The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation.

Transcranial low-intensity ultrasound is a promising neuromodulation modality, with the advantages of noninvasiveness, deep penetration, and high spatiotemporal accuracy. However, the underlying biological mechanism of ultrasonic neuromodulation remains unclear, hindering the development of efficacious treatments. Here, the well-known Piezo1 was studied through a conditional knockout mouse model as a major mediator for ultrasound neuromodulation ex vivo and in vivo. We showed that Piezo1 knockout (P1KO) in the right motor cortex of mice significantly reduced ultrasound-induced neuronal calcium responses, limb movement, and muscle electromyogram (EMG) responses. We also detected higher Piezo1 expression in the central amygdala (CEA), which was found to be more sensitive to ultrasound stimulation than the cortex was. Knocking out the Piezo1 in CEA neurons showed a significant reduction of response under ultrasound stimulation, while knocking out astrocytic Piezo1 showed no-obvious changes in neuronal responses. Additionally, we excluded an auditory confound by monitoring auditory cortical activation and using smooth waveform ultrasound with randomized parameters to stimulate P1KO ipsilateral and contralateral regions of the same brain and recording evoked movement in the corresponding limb. Thus, we demonstrate that Piezo1 is functionally expressed in different brain regions and that it is an important mediator of ultrasound neuromodulation in the brain, laying the ground for further mechanistic studies of ultrasound.

Transcranial ultrasound stimulation selectively affects cortical neurovascular coupling across neuronal types and LFP frequency bands.

Previous studies have affirmed that transcranial ultrasound stimulation (TUS) can influence cortical neurovascular coupling across low-frequency (0-2 Hz)/high-frequency (160-200 Hz) neural oscillations and hemodynamics. Nevertheless, the selectivity of this coupling triggered by transcranial ultrasound stimulation for spike activity (> 300 Hz) and additional frequency bands (4-150 Hz) remains elusive. We applied transcranial ultrasound stimulation to mice visual cortex while simultaneously recording total hemoglobin concentration, spike activity, and local field potentials. Our findings include (1) a significant increase in coupling strength between spike firing rates of putative inhibitory neurons/putative excitatory neurons and total hemoglobin concentration post-transcranial ultrasound stimulation; (2) an ~ 2.1-fold higher Pearson correlation coefficient between putative inhibitory neurons and total hemoglobin concentration compared with putative excitatory neurons and total hemoglobin concentration (*P < 0.05); (3) a notably greater cross-correlation between putative inhibitory neurons and total hemoglobin concentration than that between putative excitatory neurons and total hemoglobin concentration (*P < 0.05); (4) an enhancement of Pearson correlation coefficient between the relative power of γ frequency band (30-80 Hz), hγ frequency band (80-150 Hz) and total hemoglobin concentration following transcranial ultrasound stimulation (*P < 0.05); and (5) strongest cross-correlation observed at negative delay for θ frequency band, and positive delay for α, ß, γ, hγ frequency bands. Collectively, these results demonstrate that cortical neurovascular coupling evoked by transcranial ultrasound stimulation exhibits selectivity concerning neuronal types and local field potential frequency bands.

Effects of the motor cortical theta-burst transcranial-focused ultrasound stimulation on the contralateral motor cortex.

