Intravascular ultrasound catheter to enhance microbubble-based drug delivery via acoustic radiation force

• Published in: IEEE transactions on ultrasonics, ferroelectrics, and frequency control ferroelectrics, and frequency control, 2012-10, Vol.59 (10), p.2156-2166
• Main Authors: Kilroy, J. P., Klibanov, A. L., Wamhoff, B. R., Hossack, J. A.
• Format: Article
• Language: English
• Subjects: Acoustic signal processing; Acoustics; Biological and medical sciences; Cardiovascular system; Carotid Arteries - diagnostic imaging; Catheters; Contrast Media - chemistry; Contrast Media - pharmacokinetics; Drug Delivery Systems - instrumentation; Drug Delivery Systems - methods; Exact sciences and technology; Finite Element Analysis; Force; Fundamental areas of phenomenology (including applications); Humans; Imaging; Investigative techniques, diagnostic techniques (general aspects); Medical research; Medical sciences; Microbubbles; Models, Cardiovascular; Phantoms, Imaging; Physics; Prototypes; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Technology. Biomaterials. Equipments. Material. Instrumentation; Transducers; Ultrasonic imaging; Ultrasonic investigative techniques; Ultrasonography, Interventional - instrumentation; Ultrasonography, Interventional - methods
• ISSN: 0885-3010; 1525-8955
• DOI: 10.1109/TUFFC.2012.2442

Previous research has demonstrated that acoustic radiation force enhances intravascular microbubble adhesion to blood vessels in the presence of flow for molecular-targeted ultrasound imaging and drug delivery. A prototype acoustic radiation force intravascular ultrasound (ARFIVUS) catheter was designed and fabricated to displace a microbubble contrast agent in flow representative of conditions encountered in the human carotid artery. The prototype ARFIVUS transducer was designed to match the resonance frequency of 1.4- to 2.6-μm-diameter microbubbles modeled by an experimentally verified 1-D microbubble acoustic radiation force translation model. The transducer element was an elongated Navy Type I (hard) lead zirconate titanate (PZT) ceramic designed to operate at 3 MHz. Fabricated devices operated with center frequencies of 3.3 and 3.6 MHz with -6-dB fractional bandwidths of 55% and 50%, respectively. Microbubble translation velocities as high as 0.86 m/s were measured using a high-speed streak camera when insonating with the ARFIVUS transducer. Finally, the prototype was used to displace microbubbles in a flow phantom while imaging with a commercial 45-MHz imaging IVUS transducer. A sustained increase of 31 dB in average video intensity was measured following insonation with the ARFIVUS, indicating microbubble accumulation resulting from the application of acoustic radiation force.