In einem von der Sächsischen Aufbaubank geförderten Verbundprojekt wird ein neuartiges Ultraschall-Behandlungsgerät entwickelt, das an der Klinik für Dermatologie und Allergologie des Krankenhauses Dresden- Friedrichstadt, einem Akademischen Lehrkrankenhaus der TU Dresden, im Rahmen einer klinischen Studie getestet wird. Durch die Messung peripherer topischer Durchblutungsparameter im Wundbereich unter dem Einfluss von niederfrequentem Ultraschall soll zur Objektivierung ablaufender Gewebeprozesse beigetragen werden. Das Ultraschall- Behandlungsgerät wurde gemeinsam vom Fraunhofer Institut für Werkzeugmaschinen und Umformtechnik Dresden, dem IMM Ingenieurbüro Mittweida sowie der Smart Material GmbH Dresden entwickelt / Within the framework of a cooperative project funded by Sächsische Aufbaubank, a new kind of ultrasound therapy system is under development and is being tested in clinical trials at the Department of Dermatology and Allergology at Dresden-Friedrichstadt Hospital, a university teaching hospital of Technische Universität Dresden. The measuring of peripheral topical parameters concerning blood circulation in wound areas under the influence of low-frequency ultrasound is expected to contribute to objectification of the relevant tissue processes. The ultrasound therapy system has been jointly developed by the Fraunhofer Institute for Machine Tools and Forming Technology, IMM Engineering Mittweida and Smart Material GmbH Dresden.

Rationale: The use of ultrasound as an adjuvant to conservative treatment for neck pain is common, but the evidence of its benefit remains unclear. Objective: To determine the effectiveness of ultrasound as an adjuvant to exercise or/and manual therapy for the improvement of patient-centered outcomes in adults with non-specific neck pain. Methods: Electronic databases including MEDLINE, EMBASE, AMED, CINAHL, CENTRAL, PEDro and PubMed were searched from date of inception to March 2019 for controlled trials involving ultrasound or phonophoresis as an adjuvant to exercise or/and manual therapy in adults with non-specific neck pain. Review Manager 5.3 was used to calculate mean group differences. Main results: Six studies (361 participants) examining ultrasound or phonophoresis as an adjuvant to exercise or/and manual therapy for sub-acute and chronic non-specific neck pain were included. The quality of evidence was of very low GRADE. Phonophoresis with capsaicin plus exercise improved pain immediately post-treatment (MD -3.30, 95% CI: -4.05 to -2.55) but not with diclofenac sodium plus exercise as compared to exercise alone. Continuous ultrasound plus exercise improved pain and Pressure Pain Threshold (PPT) at immediate post-treatment (pain: MD -3.42, 95% CI: -4.08 to -2.7; PPT: MD 0.91, 95% CI: 0.68 to 1.14 ) and at intermediate - term (pain: MD -2.70 95% CI: -3.62 to -1.78; PPT: MD 0.27 95% CI: 0.03 to 0.51) as compared to exercise alone. Continuous ultrasound or High Power Pain Threshold (HPPT) ultrasound plus manual therapy and exercise showed no benefit for pain reduction (MD -0.75, 95% CI: -2.08 to 0.58), increase in PPT (MD -1.15, 95% CI: -2.55 to 0.25) or improved function/disability (MD -1.05, 95% CI: -4.27 to 2.17) at immediate or short-term as compared to manual therapy and exercise. Conclusion: Based on very low quality evidence, there is insufficient data to support ultrasound or phonophoresis as an adjuvant treatment for non-specific neck pain. / Thesis / Master of Science Rehabilitation Science (MSc) / Ultrasound therapy is widely used with exercise or manual therapy for the treatment of neck pain. Yet, its benefits are not clear. This review looked at the benefits of ultrasound added to exercise, manual therapy or both for the treatment of neck pain. The review contains six studies with 361 participants who suffered from neck pain. The results showed very low quality evidence. Applying capsaicin cream with ultrasound or continuous ultrasound in conjunction with exercise had some benefit for improving pain. The same treatment did not improve function as compared to exercise alone. There was no benefit in improving pain or function by adding continuous or high power ultrasound to manual therapy and exercise compared to manual therapy and exercise alone. Due to very low quality evidence, we are uncertain of whether there is a benefit to adding ultrasound to exercise or/and manual therapy for treatment of neck pain.

