As úlceras venosas representam um grande problema de saúde mundial e elevados custos associados ao tratamento a longo prazo. A terapia ultrassônica tem sido aplicada por décadas a fim de acelerar o processo de cicatrização de feridas crônicas. Muitos autores observaram os efeitos do ultrassom pulsado de baixa intensidade (LIPUS) em úlceras venosas, no entanto não há dados concisos sobre os modos de aplicação. O objetivo deste estudo foi avaliar a eficácia de duas técnicas de aplicação (borda e leito) do LIPUS, comparada à terapia convencional (creme sulfadiazina de prata 1%) na cicatrização de úlceras venosas crônicas. Para tanto, vinte e quatro pacientes com úlceras venosas foram avaliados no Ambulatório de Úlceras da Dermatologia (AUD) do Centro Saúde Escola (CSE) da Faculdade de Medicina de Ribeirão Preto (FMRP) da Universidade de São Paulo (USP) e alocados aleatoriamente nos: Grupo Borda (média da idade 63 anos; 37,5% mulheres; e 62,5% brancas) com 9 úlceras (13,49 \'+ OU -\' 14,41 \'CM POT.2\' inicial) tratadas com LIPUS (1,5 MHz, 30 mW/\'CM POT.2\') na borda; Grupo Leito (média da idade 73 anos; 100% mulheres; e 87,5% brancas) com 8 úlceras (15.61 \'+ OU -\' 13.36 \'CM POT.2\' inicial) tratadas com LIPUS no leito; e Grupo Sulfadiazina (média da idade 76 anos; 20% mulheres; e 40% brancas) com 7 úlceras (24,06 \'+ OU -\' 30,10 \'CM POT.2\' inicial) tratadas diariamente com creme sulfadiazina de prata 1%. Durante o tratamento, as úlceras foram fotografadas quinzenalmente e analisadas pelo software ImageJ a fim de se obter a área ulcerada e posterior Índice de Cicatrização da Úlcera (ICU) e Relação Esfácelo/Granulação (REG). No Grupo Leito foi realizada uma análise histopatológica (contagem de fibroblastos, células inflamatórias, vasos sanguíneos e colágeno) a partir de biópsias coletadas no 1º e no 45º dia de tratamento. Os dados foram analisados pelo teste de efeitos mistos e por Poisson a fim de comparar os grupos, com um nível de significância de 95% (p < 0,05). Assim, considerando as discretas diferenças encontradas no ICU e na REG dos dois grupos irradiados somadas às alterações histopatológicas do GL, torna-se evidente a ação positiva do LIPUS no tratamento das úlceras venosas crônicas superior à terapia com sulfadiazina de prata 1%, independente do local de aplicação. / Venous ulcers represent a major health problem in the world and high costs associated with long-term treatment. Ultrasonic therapy has been applied for decades to enhance the process of chronics wound healing. Many authors have assessed the effects of LIPUS on venous ulcers, but there were no data about the different application techniques. This study aimed to assess the effectiveness of two application techniques (edge and bed) of LIPUS, comparing with the conventional therapy (1% silver sulfadiazine cream) on the chronic venous ulcers healing. Therefore, twenty four patients with venous ulcers were evaluated at the Ulcers Outpatient of Dermatology at the Teaching Health Center, Faculty of Medicine of Ribeirão Preto - University of São Paulo (FMRP-USP) and randomly allocated, as follows: Edge Group (mean age 62.9 years, 37.5% women, 62.5% white) with nine ulcers (13,49 \'+ OR -\' 14,41 \'CM POT.2\') treated with LIPUS (1.5 MHz, 30 mW/\'CM POT.2\') at the edge, Bed Group (mean age 72.6 years, 100% women, 87.5% white) with eight ulcers (15.61 \'+ OR -\' 13.36 \'CM POT.2\') treated with the same LIPUS at the bed and Sulfadiazine Group (mean age 75.7 years, 20% women, 40% white) with seven ulcers (24,06 \'+ OR -\' 30,10 \'CM POT.2\') treated daily with 1% silver sulfadiazine cream. During treatment, they were photographed every fifteen days and analyzed with the software ImageJ to obtain the ulcerated area, Wound Healing Index (WHI) and Sphacel and Granulation Ratio (SGR) from all ulcers. At the Bed Group, it was performed a histopathological analysis (fibroblasts, inflammatory cells, blood vessels, and collagen counting) from biopsies collected at the 1st and the 45th treatment day. Data were analyzed by the (mixed effects and Poisson tests) for comparison among groups, with the level of significance set at 95% (p < 0.05). Thus, considering the slight differences found in ICU and REG of irradiated groups and GL histopathological changes, it is evident better effects in chronic venous ulcers with LIPUS treatment than conventional therapy with silver sulfadiazine 1%, independently of application site.

