Transcranial focused ultrasound stimulation reduces vasogenic edema after middle cerebral artery occlusion in mice

Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.

Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβplaques and brain rhythms in 5×FAD mice

Background:Alzheimer's disease(AD)is the most common cause of dementia,and is characterized by amyloid-β(Aβ)plaques and tauopathy.Reducing Aβhas been considered a major AD treatment strategy in pharmacological and non-pharmacological approaches.Impairment of gamma oscillations,which play an important role in perception and cognitive function,has been shown in mouse AD models and human patients.Recently,the therapeutic effect of gamma entrainment in AD mouse models has been reported.Given that ultrasound is an emerging neuromodulation modality,we investigated the effect of ultrasound stimulation pulsed at gamma frequency(40 Hz)in an AD mouse model.Methods:We implanted electroencephalogram(EEG)electrodes and a piezo-ceramic disc ultrasound transducer on the skull surface of 6-month-old 5×FAD and wild-type control mice(n=12 and 6,respectively).Six 5×FAD mice were treated with two-hour ultrasound stimulation at 40 Hz daily for two weeks,and the other six mice received sham treatment.Soluble and insoluble Aβlevels in the brain were measured by enzyme-linked immunosorbent assay.Spontaneous EEG gamma power was computed by wavelet analysis,and the brain connectivity was examined with phase-locking value and cross-frequency phase-amplitude coupling.Results:We found that the total Aβ42 levels,especially insoluble Aβ42;in the treatment group decreased in pre-and infra-limbic cortex(PIL)compared to that of the sham treatment group.A reduction in the number of Aβplaques was also observed in the hippocampus.There was no increase in microbleeding in the transcranial ultrasound stimulation(tUS)group.In addition,the length and number of microglial processes decreased in PIL and hippocampus.Encel-phalographic spontaneous gamma power was increased,and cross-frequency coupling was normalized,implying functional improvement after tUS stimulation.Conclusion:These results suggest that the transcranial ultrasound-based gamma-band entrainment technique can be an effective therapy for AD by reducing the Aβload and improving brain connectivity.

Evaluation of Prognosis of Brain Function with Early Transcranial Color Doppler Ultrasound in Patients after Cardiopulmonary Resuscitation

Objective: To evaluate the clinical value of transcranial color Doppler ultrasound (TCCD) in assessing cerebral function after cardiopulmonary resuscitation (CPR). Methods: A prospective study was conducted in 52 patients with cardiac arrest treated by CPR from January 2018 to January 2020, and its clinical data were analyzed. According to classification of cerebral performance category (CPC), 31 cases (CPC grade 1 - 2) were selected in the good prognosis group and 21 cases (CPC grade 3 - 5) in the poor prognosis group. The cerebral blood flow was measured by transcranial Doppler ultrasound (TCCD) 24 h after CPR, and the differences were compared between the two groups in stroke index, diastolic blood flow velocity (Vd), systolic peak blood flow velocity (Vs) and mean peak blood flow velocity (Vm). The ROC curve of cerebral blood flow after CPR was drawn to predict the prognosis of brain function. Results: The data showed that the pulsatility index of middle cerebral artery of the poor prognosis group decreased within 24 h;the difference between the two groups was statistically significant (p < 0.05);the Vd, Vs, Vm increased in the good prognosis group;the difference between the two groups was statistically significant (p < 0.05). The ROC curve of cerebral blood flow after CPR was drawn to predict the prognosis of brain function, and the results showed that the area under the curve and the optimal critical value of cerebral blood flow were 0.731 and 5.69. The sensitivity and specificity were 67.3% and 79.1% respectively. Conclusion: The cerebral blood flow increase in the early stage of successful CPR is positively correlated with the prognosis of cerebral functional resuscitation. Monitoring intracranial blood flow after CPR by TCCD has clinical value to evaluate prognosis of brain function.

Influence of mode conversions in the skull on transcranial focused ultrasound and temperature fields utilizing the wave field separation method： A numerical study

Transcranial focused ultrasound is a booming noninvasive therapy for brain stimuli. The Kelvin–Voigt equations are employed to calculate the sound field created by focusing a 256-element planar phased array through a monkey skull with the time-reversal method. Mode conversions between compressional and shear waves exist in the skull. Therefore, the wave field separation method is introduced to calculate the contributions of the two waves to the acoustic intensity and the heat source, respectively. The Pennes equation is used to depict the temperature field induced by ultrasound. Five computational models with the same incident angle of 0？and different distances from the focus for the skull and three computational models at different incident angles and the same distance from the focus for the skull are studied. Numerical results indicate that for all computational models, the acoustic intensity at the focus with mode conversions is 12.05%less than that without mode conversions on average. For the temperature rise, this percentage is 12.02%. Besides, an underestimation of both the acoustic intensity and the temperature rise in the skull tends to occur if mode conversions are ignored. However, if the incident angle exceeds 30？, the rules of the over-and under-estimation may be reversed. Moreover,shear waves contribute 20.54% of the acoustic intensity and 20.74% of the temperature rise in the skull on average for all computational models. The percentage of the temperature rise in the skull from shear waves declines with the increase of the duration of the ultrasound.

