Ph.D Thesis

Ph.D StudentKrupa Steve
SubjectAdvances in Wavefront Engineered Ultrasonic Neuromodulation
DepartmentDepartment of Biomedical Engineering
Supervisor PROF. Shy Shoham


Recent discoveries on using Ultrasound for direct neural excitation and suppression of the Central Nervous System (CNS) have sparked a wave of investigations in models ranging from rodents to humans. Current studies employing low-resolution, fixed focus ultrasound transducers have demonstrated limited success in reliably eliciting neuronal excitation or inhibition in specific regions of the brain/ nervous system.  In contrast, acoustic fields engineered with high resolution, dynamic patterning in both the spatial and temporal domains (wavefront shaping) could provide a more robust solution to selectively excite or inhibit targeted regions within the CNS.   To date, non-invasive ultrasonic stimulation of the brain using acoustic fields modulated for specific spatio-temporal features has not been extensively studied or validated.

In this work, we explored spatial and temporal wavefront engineering in the context of ultrasonic neurostimulation.   First, we developed a custom in vivo research platform for evaluating the neurostimulation effects of advanced sonication strategies including rapid electronic beam scanning, mechanical line scanning, and newly-developed multi-focal holographic beamforming protocols. The high-resolution (mm-scale) acoustic fields, generated by a 2.3 MHz Insightec phased-array High Intensity Focused Ultrasound (HIFU) transducer, were applied to the cortex of anaesthetized rats with the goal of triggering quantifiable responses in the motor system.  A novel registration method was developed for aligning the HIFU’s and the stereotax’s coordinate systems, while electrical activity and responses in the motor system were captured via simultaneous, peri-stimulus recording of intramuscular EMG signals. Our experiments found that ultrasonic stimulation directed at the tail and hind-limb regions of the motor cortex elicited responses, whose effectiveness was dramatically increased when the ultrasound beam was dynamically scanned across the cortical targets of interest.    Next, we investigated the potential benefit of temporal wavefront shaping by using computer modeling to study the effect of pressure asymmetries in the ultrasonic stimulus.   The Neuronal Intramembrane Cavitation Excitation (NICE) computational framework was used to predict the firing response of rat pyramidal neurons stimulated by harmonically generated pressure-biased acoustic fields.  Interestingly, the model results do not indicate that such pressure biased fields will carry a definite advantage in this application in comparison to the baseline single-frequency acoustic stimulus.

Our results both validate and reinforce the use of certain wavefront engineering techniques within the field of ultrasonic neuromodulation, and motivates future research to explore and refine the stimulation protocols and parameters introduced in this work.