ABSTRACT
Focused ultrasound phased array systems have attracted increased attention for brain therapy applications. However, such systems currently lack a direct and real-time method to intraoperatively monitor ultrasound pressure distribution for securing treatment. This study proposes a dual-mode ultrasound phased array system design to support transmit/receive operations for concurrent ultrasound exposure and backscattered focal beam reconstruction through a spherically focused ultrasound array. A 256-channel ultrasound transmission system was used to transmit focused ultrasonic energy (full 256 channels), with an extended implementation of multiple-channel receiving function (up to 64 channels) using the same 256-channel ultrasound array. A coherent backscatter-received beam formation algorithm was implemented to map the point spread function (PSF) and focal beam distribution under a free-field/transcranial environment setup, with the backscattering generated from a strong scatterer (a point reflector or a microbubble-perfused tube) or a weakly scattered tissue-mimicking graphite phantom. Our results showed that PSF and focal beam can be successfully reconstructed and visualized in free-field conditions and can also be transcranially reconstructed following skull-induced aberration correction. In vivo experiments were conducted to demonstrate its capability to preoperatively and semiquantitatively map a focal beam to guide blood-brain barrier opening. The proposed system may have potential for real-time guidance of ultrasound brain intervention, and may facilitate the design of a dual-mode ultrasound phased array for brain therapeutic applications.
Subject(s)
Brain/diagnostic imaging , Ultrasonic Therapy , Ultrasonography , Algorithms , Animals , Blood-Brain Barrier/diagnostic imaging , Equipment Design , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Microbubbles , Phantoms, Imaging , Rats , Skull/diagnostic imaging , Ultrasonic Therapy/instrumentation , Ultrasonic Therapy/methods , Ultrasonography/instrumentation , Ultrasonography/methodsABSTRACT
Focused ultrasound (FUS) in the presence of microbubbles can bring about transcranial and local opening of the blood-brain barrier (BBB) for potential noninvasive delivery of drugs to the brain. A phased-array ultrasound system is essential for FUS-BBB opening to enable electronic steering and correction of the focal beam which is distorted by cranial bone. Here, we demonstrate our prototype design of a 256-channel ultrasound phased-array system for large-region transcranial BBB opening in the brains of large animals. One of the unique features of this system is the capability of generating concurrent dual-frequency ultrasound signals from the driving system for potential enhancement of BBB opening. A wide range of signal frequencies can be generated (frequency = 0.2-1.2 MHz) with controllable driving burst patterns. Precise output power can be controlled for individual channels via 8-bit duty-cycle control of transistor-transistor logic signals and the 8-bit microcontroller-controlled buck converter power supply output voltage. The prototype system was found to be in compliance with the electromagnetic compatibility standard. Moreover, large animal experiments confirmed the phase switching effectiveness of this system, and induction of either a precise spot or large region of BBB opening through fast focal-beam switching. We also demonstrated the capability of dual-frequency exposure to potentially enhance the BBB-opening effect. This study contributes to the design of ultrasound phased arrays for future clinical applications, and provides a new direction toward optimizing FUS brain drug delivery.
Subject(s)
Drug Delivery Systems/methods , Ultrasonography, Interventional/methods , Animals , Blood-Brain Barrier/diagnostic imaging , Echoencephalography , Equipment Design , Humans , Skull/diagnostic imaging , Swine , Ultrasonography, Interventional/instrumentationABSTRACT
Discrepancies between hyperecho-predicted necrosed volume in ultrasound (US) images and the actual size of a thermal lesion might cause incomplete ablation or damage normal structures during high intensity focused US (HIFU) ablations. A novel dual-frequency sonication procedure is proposed to reduce this discrepancy. HIFU transducers of either 1 or 3.5 MHz were applied to transparent tissue-mimicking phantoms and ex vivo bovine liver samples. A diagnostic probe and a charge-coupled device (CCD) camera were used to record lesion formation in real time, allowing for comparison of the sizes of the hyperechoes in US images and the protein denaturing area on optical images. Bovine liver specimens were segmented to reveal the lesion's terminal sizes. Differences between actual lesion volume and hyperechoes in US images were demonstrated to be dependent on acoustic frequency and intensity. At a low frequency (1 MHz), the hyperechoes appeared to be larger than the actual volume, but the difference decreased with the duration of ablation. In contrast, at a high frequency (3.5 MHz), the hyperechoes were smaller for ablations lasting longer than 10 s. Moreover, given certain low-intensity conditions, lesions were formed without detectable hyperechoes (3.5 MHz), or hyperechoes appeared before a visible lesion was formed (1 MHz). Dual frequency sonications (low frequency followed by high frequency) produce more stable and larger lesions, and with less position shift, which might be useful for designing future ablation strategies.
