Non-invasive neuromodulation instrument to assess neonatal brain function

Our preliminary data suggest that neurons exposed to hypoxic injury respond differently to ultrasound-induced stimulation compared to sham treated neurons. Based on these findings we hypothesize that: non-invasive neuromodulation is a tool for functional evaluation of neural injury. The use of ultrasound neuromodulation as a functional interrogation tool to measure the severity of neural injury is conceptually innovative. Ultrasound-mediated neural stimulation has not been used previously to assess the extent of brain injury. Last month, our team conducted ultrasound stimulation in an in vivo hypoxia experiment using three neonatal piglets. Figure 10A shows the experimental setup using single element ultrasound stimulation (500 KHz with 500 mV intensity, 400 msec excitation time and 10 second interval time) and EEG recording for validation. The piglet experienced ultrasound excitation for 15 minutes baseline (normal oxygen level), 45 minutes hypoxia (12% Oxygen) and 6 minutes asphyxia ( 0 air) and 35 minutes recovery (Figure 1B and 1C). Evoked potential was recorded during the whole experiment. Consistently, the amplitude of evoked potential was increased during hypoxia and was suppressed during asphyxia.

Figure 1. In vivo ultrasound stimulation in hypoxia experiment. (A) Diagram of the experimental setup. (B) An example of evoked potential changes during baseline (normal oxygenation) without ultrasound stimulation, and with ultrasound stimulation during baseline, hypoxia, asphyxia, and recovery. (C) Heat map showing the EEG power (red: high power; blude: low power) for the entire experiment duration.

Publications

  1. Kang J, Le HND, Zhang HK, Kang JU, Harraz MM, Boctor EM. Initial proof-of-concept of photoacoustic cell stimulation approach: preliminary in vitro study. Proc. SPIE 10052, Optogenetics and Optical Manipulation, 100520U (20 July 2017).
  2. Song H, Ray S, Kang J, Shishikura M, Harraz MM, Boctor EM. Differential Ultrasound Neuromodulatory Responses of Rat Primary Cortical Neurons (PCN) with Oxygen Deprivation in Vitro. IEEE IUS 2020.