Acoustoelectric Imaging of Deep Brain Stimulation Currents

Abstract

Deep brain stimulation (DBS) is a surgical intervention that provides therapeutic relief ofmotor symptoms in Parkinson’s disease, essential tremor, and dystonia. Cumulatively, these diseases are prevalent in ~4% of the global population, primarily in those 50+ years old. Due to its success in treating pathological motor symptoms, the use of DBS has been explored for other brain disorders including depression, obsessive compulsive disorder, and Tourette’s syndrome. However, despite this success and subsequent expansion, the mechanisms underlying the therapeutic effects of DBS remain poorly understood. This limits engineer’s ability to design new electrodes or stimulating parameters, and clinician’s ability to optimally implement them, effectively reducing the care received by the patient. The main obstacle in optimizing DBS is a lack of in-vivo electrical feedback of the currents injected into the brain. As a result, the spread of current from a DBS electrode is predicted by computational simulations that similarly lack in-vivo feedback for validation. This study uses acoustoelectric imaging (AEI) to address this limitation. AEI uses ultrasound (US) to detect an induced modulation in current densities. Therefore, the spatial and temporal resolutions in AEI are limited by the center frequency and pulse rate of the US transducer, typically in the sub-mm and sub-ms ranges. Moreover, AEI can be performed entirely non-invasively, enabling real-time acquisition of DBS currents in a patient. However, due to attenuation from the skull, US frequencies are limited to <3MHz or >0.5mm spatial resolution. In this study, I use AEI to detect current pulses as short as 100μs and weak at 1.5 mA from two different DBS electrodes and through four different skulls. At 2.5 MHz, transcranial AEI accurately detects DBS currents with a spatial resolution of ~1.7mm, thereby enabling the determination of the exact contacts used during stimulation, even within a segmented ring of a current steering DBS electrode such as the St. Jude’s Infinity. I then demonstrate a phase-aberration correction method that significantly restores the lateral focal resolution and pressures in transcranial ultrasound by performing time-reversal operations on an electrical target. Lastly, clinical implications and future directions of AEI for DBS are discussed. These include use in DBS implantation surgeries, post-surgical chronic evaluations of stimulation integrity, the detection of isolated dipoles, the implementation of a more realistic skull, scalp, and brain phantom, the integration of AEI with neuronavigational equipment, and the steps required for direct estimation of neuronal activation from a 4D AE dataset of DBS currents.