Les ultrasons focalisés permettent d’effectuer des traitements thérapeutiques ciblés dans le corps humain. Dans le domaine des applications cardiovasculaires, ils permettent de détruire des caillots sanguins susceptibles de se former dans le système vasculaire. Dans ce cas, les mécanismes de thrombolyse sont largement liés à la cavitation ultrasonore, dont la dynamique complexe reste un obstacle à l’élaboration d’un dispositif thérapeutique. Dans le cadre de cette thèse, un système permettant le contrôle temporel de l’activité de cavitation en régime pulsé a été développé puis caractérisé. Ce dispositif utilise un transducteur focalisé et un hydrophone avec une boucle de rétroaction pour réguler l’activité de cavitation. Alors qu’en régime non régulé l’activité de cavitation a un caractère très aléatoire, le système de régulation mis au point permet d’atteindre un niveau de cavitation souhaité de manière très reproductible et avec une bonne stabilité temporelle. L’application de ce dispositif à la thrombolyse ultrasonore a été testée in vitro sur des caillots de sang humain. Au dispositif précédent a été ajouté un système permettant de déplacer le caillot sanguin au niveau du foyer, ainsi qu’un conduit permettant de compter le nombre de fragments libérés par la destruction du caillot. En comparaison des essais en régime non régulé, les essais en régime régulé ont montré une excellente efficacité thrombolytique et une très bonne reproductibilité, tout en diminuant les intensités acoustiques utilisées pour lyser les caillots sanguins. En parallèle des essais in vitro, une campagne de thrombolyse ultrasonore in vivo a été mise en place afin de réaliser des essais sur un modèle animal d’ischémie aiguë de membre inférieur. Un dispositif ultrasonore extracorporel in vivo guidé par échographie et monté sur un bras robotisé 6 axes a été développé. Un modèle ovin de thrombose artérielle a également été développé. Les tests ont permis de valider, d’une part, la faisabilité du modèle de caillot artériel et, d’autre part, le concept de thrombolyse extracorporelle purement ultrasonore basée sur la cavitation inertielle régulée / Focused ultrasound can be used for therapeutic applications in the human body. In cardiovascular applications, they can destroy blood clots formed in the vascular system. In this case, thrombolysis mechanisms are related to ultrasonic cavitation, but the complex dynamics remains an obstacle to the development of a therapeutic device. In this thesis, a system for the temporal control of the pulsed cavitation activity has been developed and characterized. This device uses a focused transducer and a hydrophone with a feedback loop for regulating the cavitation activity. While cavitation activity has a random behaviour in non-regulated conditions, the control system developed achieves a desired level of cavitation with very reproducibly and with good temporal stability. The application of this device to the ultrasound thrombolysis was tested in vitro on human blood clots. In the previous device was added a system for moving the blood clot at the focal point, and a tube for counting the number of fragments released by the destruction of the clot. In comparison to uncontrolled regime, tests showed an excellent thrombolytic efficacy and a very good reproducibility, with reduced acoustic intensities. In parallel to the in vitro tests, ultrasound thrombolysis was tested in vivo on an animal model of acute limb ischemia. An extracorporeal ultrasound device, guided by ultrasound and mounted on a robotic arm, has been developed for in vivo investigation. An ovine model of arterial thrombosis has also been developed. Tests were used to validate the feasibility of the model of arterial clots and to validate in vivo the concept of purely ultrasonic extracorporeal thrombolysis based on inertial cavitation regulation system