Theta-burst transcranial ultrasound stimulation (tbTUS) increases primary motor cortex (M1) excitability for at least 30 min. However, the remote effects of focal M1 tbTUS on the excitability of other cortical areas are unknown. Here, we examined the effects of left M1 tbTUS on right M1 excitability. An 80 s train of active or sham tbTUS was delivered to the left M1 in 20 healthy subjects. Before and after the tbTUS, we measured: (1) corticospinal excitability using motor-evoked potential (MEP) amplitudes from single-pulse transcranial magnetic stimulation (TMS) of left and right M1; (2) interhemispheric inhibition (IHI) from left to right M1 and from right to left M1 using a dual-site paired-pulse TMS paradigm; and (3) intracortical circuits of the right M1 with short-interval intracortical inhibition and intracortical facilitation (ICF) using paired-pulse TMS. Left M1 tbTUS decreased right M1 excitability as shown by decreased MEP amplitudes, increased right M1 ICF and decreased short-interval IHI from left to right hemisphere at interstimulus interval (ISI) of 10 ms but not long-interval IHI at interstimulus interval of 40 ms. The study showed that left M1 tbTUS can change the excitability of remote cortical areas with decreased right M1 excitability and interhemispheric inhibition. The remote effects of tbTUS should be considered when it is used in neuroscience research and as a potential neuromodulation treatment for brain disorders. KEY POINTS: Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique for neuromodulation with the advantages of being able to achieve high spatial resolution and target deep brain structures. A repetitive TUS protocol, with an 80 s train of theta burst patterned TUS (tbTUS), has been shown to increase primary motor cortex (M1) excitability, as well as increase alpha and beta movement-related spectral power in distinct brain regions. In this study, we examined on the effects of the motor cortical tbTUS on the excitability of contralateral M1 measured with MEPs elicited by transcranial magnetic stimulation. We showed that left M1 tbTUS decreased right M1 excitability and left-to-right M1 interhemispheric inhibition, and increased intracortical facilitation of right M1. These results lead to better understand the effects of tbTUS and can help the development of tbTUS for the treatment of neurological and psychiatric disorders and in neuroscience research.

Low-intensity transcranial ultrasound stimulation improves memory in vascular dementia by enhancing neuronal activity and promoting spine formation.

Memory is closely associated with neuronal activity and dendritic spine formation. Low-intensity transcranial ultrasound stimulation (TUS) improves the memory of individuals with vascular dementia (VD). However, it is unclear whether neuronal activity and dendritic spine formation under ultrasound stimulation are involved in memory improvement in VD. In this study, we found that seven days of TUS improved memory in VD model while simultaneously increasing pyramidal neuron activity, promoting dendritic spine formation, and reducing dendritic spine elimination. These effects lasted for 7 days but disappeared on 14 d after TUS. Neuronal activity and dendritic spine formation strongly corresponded to improvements in memory behavior over time. In addition, we also found that the memory, neuronal activity and dendritic spine of VD mice cannot be restored again by TUS of 7 days after 28 d. Collectively, these findings suggest that TUS increases neuronal activity and promotes dendritic spine formation and is thus important for improving memory in patients with VD.

Plasticity-Induced Effects of Theta Burst Transcranial Ultrasound Stimulation in Parkinson's Disease.

BACKGROUND: Low-intensity transcranial ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) technique with high spatial specificity. Previous studies showed that TUS delivered in a theta burst pattern (tbTUS) increased motor cortex (MI) excitability up to 30 minutes due to long-term potentiation (LTP)-like plasticity. Studies using other forms of NIBS suggested that cortical plasticity may be impaired in patients with Parkinson's disease (PD). OBJECTIVE: The aim was to investigate the neurophysiological effects of tbTUS in PD patients off and on dopaminergic medications compared to healthy controls. METHODS: We studied 20 moderately affected PD patients in on and off dopaminergic medication states (7 with and 13 without dyskinesia) and 17 age-matched healthy controls in a case-controlled study. tbTUS was applied for 80 seconds to the MI. Motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), and short-interval intracortical facilitation (SICF) were recorded at baseline, and at 5 minutes (T5), T30, and T60 after tbTUS. Motor Unified Parkinson's Disease Rating Scale (mUPDRS) was measured at baseline and T60. RESULTS: tbTUS significantly increased MEP amplitude at T30 compared to baseline in controls and in PD patients on but not in PD patients off medications. SICI was reduced in PD off medications compared to controls. tbTUS did not change in SICI or SICF. The bradykinesia subscore of mUPDRS was reduced at T60 compared to baseline in PD on but not in the off medication state. The presence of dyskinesia did not affect tbTUS-induced plasticity. CONCLUSIONS: tbTUS-induced LTP plasticity is impaired in PD patients off medications and is restored by dopaminergic medications. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Modulation effect of low-intensity transcranial ultrasound stimulation on REM and NREM sleep.

