I. Simiantonakis

Quantitative MR temperature monitoring of high-intensity focused ultrasound therapy.

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.

Control of cavitation activity by different shockwave pulsing regimes.

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.

CT on-line monitoring of HIFU therapy

It was the aim of this study to evaluate the feasibility of a clinical CT scanner for temperature mapping in high intensity focused ultrasound tumor therapy. The authors used a 1.2 MHz ultrasound transducer for HIFU on fresh pig muscle. Image acquisition was performed with a clinical CT Scanner before, during and after HIFU. They were able to determine the spatial and temporal temperature development during HIFU application as hypodense zones in the performed images. Thermal necroses were shown as hyperdense areas in the CT images. Moreover, the authors were able to detect bubble formation due to vaporization during US application. Calibration showed a CT thermosensitivity of -0.43 HU//spl deg/C in pig muscle tissue.

MR monitoring of focused ultrasound surgery in a breast tissue model in vivo

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.

Kernspingesteuerte Therapie mit fokussiertem Ultraschall: Nichtinvasive Chirurgie des Mammakarzinoms?

ZusammenfassungDie magnetresonanzgesteuerte fokussierte Ultraschallchirurgie (MRgFUS: Magnet Resonance guided Focused Ultrasound Surgery) hat das Potenzial, eine relevante Therapiemodalität in der adjuvanten, neoadjuvanten oder auch palliativen onkologischen Situation zu werden. Mögliche klinische Ziele sind ultraschallzugängliche Weichteiltumoren. Wegen ihrer exponierten und wenig atemverschieblichen Lage zählen hierzu insbesondere Tumoren der Mamma.Fokussierter Ultraschall ist physikalisch gesehen das einzige Verfahren, mit dem echte nichtinvasive Chirurgie unter gleichzeitigem kernspintomographischen Temperaturmonitoring realisiert werden kann. Nach einer Einstrahlzeit von wenigen Sekunden entsteht im Schallfokus lokal eine so hohe Temperatur (60–85°C), dass das Tumorgewebe umgehend nekrotisiert werden kann.In der vorliegenden Arbeit stellen wir die in Heidelberg erfolgte Entwicklung und den Aufbau einer klinisch an einem 1,5-T-Ganzkörper-MR-Tomographen einsetzbare Ultraschalltherapieeinheit sowie deren Transfer vom physikalischen Experiment bis zum klinischen Einsatz dar. Wir zeigen damit durchgeführte Experimente an verschieden Phantomen und Ex-vivo-Geweben und demonstrieren In-vivo-Experimente an der Mamma von Schafen als Modell für die menschliche Mamma. Ausgehend von den erfolgreichen Tierstudien berichten wir über die Therapie an der humanen Mamma bis hin zum ersten erfolgreichen Einsatz der MRgFUS beim Mammakarzinom am Menschen in Heidelberg. Über die klinische Rolle dieses neuen, nichtinvasiven, interventionellen radiologischen Therapieverfahrens müssen nun klinische Studien entscheiden.AbstractMagnetic 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°C to 85°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.

Treatment acceleration by modification of sound fields and sonication modalities

High intensity focused ultrasound can produce a small tissue necrosis deeply inside the body. By setting several of these lesions next to each other a larger volume, e.g. a tumor, can be coagulated non-invasively. Normally the tumor which has to be treated has a volume of several cm/sup 3/, whereas a single ultrasound lesion typically has only a volume of a few mm/sup 3/. Therefore, a lot of single ultrasound shots are needed to treat the whole tumor, resulting in a long treatment time. In this study several approaches were investigated to reduce the time. Therefore we have investigated several methods: lenses, a different sonication order and ultrasound exposure during transducer movement. We achieved results comparable to the normal treatment, while the treatment time was reduced by a factor of more than eight.

MRI guided focused ultrasound surgery for the treatment of breast cancer

HIFU is an effective tool to generate precise localized tissue heating and subsequent tissue necroses deep in the body. Especially in combination with MRI target definition, detection of the heated area and the detection of morphological tissue changes are possible. After previous animal trials we show in the present study the transfer of this method to the clinical application. We have treated human breast cancer with HIFU under MRI guidance. For this purpose, a clinical treatment unit was developed and built up. A prospective clinical phase I study was started involving patients with biopsy proven invasive breast cancer. MRI-guided focused ultrasound therapy was applied before conventional breast surgery. On MR-images breast tumor delineation, tumor segmentation and HIFU treatment planning was possible. During ultrasound therapy, detection of the thermal focus and comparison with the planned focus position allowed a quasi on-line therapy control. Immediately after ultrasound therapy affected areas could be distinguished after intravenous application of MRI contrast agent as non-perfused area. Thus we could demonstrate that breast cancer in a human patient can be treated non-invasively in a single therapy session with HIFU under MRI guidance.

ESR dosimetry of free radicals-a comparison between high intensity ultrasound fields and an ionizing Cs/sup 137/ source

High intensity ultrasound fields have the potential to produce free radicals in aqueous solutions caused by inertial cavitation. In this study we compared the production of free radicals under different sonication modalities with radical formation in the field of a well known Cs/sup 137/ gamma-ray source. In addition we examined the enhancement of radical production by photodynamic substances. Analysis of radical formation was performed with an ESR spectrometer. Sonication of aqueous test solution was carried out with high intensity focused ultrasound (HIFU) and with an unfocused ultrasound field in a standing wave mode against a solution/air interface. We were able to assess the quantity of free radicals developing in photon field as well as in US fields. It was feasible to determine equivalent dose values comparing ultrasound with photon irradiation. A significant enhancement of radical production by a photosensitizer was only detected in the unfocused ultrasound field in a standing wave mode.