastography (DE) has been recently proposed as a novel non-invasive imaging modality capable to characterize the quantitative mechanical properties of tissues. The DE is based on the analysis of acoustical parameters (i.e. velocity, attenuation, wave pattern) of low frequency (10-7000 Hz) shear waves propagating within the probed medium. Such shear waves generated by external vibration, or remotely using ultrasound beam focalisation (radiation force), were tracked using ultra-fast ultrasound or magnetic resonance imaging. A method based on DE and adapted to mechanical characterization of venous thrombosis may allow the quantification of diseases severity in order to improve the final diagnosis. This thesis presents the works related to the development and complete validation of a novel non-invasive elastography imaging method for the quantitative and reliable estimation of mechanical properties of venous thrombosis. In order to fulfil the main objective, it is first necessary to improve knowledge about mechanical behaviours of blood clot (coagulated blood) subjected to a dynamic solicitation similar to DE. The shear storage (elastic behaviour, G’) and loss (viscous behavior, G’’) moduli of porcine blood clots are measured by DE during the blood coagulation kinetics (at 70 Hz) and after completely coagulation (between 50 Hz and 160 Hz). These results are the first dynamic behaviour measurements of blood clots in such wide frequency range. The subsequent step consists in introducing an innovative reference instrument (« gold standard »), called RheoSpectris, dedicated to measure the hyper-frequency viscoelasticity (between 10 Hz and 1000 Hz) of materials and biomaterials. This tool is indispensable to validate new dynamic elastography techniques. A comparative study between RheoSpectris and classical rheometry is performed to validate the measurements on different materials (silicon, thermoplastic, biomaterials, gel). The excellent agreement between both technologies allows to conclude that RheoSpectris is a reliable instrument for mechanical measurements at high frequencies, which is not always possible with current tools. The theoretical basis of a novel elastographic imaging modality, labelled SWIRE (« shear wave induced resonance dynamic elastography ») is presented and validated on vascular phantoms. Such approach allows the characterization of mechanical properties of a confined inclusion (e.g. blood clot) from its resonance (displacement amplification) due to the propagation of judiciously oriented shear waves. SWIRE has also the advantage to amplify the vibration amplitude within the heterogeneity to help for its detection and segmentation. Finally, the method DVT-SWIRE ((« Deep venous thrombosis – SWIRE ») is adapted to the quantitative elasticity estimation of venous thrombosis in the context of clinical use. DVT-SWIRE exploits the first resonance frequency measured within the thrombosis during the plane (vibration of rigid plate) or cylindrical (simulating supersonic radiation force generation) shear waves propagation. The technique is applied on DVT phantoms and the results are compared to those given by the RheoSpectris reference instrument. This method is also used successfully in an ex vivo study for the elasticity assessment of explanted porcine thrombosis surgically induced in vivo.

As espécies invasoras são conhecidas pela sua rápida disseminação, originando perda de biodiversidade das zonas invadidas, tornando-se importante realizar a monitorização das áreas florestais para o controlo destas espécies. Esta dissertação apresenta uma arquitetura para a deteção da espécie invasora Acacia Longifolia em imagens aéreas, particularmente relevante em Portugal. A arquitetura inclui a captura de imagens aéreas através de veículos aéreos não tripulados (VANTs), o pré-processamento das imagens e a divisão do conjunto de dados em treino, validação e teste. Também inclui uma rede neuronal convolucional (RNC) treinada para a classificação automática desta espécie invasora, nas imagens aéreas adquiridas. Testaram-se duas configurações da RNC, cuja arquitetura difere na última camada responsável pela classificação de amostras com 100 x 100 píxeis, obtidas por uma janela deslizante ao longo das imagens capturadas. Uma das redes classifica segundo nove classes (e.g., Acacia L., Vegetação, Estrada), sendo que a classificação obtida é convertida numa classificação binária através da sua matriz de confusão, tendo apresentado uma taxa de acerto de 98.5% utilizando o conjunto de teste. O segundo modelo foi treinado para a classificação binária relativa à presença de Acácia L., alcançando-se um desempenho de 98.7%. Os resultados mostram que a multi-classificação não prejudica o desempenho na deteção da Acacia Longifolia e fornece ao VANT informação adicional relativa ao ambiente. Por último, desenvolveu-se uma abordagem para melhorar a taxa de acerto, recorrendo a um especialista para verificar as previsões do sistema, ponderando-se o benefício em melhorar o desempenho com o custo de chamar o especialista.
Invasive species are known for their rapid dissemination, involving the loss of biodiversity in affected areas, becoming important to monitor the forest areas in order to control these species. This dissertation presents an architecture for the detection of the invasive species Acacia Longifolia in aerial images, particularly relevant in Portugal. The architecture includes capturing aerial images through unmanned aerial vehicles (UAVs), preprocessing the images and splitting the data into training, validation and testing sets. It also includes a trained convolutional neuronal network for automatic species classification based on the acquired aerial images. Two models were built, whose architecture differs in the last layer responsible for classifying samples with 100 x 100 pixels, obtained by a sliding window along the high-resolution images. One of the networks classifies according to nine classes (e.g., Acacia L., Vegetation, Roadway), and the obtained classification is then converted into a binary classification through the confusion matrix, having an accuracy of 98.5% for testing set. The second model was trained for binary classification for the presence of Acacia L., achieving an accuracy of 98.7% for the test set. The results show that the multi-classification does not hamper the performance of Acacia Longifolia detection and provides UAV with additional environmental information. Finally, an approach has been developed to improve the accuracy of the system by calling an expert to review the predictions produced by the system, balancing the expected benefit of accuracy improvement with the cost of calling the expert.