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Background Transcranial focused ultrasound (FUS) is gaining momentum as a novel non-invasive brain stimulation method, with promising potential for superior spatial resolution and depth penetration compared to transcranial magnetic stimulation or transcranial direct current stimulation. We examined the presence of tactile sensations elicited by FUS stimulation of two separate brain regions in humans—the primary (SI) and secondary (SII) somatosensory areas of the hand, as guided by individual-specific functional magnetic resonance imaging data. Results Under image-guidance, acoustic stimulations were delivered to the SI and SII areas either separately or simultaneously. The SII areas were divided into sub-regions that are activated by four types of external tactile sensations to the palmar side of the right hand—vibrotactile, pressure, warmth, and coolness. Across the stimulation conditions (SI only, SII only, SI and SII simultaneously), participants reported various types of tactile sensations that arose from the hand contralateral to the stimulation, such as the palm/back of the hand or as single/neighboring fingers. The type of tactile sensations did not match the sensations that are associated with specific sub-regions in the SII. The neuro-stimulatory effects of FUS were transient and reversible, and the procedure did not cause any adverse changes or discomforts in the subject’s mental/physical status. Conclusions The use of multiple FUS transducers allowed for simultaneous stimulation of the SI/SII in the same hemisphere and elicited various tactile sensations in the absence of any external sensory stimuli. Stimulation of the SII area alone could also induce perception of tactile sensations. The ability to stimulate multiple brain areas in a spatially restricted fashion can be used to study causal relationships between regional brain activities and their cognitive/behavioral outcomes.

In recent years there has been a considerable improvement in the quality of ultrasound (US) imaging. The integration of 3D US with neuronavigation technology has created an efficient and inexpensive tool for intra-operative imaging in neurosurgery. In this review we present the technological background and an overview of the wide range of different applications. The technology has so far mostly been applied to improve surgery of tumours in brain tissue, but it has also been found to be useful in other procedures such as operations for cavernous haemangiomas, skull base tumours, syringomyelia, medulla tumours, aneurysms, AVMs and endoscopy guidance.

New animal models of Zika virus (ZIKV) infection are imperative to accelerating efforts to treat or prevent disease in humans. Adams Waldorf et al . now report that ZIKV infection of a pregnant female pigtailed macaque caused brain lesions in the developing fetus, suggesting that this model may be useful for understanding ZIKV-associated congenital abnormalities in humans. We describe the development of fetal brain lesions after Zika virus (ZIKV) inoculation in a pregnant pigtail macaque. Periventricular lesions developed within 10 d and evolved asymmetrically in the occipital–parietal lobes. Fetal autopsy revealed ZIKV in the brain and significant cerebral white matter hypoplasia, periventricular white matter gliosis, and axonal and ependymal injury. Our observation of ZIKV-associated fetal brain lesions in a nonhuman primate provides a model for therapeutic evaluation.

Neuroimaging modalities such as MRI and EEG are able to record from the whole brain, but this comes at the price of either limited spatiotemporal resolution or limited sensitivity. Here, we show that functional ultrasound imaging (fUS) of the brain is able to assess local changes in cerebral blood volume during cognitive tasks, with sufficient temporal resolution to measure the directional propagation of signals. In two macaques, we observed an abrupt transient change in supplementary eye field (SEF) activity when animals were required to modify their behaviour associated with a change of saccade tasks. SEF activation could be observed in a single trial, without averaging. Simultaneous imaging of anterior cingulate cortex and SEF revealed a time delay in the directional functional connectivity of 0.27 ± 0.07 s and 0.9 ± 0.2 s for both animals. Cerebral hemodynamics of large brain areas can be measured at high spatiotemporal resolution using fUS. Neuroimaging modalities such as MRI and EEG are able to record brain activity, but spatiotemporal resolution and sensitivity are limited. Here, the authors show how a recently developed method, functional ultrasound imaging (fUS), can measure brain activation during cognitive tasks in primates.

Background Reliable intraoperative resection control during surgery of malignant brain tumours is associated with the longer overall survival of patients. B-mode ultrasound (BUS) is a familiar intraoperative imaging application in neurosurgical procedures and supplies excellent image quality. However, due to resection-induced artefacts, its ability to distinguish between tumour borders, oedema, surrounding tissue and tumour remnants is sometimes limited. In experienced hands, this “bright rim effect” could be reduced. However, it should be determined, if contrast-enhanced ultrasound can improve this situation by providing high-quality imaging during the resection. The aim of this clinical study was to examine contrast-enhanced and three-dimensional reconstructed ultrasound (3D CEUS) in brain tumour surgery regarding the uptake of contrast agent pre- and post-tumour resection, imaging quality and in comparison with postoperative magnetic resonance imaging in different tumour entities. Methods Fifty patients, suffering from various brain tumours intra-axial and extra-axial, who had all undergone surgery with the support of neuronavigation in our neurosurgical department, were included in the study. Their median age was 56 years (range, 28–79). Ultrasound imaging was performed before the Dura was opened and for resection control at the end of tumour resection as defined by the neurosurgeon. A high-end ultrasound (US) device (Toshiba Aplio XG®) with linear and sector probes for B-mode and CEUS was used. Navigation and 3D reconstruction were performed with a LOCALITE SonoNavigator® and the images were transferred digitally (DVI) to the navigation system. The contrast agent consists of echoic micro-bubbles showing tumour vascularisation. The ultrasound images were compared with the corresponding postoperative MR data in order to determine the accuracy and imaging quality of the tumours and tumour remnants after resection. Results Different types of tumours were investigated. High, dynamic contrast agent uptake was observed in 19 of 21 patients (90 %) suffering from glioblastoma, while in 2 patients uptake was low and insufficient. In 52.4 % of glioblastoma and grade III astrocytoma patients CEUS led to an improved delineation in comparison to BUS and showed a high-resolution imaging quality of the tumour margins and tumour boarders. Grade II and grade III astrocytoma ( n  = 6) as well as metastasis ( n  = 18) also showed high contrast agent uptake, which led in 50 % to an improved imaging quality. In 5 of these 17 patients, intraoperative CEUS for resection control showed tumour remnants, leading to further tumour resection. Patients treated with CEUS showed no increased neurological deficits after tumour resection. No pharmacological side-effects occurred. Conclusions Three-dimensional CEUS is a reliable intraoperative imaging modality and could improve imaging quality. Ninety percent of the high-grade gliomas (HGG, glioblastoma and astrocytoma grade III) showed high contrast uptake with an improved imaging quality in more than 50 %. Gross total resection and incomplete resection of glioblastoma were adequately highlighted by 3D CEUS intraoperatively. The application of US contrast agent could be a helpful imaging tool, especially for resection control in glioblastoma surgery.

