Dual-Mode 1-D Linear Ultrasound Array for Image-Guided Drug Delivery Enhancement Without Ultrasound Contrast Agents.

Abstract

Pulsed high-intensity focused ultrasound (pHIFU) uses nonlinearly distorted millisecond-long ultrasound pulses of moderate intensity to induce inertial cavitation in tissue without administration of contrast agents. The resulting mechanical disruption permeabilizes the tissue and enhances the diffusion of systemically administered drugs. This is especially beneficial for tissues with poor perfusion such as pancreatic tumors. Here, we characterize the performance of a dual-mode ultrasound array designed for image-guided pHIFU therapies in producing inertial cavitation and ultrasound imaging. The 64-element linear array (1.071 MHz, an aperture of 14.8×51.2 mm, and a pitch of 0.8 mm) with an elevational focal length of 50 mm was driven by the Verasonics V-1 ultrasound system with extended burst option. The attainable focal pressures and electronic steering range in linear and nonlinear operating regimes (relevant to pHIFU treatments) were characterized through hydrophone measurements, acoustic holography, and numerical simulations. The steering range at ±10% from the nominal focal pressure was found to be ±6 mm axially and ±11 mm azimuthally. Focal waveforms with shock fronts of up to 45 MPa and peak negative pressures up to 9 MPa were achieved at focusing distances of 38-75 mm from the array. Cavitation behaviors induced by isolated 1-ms pHIFU pulses in optically transparent agarose gel phantoms were observed by high-speed photography across a range of excitation amplitudes and focal distances. For all focusing configurations, the appearance of sparse, stationary cavitation bubbles occurred at the same P- threshold of 2 MPa. As the output level increased, a qualitative change in cavitation behavior occurred, to pairs and sets of proliferating bubbles. The pressure P- at which this transition was observed corresponded to substantial nonlinear distortion and shock formation in the focal region and was thus dependent on the focal distance of the beam ranging within 3-4 MPa for azimuthal F -numbers of 0.74-1.5. The array was capable of B-mode imaging at 1.5 MHz of centimeter-sized targets in phantoms and in vivo pig tissues at depths of 3-7 cm, relevant to pHIFU applications in abdominal targets.