Therapeutic efficacy of drugs depends on their ability to reach the treatment target. Drugs that exert their effect within cells are constrained by an inability to cross the cell membrane. Methods are being developed to overcome this barrier including biochemical and biophysical strategies. The application of ultrasound with microbubbles increases the permeability of cell membranes allowing molecules, which otherwise would be excluded, to enter the intracellular space of cells; a phenomenon known as sonoporation. This thesis describes studies aimed at improving our understanding of the mechanism underpinning sonoporation and of the exposure parameters affecting sonoporation efficiency. Cancer cells (KHT-C) in suspension were exposed to ultrasound and microbubbles – total of 97 exposure conditions. The effects on cells were assessed through uptake of cell-impermeable molecules (10 kDa to 2 MDa FITC-dextran), cell viability and microscopic observations of the plasma membrane using flow cytometry, colony assay and electron microscopy techniques. Sonoporation was a result of the interaction of ultrasound and microbubbles with the cell membrane. Disruptions (30-100 nm) were generated on the cell membrane allowing cell impermeable molecules to cross the membrane. Molecules up to 2 MDa in size were delivered at high efficiency (~70% permeabilisation). Sonoporation was short lived; cells re-established their barrier function within one minute, which allowed compounds to remain inside the cell. Following uptake, cells remained viable; ~50% of sonoporated cells proliferated. Sonoporation efficiency depended on ultrasound and microbubble exposure conditions. Microbubble disruption was a necessary but insufficient indicator of ultrasound-induced permeabilisation. The exposure conditions can be tailored to achieve a desired effect; cell permeability of ~70% with ~25% cell death versus permeability of ~35% with ~2% cell death. In addition, sonoporation depended on position in the cell cycle. Cells in later stages were more prone to being permeabilised and killed by ultrasound and microbubbles. This study indicated that sonoporation can be controlled through exposure parameters and that molecular size may not be a limiting factor. However, the transient nature may necessitate that the drug be in close vicinity to target cells in sonoporation-mediated therapies. Future work will extend the investigation into in vivo models.

Therapeutic efficacy of drugs depends on their ability to reach the treatment target. Drugs that exert their effect within cells are constrained by an inability to cross the cell membrane. Methods are being developed to overcome this barrier including biochemical and biophysical strategies. The application of ultrasound with microbubbles increases the permeability of cell membranes allowing molecules, which otherwise would be excluded, to enter the intracellular space of cells; a phenomenon known as sonoporation. This thesis describes studies aimed at improving our understanding of the mechanism underpinning sonoporation and of the exposure parameters affecting sonoporation efficiency. Cancer cells (KHT-C) in suspension were exposed to ultrasound and microbubbles – total of 97 exposure conditions. The effects on cells were assessed through uptake of cell-impermeable molecules (10 kDa to 2 MDa FITC-dextran), cell viability and microscopic observations of the plasma membrane using flow cytometry, colony assay and electron microscopy techniques. Sonoporation was a result of the interaction of ultrasound and microbubbles with the cell membrane. Disruptions (30-100 nm) were generated on the cell membrane allowing cell impermeable molecules to cross the membrane. Molecules up to 2 MDa in size were delivered at high efficiency (~70% permeabilisation). Sonoporation was short lived; cells re-established their barrier function within one minute, which allowed compounds to remain inside the cell. Following uptake, cells remained viable; ~50% of sonoporated cells proliferated. Sonoporation efficiency depended on ultrasound and microbubble exposure conditions. Microbubble disruption was a necessary but insufficient indicator of ultrasound-induced permeabilisation. The exposure conditions can be tailored to achieve a desired effect; cell permeability of ~70% with ~25% cell death versus permeability of ~35% with ~2% cell death. In addition, sonoporation depended on position in the cell cycle. Cells in later stages were more prone to being permeabilised and killed by ultrasound and microbubbles. This study indicated that sonoporation can be controlled through exposure parameters and that molecular size may not be a limiting factor. However, the transient nature may necessitate that the drug be in close vicinity to target cells in sonoporation-mediated therapies. Future work will extend the investigation into in vivo models.