Previous studies have shown that modulating neural activity can affect rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Low-intensity transcranial ultrasound stimulation (TUS) can effectively modulate neural activity. However, the modulation effect of TUS on REM and NREM sleep is still unclear. In this study, we used ultrasound to stimulate motor cortex and hippocampus, respectively, and found the following: (i) In healthy mice, TUS increased the NREM sleep ratio and decreased the REM sleep ratio, and altered the relative power and sample entropy of the delta band and spindle in NREM sleep and that of the theta and gamma bands in REM sleep. (ii) In sleep-deprived mice, TUS decreased the ratio of REM sleep or the relative power of the theta band during REM sleep. (iii) In sleep-disordered Alzheimer's disease (AD) mice, TUS increased the total sleep time and the ratio of NREM sleep and modulated the relative power and the sample entropy of the delta and spindle bands during NREM and that of the theta band during REM sleep. These results demonstrated that TUS can effectively modulate REM and NREM sleep and that modulation effect depends on the sleep state of the samples, and can improve sleep in sleep-disordered AD mice.

Transcranial ultrasound stimulation modulates neural activities during NREM and REM depending on the stimulation phase of slow oscillations and theta waves in the hippocampus.

Modulation of the hippocampal neural activity by low-intensity transcranial ultrasound stimulation depends on the phase of theta rhythm and can also regulate sleep rhythm. However, until now, the modulatory effect of ultrasound stimulation on neural activity in different sleep states depending on the phase of local field potential stimulation in the hippocampus was unclear. To answer this question, closed-loop ultrasound stimulation was applied to in-phase (upstate)/out-of-phase slow oscillations in the hippocampus during non-rapid eye movement sleep, and to the peaks and troughs of theta oscillations in the hippocampus during wake in a mouse model. Local field potential of the hippocampus within 3-h after the ultrasound stimulation during light-on sleep cycle was recorded. We found that (i) under slow-oscillation in-phase stimulation, ultrasound stimulation upregulated the non-rapid eye movement ratio and decreased the wake ratio. Furthermore, it increased the ripple density during non-rapid eye movement and enhanced the coupling of the spindle-ripple during non-rapid eye movement as well as the theta-high gamma phase-amplitude coupling during the REM period. In addition, theta during the REM period showed a more stable oscillation mode. (ii) Under slow-oscillation out-of-phase stimulation, ultrasound stimulation increased the density of ripple during non-rapid eye movement and enhanced the theta-high gamma phase-amplitude coupling strength during REM. Furthermore, theta oscillations during REM were significantly slower and showed higher variability. (iii) Under the phase-locked peak and trough stimulation of theta oscillation, ultrasound stimulation increased the ripple density during non-rapid eye movement, weakened the coupling strength of spindle-ripple during non-rapid eye movement, and enhanced theta-high gamma phase-amplitude coupling during REM. However, theta oscillation mode was not changed significantly during REM. The above results suggest that the regulatory effect of ultrasound stimulation on neural activity in different sleep states depends on the stimulation phases of slow oscillations and theta waves in the hippocampus.

Transcranial ultrasound with electrical stimulation of the cerebello-parietal nucleus on cerebral blood flow and limb function in patients with stroke.

OBJECTIVE: To investigate the efficacy of transcranial ultrasound stimulation (TUS) combined with Fastigial nucleus stimulation (FNS) on cerebral blood flow and limb function in patients in the acute phase of ischemic stroke. METHODS: A total of 90 patients in the acute phase of ischemic stroke were randomly divided into an FNS, TUS, and TUS + FNS group (30 patients each), and all patients also received conventional treatment. The FNS group was treated with FNS alone. The TUS group was treated with TUS alone. The TUS + FNS group was treated with both TUS and FNS. The three groups were treated once a day for 6 days a week. RESULTS: The simplified Fugl-Meyer Assessment (FMA) and Barthel index scores (BI), and the peak systolic blood flow velocity (Vs) and the mean blood flow velocity (Vm) of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery, were significantly higher in all three groups compared with before treatment (P < 0.05). The scores for the TUS group were higher than for the FNS group (P < 0.05), and the scores of the TUS + FNS group were higher than the TUS and FNS groups, respectively (P < 0.05). The total effective rate was 63.3%, 70.0%, and 90.0% in the FNS, TUS, and TUS + FNS groups, respectively, and the difference between the three groups was statistically significant (P < 0.05). CONCLUSION: The FNS and TUS treatments improved the function of and accelerated cerebral blood flow in patients with acute ischemic stroke to different degrees, and the combined use of both treatment types was overall more effective.

