Wearable Transcranial Ultrasound System for Remote Stimulation of Freely Moving Animal.

OBJECTIVE: Transcranial focused ultrasound (tFUS) has drawn considerable attention in the neuroscience field as a noninvasive approach to modulate brain circuits. However, the conventional approach requires the use of anesthetized or immobilized animal models, which places considerable restrictions on behavior and affects treatment. Thus, this work presents a wireless, wearable system to achieve ultrasound brain stimulation in freely behaving animals. METHODS: The wearable tFUS system was developed based on a microcontroller and amplifier circuit. Brain activity induced by tFUS was monitored through cerebral hemodynamic changes using near-infrared spectroscopy. The system was also applied to stroke rehabilitation after temporal middle cerebral artery occlusion (tMCAO) in rats. Temperature calculations and histological results showed the safety of the application even with prolonged 40 min sonication. RESULTS: The output ultrasonic wave produced from a custom PZT transducer had a central frequency of 457 kHz and peak to peak pressure of 426 kPa. The device weight was 20 g, allowing a full range of motion. The stimulation was found to induce hemodynamic changes in the sonicated area, while open-field tests showed that ultrasound applied to the ipsilateral hemisphere for 5 consecutive days after the stroke facilitated recovery. CONCLUSION: The wearable tFUS system has been designed and implemented on moving rats. The results showed the ability of device to cause both short- and long lasting effects. SIGNIFICANCE: The proposed device provides a more natural environment to investigate the effects of tFUS for behavioral and long-term studies.

Non-invasive measurement of hemodynamic change during 8 MHz transcranial focused ultrasound stimulation using near-infrared spectroscopy.

BACKGROUND: Transcranial focused ultrasound (tFUS) attracts wide attention in neuroscience as an effective noninvasive approach to modulate brain circuits. In spite of this, the effects of tFUS on the brain is still unclear, and further investigation is needed. The present study proposes to use near-infrared spectroscopy (NIRS) to observe cerebral hemodynamic change caused by tFUS in a noninvasive manner. RESULTS: The results show a transient increase of oxyhemoglobin and decrease of deoxyhemoglobin concentration in the mouse model induced by ultrasound stimulation of the somatosensory cortex with a frequency of 8 MHz but not in sham. In addition, the amplitude of hemodynamics change can be related to the peak intensity of the acoustic wave. CONCLUSION: High frequency 8 MHz ultrasound was shown to induce hemodynamic changes measured using NIRS through the intact mouse head. The implementation of NIRS offers the possibility of investigating brain response noninvasively for different tFUS parameters through cerebral hemodynamic change.

Mobile Wireless Low-intensity Transcranial Ultrasound Stimulation System for Freely Behaving Small Animals.

Transcranial ultrasound stimulation (tUS) is a promising noninvasive approach to modulate brain circuits. While low-intensity tUS is putatively safe and has already been used for human participants, pre-clinical studies that aim to determine the effects of tUS on the brain still need to be carried out. Conventional tUS stimulation, however, requires the use of the anesthetized or immobilized animal model, which can place considerable restrictions on behavior. Thus, this work presents a portable, low cost, wireless system to achieve ultrasound brain stimulation in freely behaving animals. The tUS system was developed based on a commercial 16 MHz microcontroller and amplifier circuit. The acoustic wave with a central frequency of 450 kHz was generated from a 5mm PZT with a peak pressure of 426 kPa. The wireless tUS with a total weight of 20 g was placed on the back of the rat allowing the animal a full range of unimpeded motion. The mobile ultrasound system was able to induce a robust ear movement as a response to stimulation of the motor cortex. The outcome demonstrates the ability of wireless tUS to modulate the brain circuit of a freely behaving rat. The portability of the whole system provides a more natural environment for investigating the effect of tUS on behavior and chronic studies.

Simultaneous Monitoring of Hemodynamic Response in the Pre-Frontal Cortex and Genital Organ During Sexual Arousal Using Near-Infrared Spectroscopy.

BACKGROUND: The monitoring of brain activity along with genital organ response to sexual stimulation can play an important role in understanding the under-lying mechanisms of sexual arousal as well as diagnosing erectile dysfunction. Several studies have observed brain activity corresponding to sexual stimuli, but only a few studies have shown a simultaneous measurement of brain activation and penile response. AIM: To introduce near-infrared spectroscopy (NIRS) as a portable, easily implemented, and low-cost technique to simultaneously record brain activity and hemodynamics in the genital organ during sexual arousal. METHODS: Hemodynamic measurements of 15 healthy men were obtained using a home-built NIRS system. In the initial experiment, hemodynamics in the pre-frontal cortex (N = 10) were measured during visual sexual stimulation (VSS) and neutral visual stimulation (NVS) to identify brain activity related to sexual arousal. In the subsequent experiment, cerebral and penile hemodynamics were simultaneously measured (N = 5) using NIRS during VSS and NVS. RESULTS: The pre-frontal cortex showed activity related to VSS but not to NVS. Simultaneous measurements showed a corresponding increase of penile oxygenated and deoxygenated hemoglobin concentration indicating an increase of blood volume associated with sexual arousal in healthy men. An average response delay of 4 seconds was observed in the hemodynamic changes between the brain and genital organ. CONCLUSION: In this preliminary study, we presented a NIRS system capable not only of detecting cerebral hemodynamic changes related to sexual arousal but also the simultaneous measurement of penile hemodynamics. We believe the NIRS system can be a potential technique to supplement the field of sexual medicine and can be expanded further to diagnose erectile dysfunction. Kim E, Kim S, Zephaniah PV, et al. Simultaneous Monitoring of Hemodynamic Response in the Pre-Frontal Cortex and Genital Organ During Sexual Arousal Using Near-Infrared Spectroscopy. Sex Med 2018;6:234-238.

Monitoring cerebral hemodynamic change during transcranial ultrasound stimulation using optical intrinsic signal imaging.

Transcranial ultrasound stimulation (tUS) is a promising non-invasive approach to modulate brain circuits. The application is gaining popularity, however the full effect of ultrasound stimulation is still unclear and further investigation is needed. This study aims to apply optical intrinsic signal imaging (OISI) for the first time, to simultaneously monitor the wide-field cerebral hemodynamic change during tUS on awake animal with high spatial and temporal resolution. Three stimulation paradigms were delivered using a single-element focused transducer operating at 425 kHz in pulsed mode having the same intensity (ISPPA = 1.84 W/cm2, ISPTA = 129 mW/cm2) but varying pulse repetition frequencies (PRF). The results indicate a concurrent hemodynamic change occurring with all actual tUS but not under a sham stimulation. The stimulation initiated the increase of oxygenated hemoglobin (HbO) and decrease of deoxygenated hemoglobin (RHb). A statistically significant difference (p < 0.05) was found in the amplitude change of hemodynamics evoked by varying PRF. Moreover, the acoustic stimulation was able to trigger a global as well as local cerebral hemodynamic alteration in the mouse cortex. Thus, the implementation of OISI offers the possibility of directly investigating brain response in an awake animal during tUS through cerebral hemodynamic change.