As úlceras venosas representam um grande problema de saúde mundial e elevados custos associados ao tratamento a longo prazo. A terapia ultrassônica tem sido aplicada por décadas a fim de acelerar o processo de cicatrização de feridas crônicas. Muitos autores observaram os efeitos do ultrassom pulsado de baixa intensidade (LIPUS) em úlceras venosas, no entanto não há dados concisos sobre os modos de aplicação. O objetivo deste estudo foi avaliar a eficácia de duas técnicas de aplicação (borda e leito) do LIPUS, comparada à terapia convencional (creme sulfadiazina de prata 1%) na cicatrização de úlceras venosas crônicas. Para tanto, vinte e quatro pacientes com úlceras venosas foram avaliados no Ambulatório de Úlceras da Dermatologia (AUD) do Centro Saúde Escola (CSE) da Faculdade de Medicina de Ribeirão Preto (FMRP) da Universidade de São Paulo (USP) e alocados aleatoriamente nos: Grupo Borda (média da idade 63 anos; 37,5% mulheres; e 62,5% brancas) com 9 úlceras (13,49 \'+ OU -\' 14,41 \'CM POT.2\' inicial) tratadas com LIPUS (1,5 MHz, 30 mW/\'CM POT.2\') na borda; Grupo Leito (média da idade 73 anos; 100% mulheres; e 87,5% brancas) com 8 úlceras (15.61 \'+ OU -\' 13.36 \'CM POT.2\' inicial) tratadas com LIPUS no leito; e Grupo Sulfadiazina (média da idade 76 anos; 20% mulheres; e 40% brancas) com 7 úlceras (24,06 \'+ OU -\' 30,10 \'CM POT.2\' inicial) tratadas diariamente com creme sulfadiazina de prata 1%. Durante o tratamento, as úlceras foram fotografadas quinzenalmente e analisadas pelo software ImageJ a fim de se obter a área ulcerada e posterior Índice de Cicatrização da Úlcera (ICU) e Relação Esfácelo/Granulação (REG). No Grupo Leito foi realizada uma análise histopatológica (contagem de fibroblastos, células inflamatórias, vasos sanguíneos e colágeno) a partir de biópsias coletadas no 1º e no 45º dia de tratamento. Os dados foram analisados pelo teste de efeitos mistos e por Poisson a fim de comparar os grupos, com um nível de significância de 95% (p < 0,05). Assim, considerando as discretas diferenças encontradas no ICU e na REG dos dois grupos irradiados somadas às alterações histopatológicas do GL, torna-se evidente a ação positiva do LIPUS no tratamento das úlceras venosas crônicas superior à terapia com sulfadiazina de prata 1%, independente do local de aplicação. / Venous ulcers represent a major health problem in the world and high costs associated with long-term treatment. Ultrasonic therapy has been applied for decades to enhance the process of chronics wound healing. Many authors have assessed the effects of LIPUS on venous ulcers, but there were no data about the different application techniques. This study aimed to assess the effectiveness of two application techniques (edge and bed) of LIPUS, comparing with the conventional therapy (1% silver sulfadiazine cream) on the chronic venous ulcers healing. Therefore, twenty four patients with venous ulcers were evaluated at the Ulcers Outpatient of Dermatology at the Teaching Health Center, Faculty of Medicine of Ribeirão Preto - University of São Paulo (FMRP-USP) and randomly allocated, as follows: Edge Group (mean age 62.9 years, 37.5% women, 62.5% white) with nine ulcers (13,49 \'+ OR -\' 14,41 \'CM POT.2\') treated with LIPUS (1.5 MHz, 30 mW/\'CM POT.2\') at the edge, Bed Group (mean age 72.6 years, 100% women, 87.5% white) with eight ulcers (15.61 \'+ OR -\' 13.36 \'CM POT.2\') treated with the same LIPUS at the bed and Sulfadiazine Group (mean age 75.7 years, 20% women, 40% white) with seven ulcers (24,06 \'+ OR -\' 30,10 \'CM POT.2\') treated daily with 1% silver sulfadiazine cream. During treatment, they were photographed every fifteen days and analyzed with the software ImageJ to obtain the ulcerated area, Wound Healing Index (WHI) and Sphacel and Granulation Ratio (SGR) from all ulcers. At the Bed Group, it was performed a histopathological analysis (fibroblasts, inflammatory cells, blood vessels, and collagen counting) from biopsies collected at the 1st and the 45th treatment day. Data were analyzed by the (mixed effects and Poisson tests) for comparison among groups, with the level of significance set at 95% (p < 0.05). Thus, considering the slight differences found in ICU and REG of irradiated groups and GL histopathological changes, it is evident better effects in chronic venous ulcers with LIPUS treatment than conventional therapy with silver sulfadiazine 1%, independently of application site.