Therapeutic potential of neuromodulation for demyelinating diseases

Neuromodulation represents a cutting edge class of both invasive and non-invasive therapeutic methods which alter the activity of neurons.Currently,several different techniques have been developed-or are currently being investigated–to treat a wide variety of neurological and neuropsychiatric disorders.Recently,in vivo and in vitro studies have revealed that neuromodulation can also induce myelination,meaning that it could hold potential as a therapy for various demyelinating diseases including multiple sclerosis and progressive multifocal leukencepalopathy.These findings come on the heels of a paradigm shift in the view of myelin's role within the nervous system from a static structure to an active co-regulator of central nervous system plasticity and participant in neuron-mediated modulation.In the present review,we highlight several of the recent findings regarding the role of neural activity in altering myelination including several soluble and contact-dependent factors that seem to mediate neural activitydependent myelination.We also highlight several considerations for neuromodulatory techniques,including the need for further research into spatiotemporal precision,dosage,and the safety and efficacy of transcranial focused ultrasound stimulation,an emerging neuromodulation technology.As the field of neuromodulation continues to evolve,it could potentially bring forth methods for the treatment of demyelinating diseases,and as such,further investigation into the mechanisms of neuron-dependent myelination as well as neuro-imaging modalities that can monitor myelination activity is warranted.

Cognitive Functional Impairment and Hemodynamic Changes in Patients with Symptomatic Leukoaraiosis

Objective: The pathogenesis of leukoaraiosis is still unclear. Many studies have determined that changes in the hemodynamics associated with leukoaraiosis, impaired cerebrovascular reserve, and intracranial hypoperfusion can lead to various clinical manifestations such as motor or cognitive impairment. The purpose of this study was to investigate the relationship between cognitive functional changes and imaging characteristics in patients with symptomatic leukoaraiosis, and to observe the corresponding changes in hemodynamics. Methods: A total of 203 Han patients (aged 43 - 93 years) with symptomatic leukoaraiosis were included in this study. Head magnetic resonance imaging was semi-quantified according to the Fazekas grading standard. Then, each patient was evaluated in terms of cognitive (Montreal scale) and executive function (trail-making test A [TMTA] and TMTB). Specifically, the TMTA asks patients to connect points on a piece of paper numbered from 1 to 25 in order and the TMTB asks patients to arrange numbers and letters in alternating order. In the current work, revised versions of these tests used are to include numbers in square and circular shapes where the shapes needed to be arranged in alternating order. The time required to complete the TMTA and TMTB was recorded. The changes in the blood flow velocity of the middle cerebral artery were also observed using routine Transcranial Doppler ultrasound and the breath-holding test. The dynamic curves of blood flow velocity during the breath-holding test were examined. Results: The cognitive and executive functions of patients with leukoaraiosis are related to the classification of image-based disease characteristics. In this sense, the more serious the leukoaraiosis is, the larger the impairment of cognitive and executive function is. According to the breath-holding test, the peak pattern of the blood flow velocity in the middle cerebral artery was significantly different between the various grades of leukoaraiosis. The peak type of Fazekas grade 0 and I was in the same direction, while the peak type of Fazekas grade II and III was significantly opposed (both p Conclusions: The impairment of cognitive and executive functions in patients with leukoaraiosis correlates with the severity of image-based disease manifestations, which are generally depicted as intracranial hypoperfusion.

Clinical Observation on Acupuncture for Migraine

Objective： To observe the clinical efficacy of acupuncture treatment for migraine. Methods： Forty cases were randomly allocated to a treatment group and a control group, 20 cases in each group. Cases in the treatment group were treated with acupuncture, while cases in the control group were treated with oral Sibelium. After that, the changes of cerebral blood flow were observed before and after treatment. Results： There was significant difference in clinical efficacies between two groups （P〈0.05）. There were also significant differences in arterial blood flow velocities of before and after treatment. Acupuncture can produce substantial differences （P〈0.05） in blood flow velocities of vertebral artery （VA）, middle cerebral artery （MCA） and anterior cerebral artery （ACA） during an increased flow rate. It can also produce statistical differences in blood flow velocities of VA during a decreased flow rate （P〈0.05）. Conclusion： Acupuncture can effectively alleviate the pain of migraine sufferers and exert a two-way regulation on the cerebral blood flow.

Complex Frequency Features for TCD Signal Analysis

In this paper, we report on using pattern recognition techniques for embolic signal(ES) detection based on transcranial doppler ultrasound(TCD) audio data collected via machine EMS-9(from Shenzhen Delicate Electronics, Co. Ltd).Firstly, we adopted complex discrete fourier transform to get spectra of audio recordings; secondly, we used principal component analysis(PCA) for the visualization of selected signals, which makes it easy and intuitive to verify whether a signal contains an embolic component; finally we designed the classifier with support vector machines(SVM) for detection. With contrast to traditional methods of ES detection systems, the proposed approach considers two channel signals from the audio data collected by single transducer, and there is no predefined features for classification. The primary experimental results on real data are promising.