Robotic Assisted Transcranial Doppler Monitoring in Acute Neurovascular Care: A Feasibility and Safety Study.

BACKGROUND: Transcranial color Doppler (TCD) is currently the only noninvasive bedside tool capable of providing real-time information on cerebral hemodynamics. However, being operator dependent, TCD monitoring is not feasible in many institutions. Robotic assisted TCD (ra-TCD) was recently developed to overcome these constraints. The aim of this study was to evaluate the safety and feasibility of cerebral monitoring with a novel ra-TCD in acute neurovascular care. METHODS: This is a two-center prospective study conducted between August 2021 and February 2022 at Padua University Hospital (Padua, Italy) and Kepler University Hospital (Linz, Austria). Adult patients with conditions impacting cerebral hemodynamics or patients undergoing invasive procedures affecting cerebral hemodynamics were recruited for prolonged monitoring (> 30 min) of the middle cerebral artery with a novel ra-TCD (NovaGuide Intelligent Ultrasound, NeuraSignal, Los Angeles, CA). Manual TCD was also performed for comparison by an experienced operator. Feasibility and safety rates were recorded. RESULTS: A total of 92 patients (age: mean 68.5 years, range 36-91; sex: male 57 [62%]) were enrolled in the two centers: 54 in Padua, 38 in Linz. The examination was feasible in the majority of patients (85.9%); the head cradle design and its radiopacity hindered its use during carotid endarterectomy and mechanical thrombectomy. Regarding safety, only one patient (1.1%) reported a minor local edema due to prolonged probe pressure. Velocity values were similar between ra-TCD and manual TCD. CONCLUSIONS: This novel ra-TCD showed an excellent safety and feasibility and proved to be as reliable as manual TCD in detecting blood flow velocities. These findings support its wider use for cerebral hemodynamics monitoring in acute neurovascular care. However, further technical improvements are needed to expand the range of applicable settings.

Noninvasive intervention by transcranial ultrasound stimulation: Modulation of neural circuits and its clinical perspectives.

Low-intensity focused transcranial ultrasound stimulation (TUS) is an emerging noninvasive technique capable of stimulating both the cerebral cortex and deep brain structures with high spatial precision. This method is recognized for its potential to comprehensively perturb various brain regions, enabling the modulation of neural circuits, in a manner not achievable through conventional magnetic or electrical brain stimulation techniques. The underlying mechanisms of neuromodulation are based on a phenomenon where mechanical waves of ultrasound kinetically interact with neurons, specifically affecting neuronal membranes and mechanosensitive channels. This interaction induces alterations in the excitability of neurons within the stimulated region. In this review, we briefly present the fundamental principles of ultrasound physics and the physiological mechanisms of TUS neuromodulation. We explain the experimental apparatus and procedures for TUS in humans. Due to the focality, the integration of various methods, including magnetic resonance imaging and magnetic resonance-guided neuronavigation systems, is important to perform TUS experiments for precise targeting. We then review the current state of the literature on TUS neuromodulation, with a particular focus on human subjects, targeting both the cerebral cortex and deep subcortical structures. Finally, we outline future perspectives of TUS in clinical applications in psychiatric and neurological fields.

Effects of Transcranial Ultrasound Stimulation on Blood Oxygen Metabolism and Brain Rhythms in Nitroglycerin-Induced Migraine Mice.

