RESUMEN
There is an increasing interest in high intensity focused ultrasound (HIFU) for thermo ablative tumor therapy. The attractiveness of this method is based on its ability to destroy tumor tissue non invasively while sparing surrounding tissue from outside the body. HIFU induced tissue necroses are sharply circumscribed. Therefore this method was termed focused ultrasound surgery (FUS). The therapeutic potential of FUS is under investigation in several clinical studies. Main objects of these studies are prostate carcinomas, breast kidney and liver tumors. The next innovative step will be the non invasive FUS treatment of brain through the intact skull. Combining FUS with magnetic resonance imaging (MRI) or diagnostic ultrasound allows accurate and online therapy guiding and monitoring. This article gives an overview of the basics, the latest developments and actual clinical studies in the field of focused ultrasound surgery.
Asunto(s)
Electrocoagulación/instrumentación , Neoplasias/cirugía , Terapia por Ultrasonido/instrumentación , Diseño de Equipo/tendencias , Predicción , Humanos , Necrosis , Neoplasias/patología , Sistemas en Línea/instrumentación , Cirugía Asistida por Computador/instrumentación , TransductoresRESUMEN
An ideal vision of modern medicine includes tumor surgery with the human body remaining completely intact. A noninvasive therapy could avoid infections and scar formation; it would require less anesthesia, reduce recovery time, and possibly also reduce costs. This study investigated whether human breast cancer can be effectively treated with a novel combination of image guidance and energy delivery, noninvasive magnetic resonance imaging (MRI)-guided focused ultrasound (FUS). We have developed a FUS therapy unit guided by MRI for the treatment of human breast tumors in a clinical 1.5 T MR scanner. With interactive target segmentation on MRI, defined volumes could be noninvasively treated in a single session with on-line MR temperature control. The ultrasound waves were focused through the intact skin and resulted in the localized thermal tissue ablation at a maximum temperature of 70 degrees C. The therapy principle was first demonstrated in sheep breast in vivo and was then applied in a patient with core biopsy-proven invasive breast cancer 5 days before breast-conserving surgery. MRI proved suitable to delineate the breast cancer, served as stereotactic treatment planning platform, and delineated the FUS-related tissue changes such as interruption of tumor blood flow. Furthermore, MRI localized the hot spot in the tumor and measured temperature elevation during the treatment. This allowed us to monitor the efficacy and safety of FUS therapy. Immunohistochemistry of the resected specimen demonstrated that FUS homogeneously induced lethal and sublethal tumor damage with consecutive up-regulation of p53 and loss of proliferative activity. This effect was realized without anesthesia and damage to the surrounding healthy tissue or systemic effects. Overall, our results show that noninvasive MRI-guided therapy of breast cancer is feasible and effective. Thus, MRI-guided FUS may represent a new strategy for the neoadjuvant, adjuvant, or palliative treatment in selected breast cancer patients and in patients with other soft-tissue tumors.
Asunto(s)
Neoplasias de la Mama/cirugía , Imagen por Resonancia Magnética/métodos , Neoplasias Mamarias Experimentales/cirugía , Animales , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/diagnóstico por imagen , Modelos Animales de Enfermedad , Femenino , Humanos , Neoplasias Mamarias Experimentales/irrigación sanguínea , Neoplasias Mamarias Experimentales/diagnóstico por imagen , Persona de Mediana Edad , Ovinos , UltrasonografíaRESUMEN
The objective of this study was to investigate MRI methods for monitoring focused ultrasound surgery (FUS) of breast tumors. To this end, the mammary glands of sheep were used as tissue model. The tissue was treated in vivo with numerous single sonications which covered extended target volumes by employing a scanning technique. The ultrasound focus position was controlled by online temperature mapping based on the temperature dependence of the relaxation time T(1). This approach proved to be reliable and offers thus an alternative to proton resonance frequency methods, whose application is hampered in fatty tissues. FUS-induced tissue changes were visible on T(2)- as well as on pre- and post-contrast T(1)-weighted images. According to our initial experience, noninvasive MRI-guided FUS of breast tumors is feasible.
