Characterization of Transcranial Focused Ultrasound Field to Reduce Ultrasonic Standing Waves

Background: The transcranial Focused Ultrasound (tFUS) is an emerging brain stimulation technique that is  able to modulate the brain circuits in a safe and reversible manner by focusing ultrasonic pressure waves at  an intracranial target location and transmit ultrasound energy through the skull and into the brain. While  tFUS as a non-invasive neuromodulation paradigm has many promising attributes such as high spatial  resolution, focality, and depth penetration, and has been shown to be able to modulate neuronal activity in a  variety of animal and human models, however, from the rodent model studies, concerns have been raised  regarding the origin of the tFUS-induced activity.  

Objective: In this study, we investigate the effect of standing wave formations inside the skull cavity of both  a rodent (Wistar rat) and a human model in affecting the specificity of the tFUS pressure waves in the entire  brain region with specific attention to the targeted location and introduce a method to eliminate these  intracranial standing waves.  

Method: In a series of simulation and ex-vivo experiments for both the rat and the human model, we first  examine the ultrasound pressure field distribution and characterize the intracranial standing waves that are  formed by tFUS when driven by the conventional ultrasound waveform. We then introduce a novel method  of driving the tFUS transducer that is designed to minimize the unintended transmission of ultrasound energy  inside the brain by reducing the formation of standing waves. We will also investigate our method in a set of  3 in-vivo rat subjects where we stimulate the primary somatosensory cortex and simultaneously record the  local field potential (LFP) at the targeted location as well as the primary auditory cortex to study the effect  of using a standing wave suppression method to reduce the confounding auditory activity.

Results: We first show that in the rodent model, extensive standing waves are present when using the field  standard waveform to drive the transducer deduced from both simulation and ex-vivo experiments. We then  verify that our introduced customized waveform is able to reduce these intracranial standing waves. Lastly,  for the larger skull size of the human model, we demonstrate that the standing wave formation for high  ultrasound pulse repetition frequencies lead to extensive reflections which our proposed method successfully  suppresses. Lastly, from our in-vivo experiments, we infer that our method is successful in reducing the indirect  auditory activities, however this benefit comes at a price of slight difference in targeted-location LFP activity  compared to the conventional method.  

Conclusion: The present results demonstrate the feasibility of our introduced approach for standing wave  suppression and improving the specificity of ultrasound energy delivery to the intended targeted location of  tFUS.  Significance: The present approach may lead to new means of tFUS experimental paradigm that allow tFUS  to be used with higher controllability at the targeted area and enhancing its penetration properties for further  studies of tFUS-induced activations in small animal models.