OBJECTIVES: In this study, we aimed to investigate the regulatory mechanism of transcranial ultrasound stimulation (TUS) on nitroglycerin-induced migraine in mice. MATERIALS AND METHODS: The experiment was divided into four groups, namely, the normal saline control group (n = 9), ultrasound stimulation control group (n = 6), nitroglycerin-induced migraine group (n = 9), and ultrasound stimulation group (n = 9). The behavior, blood oxygen metabolism, and brain rhythm distribution of the four groups were analyzed. RESULTS: We found that after TUS, the movement time and speed of mice with migraine are modulated to those of the control groups, and the number of head scratching and grooming events is significantly reduced. TUS increased the deoxygenated hemoglobin, and the power of the 4-to-40 Hz frequency band of local field potentials in the cortex of migraine mice. TUS also decreased the expression of plasma calcitonin gene-related peptide and cortical c-Fos protein. CONCLUSIONS: Ultrasound stimulation can regulate brain rhythm and blood oxygen metabolism and reduce migraine symptoms in mice. The regulatory mechanism may be related to reducing calcitonin gene-related peptide in blood vessels.

Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions.

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aß) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aß. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aß plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.

Correlation between Transcranial Ultrasound and CT Head to Detect Clinically Significant Conditions in Post-craniectomy Patients Performed by Emergency Physician: A Pilot Study.

Background: The main objective is to detect clinically significant conditions by transcranial ultrasound (TCS) in post-decompressive craniectomy (DC) patients who come to the emergency department. Materials and methods: This was a cross-sectional observational study. We studied 40 post-DC patients. After primary stabilization, TCS was done. Computer tomography of head was done within 2 hours of performing TCS. The correlation between both modalities were assessed by the measurement of lateral ventricle (LV) (Bland-Altman plot), Midline shift and mass lesion. Additionally, normal cerebral anatomy, 3rd and 4th ventricles and external ventricular drainage (EVD) catheter visualization were also done. Results: About 14/40 patients came with non-neurosurgical complaints and 26/40 patients came with neurosurgical complaints. Patients with non-neurosurgical complaints (4/14) had mass lesions and 1/14 had MLS. Patients with neurosurgical complaints (11/26) had mass lesions and about 5 patients had MLS. A good correlation was found between TCS and CT of head in measuring LV right (CT head = 17.4 ± 13.8 mm and TCS = 17.1 ± 14.8 mm. The mean difference (95% CI) = [0.28 (-1.9 to 1.33), ICC 0.93 (0.88-0.96)], Left [CT head = 17.8 ± 14.4 mm and TCS = 17.1 ± 14.2 mm, the mean difference (95% CI) 0.63 (-1.8 to 0.61), ICC 0.96 (0.93-0.98)], MLS [CT head = 6.16 ± 3.59 (n = 7) and TCS = 7.883 ± 4.17 (n = 6)] and mass lesions (kappa 0.84 [0.72-0.89] [95% CI] p-value < 0.001). The agreement between both modalities for detecting mass lesions is 93.75%. Conclusion: Point of care ultrasound (POCUS) is a bedside, easily operable, non-radiation hazard and dynamic imaging tool that can be used for TCS as a supplement to CT head in post-DC patients in emergency as well as in ICU. However, assessment of the ventricular system (pre/post-EVD insertion), monitoring of regression/progression of mass lesion, etc. can be done with TCS. Repeated scans are possible in less time which can decrease the frequency of CT head. How to cite this article: Chouhan R, Sinha TP, Bhoi S, Kumar A, Agrawal D, Nayer J, et al. Correlation between Transcranial Ultrasound and CT Head to Detect Clinically Significant Conditions in Post-craniectomy Patients Performed by Emergency Physician: A Pilot Study. Indian J Crit Care Med 2024;28(3):299-306.

Transient Cerebral Circulation Arrest in SAH.

How to cite this article: Salhotra R. Transient Cerebral Circulation Arrest in SAH. Indian J Crit Care Med 2024;28(6):620-621.

Role of Transcranial Ultrasound and Doppler Studies to Evaluate Intracranial Pathologies in Preterm and High-risk Term Neonates.