Orientador: Sérgio Swain Muller / Banca: Nilton Mazer / Banca: Carlos Santos / Banca: Hamilton da Rosa Pereira / Resumo: O propósito deste estudo é determinar os efeitos do ultra-som terapêutico em baixa potência sobre a disco epifisial e o crescimento ósseo distal do fêmur e proximal da tíbia, em ratos jovens. Ratus Norvegicus com quatro semanas de vida, machos, totalizando 105 animais, foram submetidos à terapêutica de ultra-som (1,0 MHz, potência de 0,4 watt/cm2, cabeçote fixo, pulso contínuo, 10 minutos de duração, três ou quatro vezes por semana), na face medial do joelho direito. Um grupo de animais foi submetido a 30 aplicações de ultra-som, até a 13ª semana de vida e, outro a 45 aplicações, até a 18ª semana de vida. Os animais foram acompanhados até os seis meses. Foram estudadas as medidas do comprimento do fêmur e da tíbia e da largura das epífises distal do fêmur e proximal da tíbia e, a morfometria da altura do disco epifisial, como um todo e, de suas zonas histológicas. Os dados foram submetidos à análise de variância - fatorial inteiramente aleatorizado no nível de significância de 5%. Não foram encontradas diferenças significativas no crescimento ósseo longitudinal ou das larguras das epífises quando comparados lados direito e esquerdo nos grupos tratados (G1 e G2) e lado direito dos grupos tratados em relação ao respectivo controle (G3 e G4). Não houve diferença quando comparados os grupos tratados com 30 aplicações e 45 aplicações de ultra-som. A morfometria mostrou diferenças, somente na tíbia, em que tratado foi maior que controle, tanto para 30 quanto para 45 aplicações de ultra-som. Tratado foi maior do que controle, no disco epifisial, nos três momentos estudados; na zona de proliferação, somente na 13ª semana; e, na zona hipertrófica na 18ª e 26ª semanas. O ultra-som terapêutico, nas condições deste trabalho, não provocou alterações do comprimento... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The purpose of this study was to determining the effects of lowpower ultrasound therapy on the epiphyseal plate and the bone growth of the distal femur and the proximal tibia in young rats. One hundred five of four-week-old Rattus norvegicus males received ultrasound treatment of continuous therapeutic dose (1.0 MHz frequency, 0.4 watt/cm2, fixed probe, 10 minutes three or four times a week) on the medial face of the right knee. One group of animals underwent 30 ultrasound applications until the age of 13 weeks, and the other received 45 applications until the age of 18 weeks. The animals were followed up until they were six month old (26 weeks). Assessment included the measurement of the length of the femur and the tibia, the width of the femoral distal epiphysis and the proximal tibial epiphysis, and the morphometry of the reserve plus proliferative (Proliferative) and hypertrophic plus calcified hypertrophic (Hipertrophic) zones, as well as width of the epiphyseal plate. Totallyrandomized factorial variance analysis of the data was performed with significance level set at 5%. No significant differences were observed in longitudinal bone growth or epiphyseal width when right and left sides were compared in treated groups (G1 and G2) or between the right side of the treated group and untreated groups (G3 and G4). There was no difference between the group receiving 30 ultrasound applications and that receiving 45 applications. Morphometry revealed that, in comparison with their controls, the groups treated with both 30 and 45 ultrasound applications showed differences only in the tibia. The epiphyseal plate width was larger at all three study time points. The Proliferative zone was increased at week 13 only, and the Hypertrophic zone at weeks 13 and 26. In this study, ultrasound therapy caused no change in the longitudinal growth... (Complete abstract click electronic access below) / Doutor

Made available in DSpace on 2014-06-11T19:30:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-10-02Bitstream added on 2014-06-13T19:00:25Z : No. of bitstreams: 1 barreto_ac_dr_botfm.pdf: 1430672 bytes, checksum: 50ed11e9ab9e0afc2cb8922a3fb362fe (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O propósito deste estudo é determinar os efeitos do ultra-som terapêutico em baixa potência sobre a disco epifisial e o crescimento ósseo distal do fêmur e proximal da tíbia, em ratos jovens. Ratus Norvegicus com quatro semanas de vida, machos, totalizando 105 animais, foram submetidos à terapêutica de ultra-som (1,0 MHz, potência de 0,4 watt/cm2, cabeçote fixo, pulso contínuo, 10 minutos de duração, três ou quatro vezes por semana), na face medial do joelho direito. Um grupo de animais foi submetido a 30 aplicações de ultra-som, até a 13ª semana de vida e, outro a 45 aplicações, até a 18ª semana de vida. Os animais foram acompanhados até os seis meses. Foram estudadas as medidas do comprimento do fêmur e da tíbia e da largura das epífises distal do fêmur e proximal da tíbia e, a morfometria da altura do disco epifisial, como um todo e, de suas zonas histológicas. Os dados foram submetidos à análise de variância – fatorial inteiramente aleatorizado no nível de significância de 5%. Não foram encontradas diferenças significativas no crescimento ósseo longitudinal ou das larguras das epífises quando comparados lados