Non-pharmacological and non-surgical transcranial modulation of the nerve function may provide new opportunities in evaluation and treatment of cranial nerve diseases. This study investigates the possibility of using low-intensity transcranial focused ultrasound (FUS) to selectively stimulate the rat abducens nerve located above the base of the skull. FUS (frequencies of 350 kHz and 650 kHz) operating in a pulsed mode was applied to the abducens nerve of Sprague-Dawley rats under stereotactic guidance. The abductive eyeball movement ipsilateral to the side of sonication was observed at 350 kHz, using the 0.36 msec tone burst duration (TBD), 1.5 kHz pulse repetition frequency (PRF), and the overall sonication duration of 200 msec. Histological and behavioral monitoring showed no signs of disruption in the blood brain barrier (BBB) as well as no damage to the nerves and adjacent brain tissue resulting from the sonication. As a novel functional neuro-modulatory modality, the pulsed application of FUS has potential in diagnostic and therapeutic applications in diseases of the peripheral nervous system.

We are developing virtual fixtures for the internal mammary artery (IMA) harvest portion of robot-assisted coronary artery bypass graft procedures. A preoperative CT scan will be processed to define the location of the IMA. In surgery, the patient's anatomy will be registered to the image data, then a virtual fixture will constrain the instrument's motions, as commanded by the surgeon, to appropriate paths adjacent to the artery. As a preliminary test, a virtual wall is implemented on a commercial surgical robot system. Results from a dissection task show that execution is faster and more precise than with conventional freehand techniques.

Regional modulation of the level of cortical neurotransmitters in the brain would serve as a new functional brain mapping technique to interrogate the neurochemical actions of the brain. We investigated the utility of the application of low-intensity, pulsed sonication of focused ultrasound (FUS) to the brain to modulate the extracellular level of dopamine (DA) and serotonin (5-HT). FUS was delivered to the thalamic areas of rats, and extracellular DA and 5-HT were sampled from the frontal lobe using the microdialysis technique. The concentration changes of the sampled DA and 5-HT were measured through high-performance liquid chromatography. We observed a significant increase of the extracellular concentrations of DA and 5-HT in the FUS-treated group as compared with those in the unsonicated group. Our results provide the first direct evidence that FUS sonication alters the level of extracellular concentration of these monoamine neurotransmitters and has a potential modulatory effect on their local release, uptake, or degradation. Our findings suggest that the pulsed application of FUS offers new perspectives for a possible noninvasive modulation of neurotransmitters and may have diagnostic as well as therapeutic implications for DA/5-HT-mediated neurological and psychiatric disorders.

Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer’s intention to stimulate a rat’s brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer’s intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.

Objective: Transcranial focused ultrasound (FUS), with its ability to non-invasively modulate the excitability of region-specific brain areas, is gaining attention as a potential neurotherapeutic modality. The aim of this study was to examine whether or not FUS administered to the brain could alter the extracellular levels of glutamate and γ-aminobutyric acid (GABA), which are representative excitatory and inhibitory amino acid neurotransmitters, respectively. Methods: FUS, delivered in the form of a train of pulses, was applied to the thalamus of Sprague-Dawley rats transcranially. Glutamate and GABA were directly sampled from the frontal lobe of the rat brain via a direct microdialysis technique before, during, and after the sonication. The dialysate concentrations were determined by high-performance liquid chromatography. Results: The individual levels of the neurotransmitters sampled were normalized to the baseline level for each rat. In terms of the changes in extracellular glutamate levels, there was no difference between the FUS-treated group and the unsonicated control group. However, extracellular GABA levels started to decrease upon sonication and remained reduced (approximately 20% below baseline; repeated-measures ANOVA, p < 0.05, adjusted for multiple comparisons) compared to the control group. Conclusion: The ability to modulate region-specific brain activity, along with the present evidence of the ability to modulate neurotransmission, demonstrates the potential utility of FUS as a completely new non-invasive therapeutic modality.

The results show that the human subject can perform the task more precisely and safely with the developed AR-based navigation system than with the conventional endoscopic system.

This study investigates the spatial profile and the temporal latency of the brain stimulation induced by the transcranial application of pulsed focused ultrasound (FUS). The site of neuromodulation was detected by using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) immediately after FUS sonication on the unilateral thalamic area of the Spague-Dawley rats. The latency of the stimulation was estimated by measuring the time taken from the onset of the stimulation of the appropriate brain motor area to the corresponding tail motor response. The brain area showing elevated glucose uptake from the PET image was much smaller (56±10% in diameter, 24±6% in length) than the size of the acoustic focus, which is conventionally defined by the full-width at half-maximum (FWHM) of the acoustic intensity field. The spatial dimension of the FUS-mediated neuromodulatory area was more localized, approximated to be full-width at 90%-maximum of the acoustic intensity field. In addition, the time delay of motor responses elicited by the FUS sonication was 171±63 (s.d.) ms from the onset of sonication. When compared to latencies of other non-ultrasonic neurostimulation techniques, the longer time delay associated with FUS-mediated motor responses is suggestive of the non-electrical modes of neuromodulation, making it a distinctive brain stimulation method.

The spatial specificity and controllability of focused ultrasound (FUS), in addition to its ability to modify the excitability of neural tissue, allows for the selective and reversible neuromodulation of the brain function, with great potential in neurotherapeutics. Intra-operative magnetic resonance imaging (MRI) guidance (in short, MRg) has limitations due to its complicated examination logistics, such as fixation through skull screws to mount the stereotactic frame, simultaneous sonication in the MRI environment, and restrictions in choosing MR-compatible materials. In order to overcome these limitations, an image-guidance system based on optical tracking and pre-operative imaging data is developed, separating the imaging acquisition for guidance and sonication procedure for treatment. Techniques to define the local coordinates of the focal point of sonication are presented. First, mechanical calibration detects the concentric rotational motion of a rigid-body optical tracker, attached to a straight rod mimicking the sonication path, pivoted at the virtual FUS focus. The spatial error presented in the mechanical calibration was compensated further by MRI-based calibration, which estimates the spatial offset between the navigated focal point and the ground-truth location of the sonication focus obtained from a temperature-sensitive MR sequence. MRI-based calibration offered a significant decrease in spatial errors (1.9±0.8 mm; 57% reduction) compared to the mechanical calibration method alone (4.4±0.9 mm). Using the presented method, pulse-mode FUS was applied to the motor area of the rat brain, and successfully stimulated the motor cortex. The presented techniques can be readily adapted for the transcranial application of FUS to intact human brain.