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.

Long-range coherences in spontaneous brain activity reflect functional connectivity. Here we propose a novel, highly resolved connectivity mapping approach, using ultrafast functional ultrasound (fUS), which enables imaging of cerebral microvascular haemodynamics deep in the anaesthetized rodent brain, through a large thinned-skull cranial window, with pixel dimensions of 100 μm × 100 μm in-plane. The millisecond-range temporal resolution allows unambiguous cancellation of low-frequency cardio-respiratory noise. Both seed-based and singular value decomposition analysis of spatial coherences in the low-frequency (<0.1 Hz) spontaneous fUS signal fluctuations reproducibly report, at different coronal planes, overlapping high-contrast, intrinsic functional connectivity patterns. These patterns are similar to major functional networks described in humans by resting-state fMRI, such as the lateral task-dependent network putatively anticorrelated with the midline default-mode network. These results introduce fUS as a powerful novel neuroimaging method, which could be extended to portable systems for three-dimensional functional connectivity imaging in awake and freely moving rodents. Functional connectivity of brain networks is poorly understood, in part, due to limited imaging approaches. Here, the authors use ultrasound imaging to study functional connectivity in the adult rat brain in vivo , allowing for the identification of highly contrasted intrinsic connectivity patterns.

Functional ultrasound imaging and electroencephalography are combined to assess brain activity in mobile rats. The methodology is applied to the analysis of theta rhythms in a maze task and of epileptic seizures. We developed an integrated experimental framework that extends the brain exploration capabilities of functional ultrasound imaging to awake and mobile rats. In addition to acquiring hemodynamic data, this method further allows parallel access to electroencephalography (EEG) recordings of neuronal activity. We illustrate this approach with two proofs of concept: a behavioral study on theta rhythm activation in a maze running task and a disease-related study on spontaneous epileptic seizures.

A miniaturized ultrasound probe enables functional brain imaging in freely behaving rats. The large field of view and deep penetration makes this technique complementary to optical imaging approaches. Innovative imaging methods help to investigate the complex relationship between brain activity and behavior in freely moving animals. Functional ultrasound (fUS) is an imaging modality suitable for recording cerebral blood volume (CBV) dynamics in the whole brain but has so far been used only in head-fixed and anesthetized rodents. We designed a fUS device for tethered brain imaging in freely moving rats based on a miniaturized ultrasound probe and a custom-made ultrasound scanner. We monitored CBV changes in rats during various behavioral states such as quiet rest, after whisker or visual stimulations, and in a food-reinforced operant task. We show that fUS imaging in freely moving rats could efficiently decode brain activity in real time.

Objective To investigate the clinical significance of intraoperative B⁃ultrasound real⁃ time monitoring in craniotomy for patients with severe traumatic brain injury (sTBI). Methods From March 2017 to June 2019, 64 patients withs TBI who met the admission criteria were in cluded in the study. Craniotomy and/or decompressiv ecraniectomy were performed. According to the application of real⁃time B⁃ultrasound⁃guided surgery, the patients were randomly divided into 2 groups: ultrasound group (n=32) and control group (n=32). The operation time, the number of new hematoma during and after operation, the probability of bone flap removal, the probability of second operation and Glasgow Coma Scale (GCS) score were recorded. Glasgow Outcome Scale (GOS) was used to evaluate the prognosis and calculate the good prognosisrate. Results In the ultrasound group, 32 cases were successfully operated under the guidance of B⁃ultrasound, and the detection rate of new hematoma was 76% (19/25). The rate of hematoma clearance rate >90% [84.38% (27/32) vs. 59.38% (19/32); χ2=4.947, P=0.026], GCS score at 3 d after operation (11.38±3.54vs.9.19±3.81; t=2.382, P=0.020) and good prognosis rate at discharge [56.25% (18/32) vs. 31.25% (10/32) ; χ2=0.077, P=0.038] in the ultrasound group were higher than those in the control group, but there were no significant differences in the operation time, the probability of bone flap removal and the probability of second operation between 2 groups (P>0.05,forall). Conclusions Intraoperativ ereal⁃time B⁃ultrasound⁃guided surgery can improve the prognosis of patients withs TBI. DOI：10.3969/j.issn.1672⁃6731.2020.08.007