3B-2 Efficient Array Design for Sonotherapy Enhanced Drug Delivery

Activated delivery of drug-encapsulated vehicles to target sites in the body can be implemented with the use of drug- carrying thermally-sensitive liposomes which can release their contents at specifically identified sites. We have designed an array to initiate a site-targeted liposome drug release through a controlled local rise in tissue temperature by a few degrees. A high performance multi-row array which can simultaneously both image and treat a tumor site has been proposed; here we describe the use of this array for thermal treatment. In this application, the heat is supplied by an efficient ultrasound array to release the liposome carrying drug payload directly to the tumor site. A multi-frequency compound array has been constructed and tested in a linear multi-row array construction. The high performance imaging center row is made of 128 elements at 1.1 lambda pitch operating at 5.24 MHz with a -6 dB fractional bandwidth of 73%; the two outer rows, one on each side of the center row and hard wired together in a 1.5D format, are made of 64 elements each. The two outer rows in the initial design operate at 1.48 MHz and a -6 dB fractional bandwidth of 54% with a 0.67 lambda pitch. To operate the outer rows in a sonotherapy mode, the array, cable and probe electrical interface to the system were optimized to achieve high efficiency tissue heating. To select the most efficient narrow band transmit frequency, our KLM model was used to predict the best ratio of spectral estimates of the array effective electrical load resistances that determine the acoustic radiated power and dissipative losses. Thermal models were also used in various modes of operation to predict critical internal array temperatures where practical measurements are challenging. Delivery of 10 watts of average acoustic power is desired for relatively long periods, to be directed to a 1 square centimeter area at depths in the range of 20 to 50 mm in order to raise the tissue temperature by several degrees. The overall transmission efficiency of the original commercial high bandwidth imaging design is 20%, the new design is 40% efficient. Our KLM transmission model was used to predict a marked overall improvement of double this efficiency while using an unmodified Siemens Antares imaging system. The operational result is a probe-based improved efficiency acoustic power delivery system for sonotherapy enhanced targeted drug release that maintains internal array temperatures at less than 60C.