Qiuju Jiang

Noninvasive Ultrasonic Neuromodulation in Freely Moving Mice

Neuromodulation is a fundamental method for obtaining basic information about neuronal circuits for use in treatments for neurological and psychiatric disorders. Ultrasound stimulation has become a promising approach for noninvasively inducing neuromodulation in animals and humans. However, the previous investigations were subject to substantial limitations, due to most of them involving anesthetized and fixed small-animal models. Studies of awake and freely moving animals are needed, but the currently used ultrasound devices are too bulky to be applied to a freely moving animal. This study is the first time to design and fabricate a miniature and lightweight head-mounted ultrasound stimulator for inducing neuromodulation in freely moving mice. The main components of the stimulator include a miniature piezoelectric ceramic, a concave epoxy acoustic lens, and housing and connection components. The device was able to induce action potentials recorded in situ and evoke head-turning behaviors by stimulating the primary somatosensory cortex barrel field of the mouse. These findings indicate that the proposed method can be used to induce noninvasive neuromodulation in freely moving mice. This novel method could potentially lead to the application of ultrasonic neuromodulation in more-extensive neuroscience investigations.

Local field potentials responses of ultrasonic neuromodulation in freely moving mouse

Ultrasound (US) brain stimulation has been demonstrated to be a promising approach for noninvasive neuromodulation. However, traditional methods always demand animals to be under anesthesia and body constraint to achieve stable operation with bulky US transducer, while those demands would result in interference to the neural activity related to perception, cognition, and behavior. Appling a miniature US stimulator in freely moving mouse will greatly benefit for obtaining credible neural response from brain modulation. This study investigates the local field potentials (LFPs) responses of ultrasonic neuromodulation on freely moving mouse with a customized head-mounted US transducer. The stimulator mainly consist of a tiny piezoelectric ceramic, a concave epoxy acoustic lens, and some affiliated accessories for housing and connecting. The decrease of power spectral density at theta band and increase of power at delta band of local field potentials, indicate that the proposed head-mounted ultrasound stimulator can perform noninvasive neuromodulation on freely moving mouse. The proposed head-mounted US device could potentially promote the development of ultrasonic neuromodulation to more extensive neuroscience studies.

Temporal Neuromodulation of Retinal Ganglion Cells by Low-Frequency Focused Ultrasound Stimulation

Significant progress has been made recently in treating neurological blindness using implantable visual prostheses. However, implantable medical devices are highly invasive and subject to many safety, efficacy, and cost issues. The discovery that ultrasound (US) may be useful as a noninvasive neuromodulation tool has aroused great interest in the field of acoustic retinal prostheses (ARPs). We have investigated the responsiveness of rat retinal ganglion cells (RGCs) to low-frequency focused US stimulation (LFUS) at 2.25 MHz and characterized the neurophysiological properties of US responses by performing in vitro multielectrode array recordings. The results show that LFUS can reliably activate RGCs. The US-induced responses did not correspond to the standard light responses and varied greatly among cell types. Moreover, dual-peak responses to US stimulation were observed that have not been reported previously. The temporal response properties of RGCs, including their latency, firing rate, and response type, were modulated by the acoustic intensity. These findings suggest the presence of a temporal neuromodulation effect of LFUS and potentially open a new avenue in the development of ARP.

Local field potentials responses to ultrasonic neuromodulaton on freely moving mouse

Ultrasound (US) brain stimulation has been demonstrated to be a promising approach for noninvasive neuromodulation. However, traditional methods always demand animals to be under anesthesia and body constraint to achieve stable operation with bulky US transducer, while those demands would result in interference to the neural activity related to perception, cognition, and behavior. Appling a miniature US stimulator on freely moving mouse will greatly benefit for obtaining credible neural response from ultrasonic neuromodulation. This study investigates the local field potentials (LFPs) responses to ultrasonic neuromodulation on freely moving mouse by using a customized head-mounted US transducer.

Retina stimulation on rat in vivo with low-frequency ultrasound

More and more researches are exploring the neurostimulation effect of ultrasound (US) on the central nervous system (e.g. brain and retina) and the peripheral nervous system (such as skin). US stimulation has been regarded as a new noninvasive neurostimulation approach by many researchers. Our previous studies had shown that the temporal response patterns of RGCs could be stimulated by US in vitro. In this article, we apply low-frequency (2.25 MHz) focused US stimulation to the rat retina in vivo to investigate the effect on the primary visual cortex.

Visualization of blood flow in brain tumor in small animal with ultrafast ultrasound

How to precisely evaluate the characteristics of glioma tumor in vivo is a challenging question for surgical resection clinically. Due to the infiltration feature of the tumor, precise resection remains challenging because of the uncertainties of surrounding vasculature. The sensitivity of flow measurement is improved by ultrafast plane-wave imaging which is capable of delineating the flow information in the brain. In this study, we first time visualize the blood flow distribution of glioma tumor in a small animal with plane-wave Doppler ultrasound imaging method, yielding highly resolved neurovascular map of the glioma.

Noninvasive neurostimulation on mice by 5 MHz ultrasound

Ultrasound has been demonstrated to be an effective approach for noninvasive neurostimulation. Low frequency ultrasound (<;1 MHz) is preferable as its low ultrasonic attenuation when passing through the skull. High frequency ultrasound is able to provide reduced size of focal region. However, the performance of stimulation with high frequency ultrasound is not proved yet. This study examines the feasibility and effectiveness of using high frequency, i.e. 5 MHz, focused ultrasound to perform the neurostimulation on mice. The acoustic properties of 1 MHz and 5 MHz ultrasound on mouse skull were evaluated by a 3D acoustic scanning system. By performing proper acoustic compensation, 1 MHz and 5 MHz ultrasound can present the same acoustic intensity level after passing the skull. They were used to do the brain stimulation with same group of mice. Electromyography (EMG) signals collected from tail muscles and videos of motion responses were analyzed for the evaluation of neurostimulation. The results illustrated that 5 MHz ultrasound can successfully achieve the neurostimulation by monitoring the EMG and motion responses. The equivalent diameter (D) of stimulus for 5 MHz is significantly smaller than that of 1 MHz. Focused ultrasound with higher frequency can provide smaller size of stimulation region, which offers precise control of the neurostimulation in a non-invasive manner.