Dual-frequency Transducers for Ultrasound Imaging and Therapy
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Chemotherapy is a widely used treatment option for managing cancer disease. It is a systemically administered treatment, meaning that when applied, it affects the whole body. Only a small fraction of the drug reaches the primary tumour. Research is being conducted on how to increase this fraction by using drugs encapsulated in various drug carriers. The drug carriers are more easily trapped in the tumour than in healthy tissue. Ultrasound is being studied as a method to release the drug from the drug carriers in a specific location, i.e. the tumour. To do this with ultrasound, the tumour must first be located. One method for locating tumours is to use micro-bubbles, which are systemically injected and also accumulate in the tumour, if the tumour is well perfused. Dual-frequency ultrasound can detect micro-bubbles at frequencies above the bubble resonance, yielding higher image resolution. The drug carriers may be connected to the micro-bubbles, which means ultrasound can indirectly detect the presence of encapsulated drugs in the tumour. The drug may be released by ultrasound after it is detected. However, after being released, the drug remains trapped close to the blood vessels in the tumour, which limits the efficacy of the treatment. There is a need to push either the drug carriers or the drugs themselves deeper into the tumour. In summary, ultrasound needs to detect micro bubbles with or without attached drug carriers, release the drugs in a specified location, and facilitate deeper penetration of drugs into the tumour tissue. This work focuses on how to design dual-frequency ultrasound transducers that can handle all of these tasks. The transducer design is analysed by mathematical analysis, and simulations of acoustics and heating. In order to gain some insight into what ultrasound parameters are required to facilitate drug penetration into tumours, an animal experiment is conducted. The results of the experiment are compared with acoustic simulations of the physical situation. It is found that the dual-frequency design can be made more flexible in terms of which frequencies can be produced by the transducers. A new design concept is proposed in which the ratio between the high and low frequency in the transducer can be varied arbitrarily above ∼6:1. It is also proven that ultrasound can be used to push drug carrying agents deeper into tumour tissues, though the physics of the process is not fully understood. The effect is produced with an ultrasound intensity of 7.72Wcm−2 in the focus of the transducer, with a transmit frequency of 10 MHz. It is also found that the proposed design concept for dual-frequency transducers can be utilised for cooling of the transducer. The new design increases the amount of power that can be transmitted by the transducer without exceeding ultrasound safety limits by up to a factor of ten. The new design of the dual-frequency transducer can improve the detection of micro-bubbles and the suppression of reverberation noise in ultrasound images. The animal experiment shows that ultrasound may play yet another significant role in improving the efficacy of chemotherapy in solid tumours. The improved thermal properties of the dual-frequency transducer implies that it can be used for such treatment, while at the same time improving image quality and micro-bubble detection.