5A-1 Multi-frequency Array Development for Drug Delivery Therapies: Characterization and First Use of a Triple Row Ultrasound Probe

Ultrasound-mediated drug delivery involves the application of acoustic energy to manipulate drug carrying vehicles in the microvasculature. The therapeutic goal is a site-targeted delivery of a specific drug carried by microscopic vehicles directed by the presence of ultrasonic beam energy. In sequentially-activated modes the acoustic beam can be controlled to both push the vehicles in small blood vessels and then also deploy their drug payload at specific application target sites. Effective ultrasound mediated drug delivery and microbubble imaging require broad band arrays that can both image the targeted region and deliver a therapeutic treatment. Two array designs have been built and tested to support drug delivery experiments. The first (the "Jupiter") is a single row phased array with each of 64 elements at 260 micron pitch. The elements in this array were made in a three piezoelectric layer stack for high power operation at 2.02 MHz and a 2-way fractional band width of 86%. Although not a "multi-frequency" array, its wide band performance has helped to contribute to initial experiments in the combination of imaging and acoustic delivery of significant low frequency (1 MHz) therapeutic pressures, with low frequency output intensity (Isppa) on the order of 150 W/cm 2 for long pulse durations. The second probe design, the "CoLinear1-6", is a novel integration of low and high frequency arrays, and is the principal subject of the results presented. The center row high frequency array is surrounded on each side with a low frequency array wired with 1.5D connectivity. The CoLinear1-6, as a multi-frequency array combination, integrates more effectively high quality imaging with the therapeutic utility of a low frequency array. In this linear multi-row array construction, the center row is comprised 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 are made of 64 elements and are spaced at 1.67 lambda pitch operating at 1.48 MHz with a -6 dB (2-way) fractional bandwidth >50%. Beam performance was measured to assure optimal overlap at the 2 to 5 cm depth range. An array thermal model was constructed to provide a predictive internal temperature during experiments involving therapeutic protocols