Three-Dimensional Transcranial Ultrasound Imaging of Microbubble Clouds Using a Sparse Hemispherical Array

Abstract

There is an increasing interest in bubble-mediated focused ultrasound (FUS) interventions in the brain. However, current technology lacks the ability to spatially monitor the interaction of the microbubbles with the applied acoustic field, something which is critical for safe clinical translation of these treatments. Passive acoustic mapping could offer a means for spatially monitoring microbubble emissions that relate to bubble activity and associated bioeffects. In this study a hemispherical receiver array was integrated within an existing transcranial therapy array to create a device capable of both delivering therapy and monitoring the process via passive imaging of bubble clouds. A 128-element receiver array was constructed and characterized for varying bubble concentrations and source spacings. Initial in vivo feasibility testing was performed. The system was found to be capable of monitoring bubble emissions down to single bubble events through an ex vivo human skull. The lateral resolution of the system was found to be between 1.25-2 mm and the axial resolution between 2-3.5 mm, comparable to the resolution of MRI-based temperature monitoring during thermal FUS treatments in the brain. The results of initial in vivo experiments show that bubble activity can be mapped starting at pressure levels below the threshold for Blood-Brain barrier disruption. This study presents a feasible solution for imaging bubble activity during cavitation-mediated FUS treatments in the brain.

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

“…61,66,74 Briefly, the transmit array consisted of a subset of 128 elements from a 30 cm diameter, hemispherical phased array comprising 1372, 10 mm diameter piezoceramic tube elements with a fundamental frequency of 306 kHz. 74 The receive array consisted of 128, 2.5 mm diameter piezoceramic disk elements operating at a center frequency of 612 kHz, tuned to the second harmonic of the transmit array.…”

“…74 The receive array consisted of 128, 2.5 mm diameter piezoceramic disk elements operating at a center frequency of 612 kHz, tuned to the second harmonic of the transmit array. 61,66 The receiver elements were fixed in the middle of 128 transmit elements in a sparse, pseudorandomized arrangement [ Fig. 1(a)] that was optimized to suppress grating lobe formation and improve image quality through computer simulations.…”

“…However, the information obtained from a single-element PCD is fundamentally limited due to the inherent trade-off between the volume of sensitivity and spatial specificity of the device. The use of multielement arrays, combined with passive beamforming algorithms borrowed from other fields, [45][46][47][48] has been shown to overcome this limitation and enable spatial mapping of cavitation activity during the application of FUS in both in vitro [49][50][51][52][53][54][55][56][57][58][59][60][61][62] and in vivo [63][64][65][66][67] settings. The integration of passive imaging during mechanicalbased FUS brain therapies would make the procedures practical, by providing a method for real-time treatment monitoring and control.…”

“…74 We have previously characterized the receiver array and demonstrated our system's ability to image bubble clouds transcranially during ultrasound brain therapy 66 through the use of an invasive, source-based skull correction method. [75][76][77] In a separate study, we demonstrated that computed tomography (CT)-based aberration corrections, 78,79 currently used in clinical FUS brain treatments 78 for precise focusing of the therapy beam, 2,5 can additionally be used during beamforming on receive to spatially map acoustic source fields through a human skull in silico.…”

Closed-loop control of targeted ultrasound drug delivery across the blood–brain/tumor barriers in a rat glioma model

“…Moreover, we only recorded with a single channel, and data from all emission signals in the active field of receiver were used by the controller. However, passive cavitation imaging (PCI) has been recently realized for brain applications (42,43). Combining PCI into our control system may offer vital spatial information of cavitation activities and prevent cavitation from happening in undesired regions (for example, the damage area shown in Fig.…”