Background: Transcranial grayscale neurosonography (NSG) and Doppler studies have major role in diagnosing neonate intracranial pathologies. The aim of the study is to evaluate the role of NSG and Doppler studies in correlation with clinical hypotonia and seizures in preterm neonates and high-risk term neonates. The prevalence of intracranial pathology is the second aim of this study. Methods: The present cross-sectional study was done in a tertiary care teaching hospital for 2 years. The study population of 120 cases comprised two groups: one group of 60 preterm neonates and the other of 60 high-risk term neonates with a history of well-defined episode of fetal distress. The NSG and Doppler findings (resistance index ≤0.62 is the optimum cutoff point for diagnosing perinatal asphyxia) are recorded. The sensitivity and specificity values for the NSG study alone, the Doppler study alone, and the combined NSG and Doppler studies are calculated. Results: The majority (46%) of preterm neonates had presented with germinal matrix hemorrhage, whereas a majority (46%) of high-risk term neonates had presented with periventricular and subcortical cysts. Comparison of the sensitivity of NSG versus Doppler versus combined NSG and Doppler in evaluating hypotonia and seizures in preterm (P = 0.0442) and high-risk term neonates (P = 0.0399) was significant. Conclusion: NSG combined with the Doppler study has significantly higher sensitivity than NSG alone in both groups. The specificity of the Doppler study is also high in both groups. Thus, it is strongly recommended to include Doppler during every NSG study to increase the detection rate.

Transcranial ultrasound stimulation at the peak-phase of theta-cycles in the hippocampus improve memory performance.

The present study aimed to investigate the effectiveness of closed-loop transcranial ultrasound stimulation (closed-loop TUS) as a non-invasive, high temporal-spatial resolution method for modulating brain function to enhance memory. For this purpose, we applied closed-loop TUS to the CA1 region of the rat hippocampus for 7 consecutive days at different phases of theta cycles. Following the intervention, we evaluated memory performance through behavioral testing and recorded the neural activity. Our results indicated that closed-loop TUS applied at the peak phase of theta cycles significantly improves the memory performance in rats, as evidenced by behavioral testing. Furthermore, we observed that closed-loop TUS modifies the power and cross-frequency coupling strength of local field potentials (LFPs) during memory task, as well as modulates neuronal activity patterns and synaptic transmission, depending on phase of stimulation relative to theta rhythm. We demonstrated that closed-loop TUS can modulate neural activity and memory performance in a phase-dependent manner. Specifically, we observed that effectiveness of closed-loop TUS in regulating neural activity and memory is dependent on the timing of stimulation in relation to different theta phase. The findings implied that closed-loop TUS may have the capability to alter neural activity and memory performance in a phase-sensitive manner, and suggested that the efficacy of closed-loop TUS in modifying neural activity and memory was contingent on timing of stimulation with respect to the theta rhythm. Moreover, the improvement in memory performance after closed-loop TUS was found to be persistent.

Low-intensity transcranial ultrasound stimulation modulates neural activities in mice under propofol anaesthesia.

BACKGROUND: Previous studies have reported that transcranial focused ultrasound stimulation can significantly decrease the time to emergence from intraperitoneal ketamine-xylazine anaesthesia in rats. However, how transcranial focused ultrasound stimulation modulates neural activity in anaesthetized rats is unclear. METHODS: In this study, to answer this question, we used low-intensity transcranial ultrasound stimulation (TUS) to stimulate the brain tissue of propofol-anaesthetized mice, recorded local field potentials (LFPs) in the mouse motor cortex and electromyography (EMG) signals from the mouse neck, and analysed the emergence and recovery time, mean absolute power, relative power and entropy of local field potentials. RESULTS: We found that the time to emergence from anaesthesia in the TUS group (20.3 ± 1.7 min) was significantly less than that in the Sham group (32 ± 2.6 min). We also found that compared with the Sham group, 20 min after low-intensity TUS during recovery from anaesthesia, (1) the absolute power of local field potentials in mice was significantly reduced in the [1-4 Hz] and [13-30 Hz] frequency bands and significantly increased in the [55-100 Hz], [100-140 Hz] and [140-200 Hz] frequency bands; (2) the relative power of local field potentials in mice was enhanced at [30-45 Hz], [100-140 Hz] and [140-200 Hz] frequency bands; (3) the entropy of local field potentials ([1-200 Hz]) was increased. CONCLUSION: These results demonstrate that low-intensity TUS can effectively modulate neural activities in both awake and anaesthetized mice and has a positive effect on recovery from propofol anaesthesia in mice.