direito e esquerdo nos grupos tratados (G1 e G2) e lado direito dos grupos tratados em relação ao respectivo controle (G3 e G4). Não houve diferença quando comparados os grupos tratados com 30 aplicações e 45 aplicações de ultra-som. A morfometria mostrou diferenças, somente na tíbia, em que tratado foi maior que controle, tanto para 30 quanto para 45 aplicações de ultra-som. Tratado foi maior do que controle, no disco epifisial, nos três momentos estudados; na zona de proliferação, somente na 13ª semana; e, na zona hipertrófica na 18ª e 26ª semanas. O ultra-som terapêutico, nas condições deste trabalho, não provocou alterações do comprimento... / The purpose of this study was to determining the effects of lowpower ultrasound therapy on the epiphyseal plate and the bone growth of the distal femur and the proximal tibia in young rats. One hundred five of four-week-old Rattus norvegicus males received ultrasound treatment of continuous therapeutic dose (1.0 MHz frequency, 0.4 watt/cm2, fixed probe, 10 minutes three or four times a week) on the medial face of the right knee. One group of animals underwent 30 ultrasound applications until the age of 13 weeks, and the other received 45 applications until the age of 18 weeks. The animals were followed up until they were six month old (26 weeks). Assessment included the measurement of the length of the femur and the tibia, the width of the femoral distal epiphysis and the proximal tibial epiphysis, and the morphometry of the reserve plus proliferative (Proliferative) and hypertrophic plus calcified hypertrophic (Hipertrophic) zones, as well as width of the epiphyseal plate. Totallyrandomized factorial variance analysis of the data was performed with significance level set at 5%. No significant differences were observed in longitudinal bone growth or epiphyseal width when right and left sides were compared in treated groups (G1 and G2) or between the right side of the treated group and untreated groups (G3 and G4). There was no difference between the group receiving 30 ultrasound applications and that receiving 45 applications. Morphometry revealed that, in comparison with their controls, the groups treated with both 30 and 45 ultrasound applications showed differences only in the tibia. The epiphyseal plate width was larger at all three study time points. The Proliferative zone was increased at week 13 only, and the Hypertrophic zone at weeks 13 and 26. In this study, ultrasound therapy caused no change in the longitudinal growth... (Complete abstract click electronic access below)

Este trabalho teve como objetivo realizar a investigação clínica dos efeitos do ultra-som de baixa intensidade como tratamento adjuvante na consolidação óssea de fraturas de ossos longos (rádio e ulna, fêmur, tíbia e fíbula) em cães. Foram utilizados 29 cães de raças variadas, 17 fêmeas e 12 machos, com faixa etária entre seis e 72 meses, 2,3 a 43 kg de peso corporal, portadores de fraturas recentes em ossos longos (rádio e ulna, fêmur, tíbia e fíbula), submetidos a procedimentos de osteossíntese (pinos intramedulares, fixação esquelética externa ou a associação destes métodos) e provenientes da rotina hospitalar de três instituições. Um dos cães apresentou fratura bilateral de tíbia e fíbula, tendo sido consideradas 30 fraturas. Os animais foram divididos em três grupos, de acordo com o local da fratura: GI (rádio e ulna), GII (fêmur), e GIII (tíbia e fíbula). Realizou-se o tratamento adjuvante de fraturas com ultra-som pulsado de baixa intensidade (30 mW/cm2 , durante 20 minutos, por 21 dias consecutivos) em 12 cães e 17 animais foram utilizados como controle. Todos os pacientes foram avaliados por exames clínicos e radiográficos nos períodos pré-operatório, pós-operatório imediato e aos 30 e 60 dias posteriores ao procedimento cirúrgico. Nos exames radiográficos foram observadas características de consolidação óssea, incluindo a presença ou ausência de reação periostal, ponte cortical, linha de fratura e formação de calo ósseo. O teste estatístico não paramétrico bilateral de Mann-Whitney foi empregado para a análise dos resultados dos achados radiográficos constatados nos animais dos grupos controle e tratado, não tendo sido verificadas diferenças significativas entre eles. Apesar da ausência de comprovação estatística, a maioria das fraturas tratadas com estimulação ultra-sônica demonstrou sinais clínicos e radiográficos de evolução favorável ao processo de consolidação óssea. Conforme os resultados observados neste estudo, o ultra-som pulsado de baixa intensidade pode ser indicado como tratamento adjuvante de fraturas recentes de ossos longos (rádio e ulna, fêmur, tíbia e fíbula), em animais da espécie canina. / This research had the purpose of investigating the clinical effects of low-intensity ultrasound on the healing of long bone fractures (radius and ulna, femur, tibia and fibula) in dogs. Twenty-nine dogs of different breeds were included in this study, being 17 females and 12 males, with ages ranging from six to 72 months, and weight from 2.3 to 43 kg. These animals presented a clinical history of recent long bone fractures (radius and ulna, femur, tibia and fibula), and underwent osteosynthesis procedures (intramedullary pins, external skeletal fixation or the association of both). All of the