Asunto(s)
Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/instrumentación , Glándulas Mamarias Animales/cirugía , Monitoreo Intraoperatorio/instrumentación , Terapia por Ultrasonido/instrumentación , Tejido Adiposo/cirugía , Animales , Temperatura Corporal/fisiología , Femenino , Glándulas Mamarias Animales/patología , OvinosRESUMEN
Magnetic resonance guided focused ultrasound surgery (MRgFUS) has the potential to become an important therapy modality in the adjuvant, neoadjuvant or palliative cancer treatment. All ultrasound accessible regions are possible target areas, especially breast tumors. Ultrasound propagation is well predictable. The ultrasound energy can be focused to a defined spot through the intact skin, and temperatures of 60 degrees C to 85 degrees C can be induced locally for a few seconds that instantaneously necrose biological tissues, while sparing surrounding healthy tissue. In addition, MRI is sensitive to temperature allowing for online monitoring of the temperature focus. In this work we demonstrate our Heidelberg experiments from basic research and animal studies towards the clinical realization of MRgFUS in breast cancer patients. The most important of these experiments involved sheep as an appropriate model for the human breast. A new therapy setup is designated to treat human breast patients in a clinical 1.5 T MRI scanner. While the therapies have been successful so far without any side effects, the future clinical role of noninvasive MRgFUS has to be defined by clinical studies.
Asunto(s)
Neoplasias de la Mama/terapia , Imagenología Tridimensional/instrumentación , Imagen por Resonancia Magnética/instrumentación , Terapia por Ultrasonido/instrumentación , Animales , Neoplasias de la Mama/diagnóstico , Terapia Combinada , Diseño de Equipo , Femenino , Fibroadenoma/diagnóstico , Fibroadenoma/terapia , Humanos , Conejos , Ratas , OvinosRESUMEN
The aim of the study was to control the number of inertial cavitation bubbles in the focal area of an electromagnetic lithotripter in water independently of peak intensity, averaged intensity or pressure waveform. To achieve this, the shockwave pulses were applied in double pulse sequences, which were administered at a fixed pulse repetition frequency (PRF) of 0.33 Hz. The two pulses of a double pulse were separated by a variable short pulse separation time (PST) ranging from 200 micros to 1500 ms. The number and size of the cavitation bubbles were monitored by scattered laser light and stroboscopic photographs. We found that the number of inertial cavitation bubbles as a measure of cavitation dose was substantially influenced by variation of the PST, while the pressure pulse waveform, averaged acoustic intensity and bubble size were kept constant. The second pulse of each double pulse generated more cavitation bubbles than the first. At 14 kV capacitor voltage, the total number of cavitation bubbles generated by the double pulses increased with shorter PST down to approximately 400 micros, the cavitation lifespan. The results can be explained by cavitation nuclei generated by the violently imploding inertial cavitation bubbles. This method of pulse administration and cavitation monitoring could be useful to establish a cavitation dose-effect relationship independently of other acoustic parameters.
Asunto(s)
Ondas de Choque de Alta Energía , Relación Dosis-Respuesta en la Radiación , Rayos Láser , Litotricia/métodos , Dispersión de Radiación , Factores de Tiempo , UltrasonidoRESUMEN
A new quantitative method has been developed for real-time mapping of temperature changes induced by high intensity focused ultrasound (HIFU). It is based on the temperature dependence of the T1 relaxation time and the equilibrium magnetization. To calibrate the temperature measurement, the functional relationship between T1 and temperature was examined in different samples of porcine muscle and fatty tissue. The method was validated by a comparison of calculated temperature maps with fiber-optic measurements in heated muscle tissue. The experiment showed that the accuracy of the MR method for temperature measurements is better than 1 degree C. Since the acquisition time of the employed MR sequence takes only 3 s per slice and the calculation of the temperature map can be performed within seconds, the imaging technique works nearly in real-time. The temperature measurement could be realized during HIFU showing no disturbances by ultrasound sonication. In comparison to other MR approaches, the advantages of the introduced method lie in a sufficient accuracy and time resolution combined with a reasonable robustness against motion as well as the feasibility for temperature monitoring in fatty tissues.