Transcranial Ultrasonic Focusing by a Phased Array Based on Micro-CT Images.

In this paper, we utilize micro-computed tomography (micro-CT) to obtain micro-CT images with a resolution of 60 µm and establish a micro-CT model based on the k-wave toolbox, which can visualize the microstructures in trabecular bone, including pores and bone layers. The transcranial ultrasound phased array focusing field characteristics in the micro-CT model are investigated. The ultrasonic waves are multiply scattered in skull and time delays calculations from the transducer to the focusing point are difficult. For this reason, we adopt the pulse compression method and the linear frequency modulation Barker code to compute the time delay and implement phased array focusing in the micro-CT model. It is shown by the simulation results that ultrasonic loss is mainly caused by scattering from the microstructures of the trabecular bone. The ratio of main and side lobes of the cross-correlation calculation is improved by 5.53 dB using the pulse compression method. The focusing quality and the calculation accuracy of time delay are improved. Meanwhile, the beamwidth at the focal point and the sound pressure amplitude decrease with the increase in the signal frequency. Focusing at different depths indicates that the beamwidth broadens with the increase in the focusing depth, and beam deflection focusing maintains good consistency in the focusing effect at a distance of 9 mm from the focal point. This indicates that the phased-array method has good focusing results and focus tunability in deep cranial brain. In addition, the sound pressure at the focal point can be increased by 8.2% through amplitude regulation, thereby enhancing focusing efficiency. The preliminary experiment verification is conducted with an ex vivo skull. It is shown by the experimental results that the phased array focusing method using pulse compression to calculate the time delay can significantly improve the sound field focusing effect and is a very effective transcranial ultrasound focusing method.

Transcranial sonographic measurement of the third ventricle to detect hydrocephalus in children population: Correlation to computed tomography.

BACKGROUND: In neuro-intensive care, transcranial temporal ultrasound is used in adults and children to monitor brain-injured patients. It is accepted as a valuable tool for exploring brain structures. Our study aims to establish a correlation between the measurement of the third ventricle (V3) by transcranial ultrasound via temporal window and a reference method, computed tomography (CT), which could validate the method for hydrocephalus detection in the children population. DESIGN: This is a prospective double-blind study of 34 children under 15 years. Two consultants in intensive care performed the ultrasound while a radiologist performed the CT measurements. RESULTS: Of the 34 patients included, the V3 could be measured in 88% of cases. Among these 30 patients, there is a good correlation between CT and ultrasound measurements with a Spearman correlation coefficient of 0.773. This correlation is more important as the diameter of the V3 increases. We could determine a threshold of 3.65 mm in diameter to identify hydrocephalus on ultrasound with a detection sensitivity of 100%, and a specificity of 94.1%. CONCLUSION: Measuring the diameter of the V3 by trans-cranial sonography remains a simple, reproducible, non-invasive tool and has a good correlation with reference examinations such as CT.

[Modulation of motor responses and neural activities with transcranial ultrasound stimulation based on closed-loop control].

Closed-loop transcranial ultrasound stimulation technology is based on real-time feedback signals, and has the potential for precise regulation of neural activity. In this paper, firstly the local field potential (LFP) and electromyogram (EMG) signals of mice under different intensities of ultrasound stimulation were recorded, then the mathematical model of ultrasound intensity and mouse LFP peak/EMG mean was established offline based on the data, and the closed-loop control system of LFP peak and EMG mean based on PID neural network control algorithm was simulated and built to realize closed-loop control of LFP peak and EMG mean of mice. In addition, using the generalized minimum variance control algorithm, the closed-loop control of theta oscillation power was realized. There was no significant difference between the LFP peak, EMG mean and theta power under closed-loop ultrasound control and the given value, indicating a significant control effect on the LFP peak, EMG mean and theta power of mice. Transcranial ultrasound stimulation based on closed-loop control algorithms provides a direct tool for precise modulation of electrophysiological signals in mice.