animals originated from three different veterinary hospitals. One of the dogs presented bilateral tibial fracture, encompassing a total of 30 fractures in such group. The animals were divided into three groups, according to the fracture site: GI; (radius and ulna), GII (femur), and GIII (tibia and fibula). The treatment with pulsed low-intensity ultrasound (30 mW/cm2 , for 20 minutes, for 21 consecutive days) was performed on 12 dogs, using 17 animals as a control group. All patients were evaluated through physical and radiographic examination before surgery, immediately on the postoperative, and after 30 and 60 days from the osteosynthesis. Postoperative and follow-up radiographs were examined for periosteal reaction, cortical bridging, fracture line and callus. The non-parametric bilateral Mann-Whitney Test was used to investigate the radiographic findings in the group undergoing treatment and in the control group. There were no significant statistical differences between them. In spite of these statistical results, most of the fractures treated with pulsed low-intensity ultrasound showed clinical and radiographic signs of bone healing in progress. According to these results, pulsed low-intensity ultrasound can be indicated as an adjunctive treatment for recent long bone fractures (radius and ulna, femur, tibia and fibula) in dogs.

Articular cartilage is a complex soft tissue covering the end of moving bones in joints which provide pressure load distribution over the joint surface and smooth lubrication with little friction for establishing movement. Articular cartilage has an intrinsically limited capacity for self-repair when injured due to the lack of nerve and blood supply. Considered that injured cartilage is left untreated, it is likely to undergo progressive cartilage degeneration without pain which may lead to posttraumatic osteoarthritis. Therefore functional and physiologic restoration of injured cartilage back to a normal condition has long been in demand, yet current available repairing methods in clinics have met with limited success. Mechanically applied loads to articular cartilage is necessary for chondrocytes, cartilage cells, since they are responsible for cartilage matrix turnover by synthesizing extracellular matrix (ECM) molecules in response to bio- chemical and mechanical changes in ECM. Ultrasound has emerged as an anabolic stimulator over the past few decades and a number of studies have proven that ultrasound therapy is beneficial for cartilage repair by synthesizing cartilage ECM components such as type II collagen and proteoglycan. Ultrasound therapy has also proven its potential for the attenuation of progressive cartilage degradation and induction of chondrogenic differentiation of mesenchymal stem cells. The use of ultrasound as an anabolic stimulator would be valuable with respect to cartilage repair since ultrasound as a form of mechanical energy can be non-invasively transferred into a human body. However, understanding the underlying mechanisms has been slow and the mechanisms have been roughly classified into thermal and non-thermal effects. Biologically detailed underlying mechanisms have not been sufficiently studied. That might be the reason why the application of ultrasound as a therapeutic tool has been limitedly available in clinics. In this study, mechanism involved biophysical effects of low intensity ultrasound has been studied for cartilage regeneration. First of all, the effect of ultrasound therapy as a mechanical stimulator on chondrogenic progenitor cell homing toward injured sites in cartilage was investigated with underlying biologic mechanisms. And the feasibility of ultrasound therapy for reactive oxygen species production mediated cartilage energy modulation was evaluated. There have been extensive preclinical studies about the effects of microbubble mediated ultrasound therapy on the targeted drugs or gene delivery into tissues of interest. Mechanical shock waves are released during ultrasound mediated microbubble destruction and the waves facilitate drug delivery into target tissues through transient blood vessel disruption. However, the clinical use of this technique has been limited through vascular system. In this study, the effects of microbubble mediated low intensity ultrasound therapy on directly delivered mechanical shock waves and controlled drug release were investigated. In conclusion, low intensity ultrasound therapy accelerates the homing of chondrogeic progenitor cells toward injured sites in cartilage via triggering mechanotransductive cell signaling pathways. This may result in speed up the return to normal cellularity and cartilage integrity by accelerating cartilage matrix repair. Low intensity ultrasound therapy was investigated as an energy modulator for chondrocytes via reactive oxygen species production in articular cartilage; however, little effects of ultrasound therapy driven cartilage energy modulation were found. The strong relationship between microbubbles mediated low intensity ultrasound therapy and the controlled release of drugs and mechanical shock waves was found. This strongly suggests that low intensity ultrasound therapy can play a role as a non-invasive controller for the release of drugs and lethal shock waves upon request.

Prostate cancer is the most prevalent cancer and the third-leading cause of cancer-related death among men in the developed world, with the number of cases expected to double within the next 15 years. Conventional therapies offer good control of local disease but are associated with high complication rates reducing long-term health-related quality-of-life significantly. MRI-guided transurethral ultrasound therapy has emerged as an attractive, minimally-invasive alternative for the treatment of localized prostate cancer, where the entire gland is heated to temperatures sufficient to cause irreversible thermal coagulation. A device inserted in the urethra uses multiple ultrasound transducers to produce directional heating patterns directly in the prostate. Adjusting the ultrasound power, frequency and device rotation rate enables high spatial control of the thermal lesion. MRI provides information essential to the accurate targeting of the prostate; anatomical images for device positioning and treatment planning, and quantitative temperature measurements within the prostate to compensate for dynamic tissue changes, using feedback control. This thesis develops a complete treatment delivery strategy for producing conformal regions of thermal coagulation shaped to whole-gland prostate volumes, while limiting the thermal impact to the surrounding important anatomy. First, acoustic and thermal simulations incorporating a novel temperature feedback controller were used to model and shape regions of coagulation to human prostate geometries with a high degree of accuracy. Second, treatment delivery strategies were developed and simulated to reduce thermal injury to the surrounding anatomy, below the threshold for sustained damage. Third, experiments in tissue-mimicking gel phantoms confirmed the predictive accuracy of the simulations and the feasibility of producing conformal volumes of coagulation using transurethral ultrasound devices and MRI-temperature feedback. This work forms the basis of clinical treatment delivery methods and supports the use of the simulations as a planning tool to enhance the inherent compromise between safety and efficacy on a patient-specific basis.

Prostate cancer is the most prevalent cancer and the third-leading cause of cancer-related death among men in the developed world, with the number of cases expected to double within the next 15 years. Conventional therapies offer good control of local disease but are associated with high complication rates reducing long-term health-related quality-of-life significantly. MRI-guided transurethral ultrasound therapy has emerged as an attractive, minimally-invasive alternative for the treatment of localized prostate cancer, where the entire gland is heated to temperatures sufficient to cause irreversible thermal coagulation. A device inserted in the urethra uses multiple ultrasound transducers to produce directional heating patterns directly in the prostate. Adjusting the ultrasound power, frequency and device rotation rate enables high spatial control of the thermal lesion. MRI provides information essential to the accurate targeting of the prostate; anatomical images for device positioning and treatment planning, and quantitative temperature measurements within the prostate to compensate for dynamic tissue changes, using feedback control. This thesis develops a complete treatment delivery strategy for producing conformal regions of thermal coagulation shaped to whole-gland prostate volumes, while limiting the thermal impact to the surrounding important anatomy. First, acoustic and thermal simulations incorporating a novel temperature feedback controller were used to model and shape regions of coagulation to human prostate geometries with a high degree of accuracy. Second, treatment delivery strategies were developed and simulated to reduce thermal injury to the surrounding anatomy, below the threshold for sustained damage. Third, experiments in tissue-mimicking gel phantoms confirmed the predictive accuracy of the simulations and the feasibility of producing conformal volumes of coagulation using transurethral ultrasound devices and MRI-temperature feedback. This work forms the basis of clinical treatment delivery methods and supports the use of the simulations as a planning tool to enhance the inherent compromise between safety and efficacy on a patient-specific basis.