Transcranial Application Research Articles

A Comparative Feasibility Study for Transcranial Extracorporeal Shock Wave Therapy.

The potential beneficial regenerative and stimulatory extracorporeal shock wave therapy (ESWT) applications to the central nervous system have garnered interest in recent years. Treatment zones for these indications are acoustically shielded by bones, which heavily impact generated sound fields. We present the results of high-resolution tissue-realistic simulations, comparing the viability of different ESWT applicators in their use for transcranial applications. The performances of electrohydraulic, electromagnetic, and piezoelectric transducers for key reflector geometries are compared. Based on density information obtained from CT imaging of the head, we utilized the non-linear wave propagation toolset Matlab k-Wave to obtain spatial therapeutic sound field geometries and waveforms. In order to understand the reliability of results on the appropriate modeling of the skull, three different bone attenuation models were compared. We find that all currently clinically ESWT applicator technologies show significant retention of peak pressures and energies past the bone barrier. Electromagnetic transducers maintain a significantly higher energy flux density compared to other technologies while low focusing strength piezoelectric applicators have the weakest transmissions. Attenuation estimates provide insights into sound field degradation and energy losses, indicating that effective transcranial therapies can readily be attained with current applicators. Furthermore, the presented approach will allow for future targeted in silico development and the design of applicators and therapy plans to ultimately improve therapeutic outcomes.

Numerical Analysis of Transcranial Magnetic Stimulation Application in Patients With Orofacial Pain.

In this paper, we monitored the accuracy of non-navigated application of repetitive Transcranial Magnetic Stimulation (rTMS) in 10 patients suffering from orofacial pain by using functional magnetic resonance (fMRI), computer modeling and numerical simulation. Through a unique process, each fMRI scan was used to define a Region of Interest (ROI) where the source of the orofacial pain was located, which was to be stimulated using rTMS. For each patient, MRI scans with a spatial resolution of 0.7 mm were converted into an anatomically accurate head model. The head model including the ROI was then co-registered with a model of the stimulation coil in an electromagnetic field numerical simulator. The accuracy of rTMS application was evaluated based on the calculations of electric field intensity distribution in the ROI. The research has yielded unique insight into ROIs (with average volume 904 mm3) in patients with orofacial pain and has also extended further possibilities of human head MRI image semi-automatic segmentation. According to the calculations performed, the average ROI volume that was stimulated by an electric field with an intensity of over 80 V/m was only 4.4%, with the maximum ROI volume being 20.5%. Furthermore, a numerical study of the impact of coil rotation and translation was performed. It demonstrated a) the optimal placement of the stimulation coil can significantly increase the volume of the stimulated ROI up to 60% and b) patients with orofacial pain would need precise coil positioning with a navigation error lower than 10 mm. Due to an acceptable proccessing time of up to 6 hours, described numerical simulation opens up new options for precise rTMS treatment planning. This planning platform together with patient-specific navigated rTMS, could lead to significant increase of treatment outcomes in patients suffering from orofacial pain.

Focused Ultrasound-Mediated Intranasal Brain Drug Delivery Technique (FUSIN).

The blood-brain barrier (BBB) is the major barrier for brain drug delivery and limits the treatment options for central nervous system diseases. To circumvent the BBB, we introduced the focused ultrasound-mediated intranasal brain drug delivery (FUSIN) technique. FUSIN utilizes the nasal route for direct nose-to-brain drug administration, bypassing the BBB and minimizing systemic exposure. It also uses the transcranial application of ultrasound energy focused at a targeted brain region to induce microbubble cavitation, which enhances the transport of intranasally administered agents at the FUS-targeted brain location. FUSIN is unique in that it can achieve noninvasive and localized brain drug delivery with minimized systemic toxicity. The goal of this chapter is to provide a detailed protocol for FUSIN delivery to the mouse brain.

The use of magnetic therapy in the treatment and medical rehabilitation of atopic dermatitis in children and adolescents

An urgent aspect of scientific research in atopic dermatitis is the development of new complex methods of pathogenetic and symptomatic therapy and alternative treatment options that can effectively relieve exacerbations of the disease and prolong remission between them. As a therapeutic physical factor, magnetotherapy has long been successfully used in medical practice. Promising medical technologies include transcranial application of a traveling variable magnetic field, local low-frequency magnetotherapy, and magnetophoresis. The main tasks of rehabilitation and treatment are aimed at normalizing the state of all organs, the central and autonomic nervous system of the patient, reducing hypersensitivity and itching of atopic skin, as well as normalizing sleep and relieving psycho-emotional stress.

Fast acquisition of resting motor threshold with a stimulus–response curve – Possibility or hazard for transcranial magnetic stimulation applications?

ObjectivePrevious research has suggested that transcranial magnetic stimulation (TMS) related cortical excitability measures could be estimated quickly using stimulus–response curves with short interstimulus intervals (ISIs). Here we evaluated the resting motor threshold (rMT) estimated with these curves. MethodsStimulus-response curves were measured with three ISIs: 1.2–2 s, 2–3 s, and 3–4 s. Each curve was formed with 108 stimuli using stimulation intensities ranging from 0.75 to 1.25 times the rMTguess, which was estimated based on motor evoked potential (MEP) amplitudes of three scout responses. ResultsThe ISI did not affect the rMT estimated from the curves (F = 0.235, p = 0.683) or single-trial MEP amplitudes at the group level (F = 0.90, p = 0.405), but a significant subject by ISI interaction (F = 3.64; p < 0.001) was detected in MEP amplitudes. No trend was observed which ISI was most excitable, as it varied between subjects. ConclusionsAt the group level, the stimulus–response curves are unaffected by the short ISI. At the individual level, these curves are highly affected by the ISI. SignificanceEstimating rMT using stimulus–response curves with short ISIs impacts the rMT estimate and should be avoided in clinical and research TMS applications.

Transcranial focused ultrasound modulates cortical and thalamic motor activity in awake sheep

Transcranial application of pulsed low-intensity focused ultrasound (FUS) modulates the excitability of region-specific brain areas, and anesthetic confounders on brain activity warrant the evaluation of the technique in awake animals. We examined the neuromodulatory effects of FUS in unanesthetized sheep by developing a custom-fit headgear capable of reproducibly placing an acoustic focus on the unilateral motor cortex (M1) and corresponding thalamic area. The efferent responses to sonication, based on the acoustic parameters previously identified in anesthetized sheep, were measured using electromyography (EMG) from both hind limbs across three experimental conditions: on-target sonication, off-target sonication, and without sonication. Excitatory sonication yielded greater amplitude of EMG signals obtained from the hind limb contralateral to sonication than that from the ipsilateral limb. Spurious appearance of motion-related EMG signals limited the amount of analyzed data (~ 10% selection of acquired data) during excitatory sonication, and the averaged EMG response rates elicited by the M1 and thalamic stimulations were 7.5 ± 1.4% and 6.7 ± 1.5%, respectively. Suppressive sonication, while sheep walked on the treadmill, temporarily reduced the EMG amplitude from the limb contralateral to sonication. No significant change was found in the EMG amplitudes during the off-target sonication. Behavioral observation throughout the study and histological analysis showed no sign of brain tissue damage caused by the acoustic stimulation. Marginal response rates observed during excitatory sonication call for technical refinement to reduce motion artifacts during EMG acquisitions as well as acoustic aberration correction schemes to improve spatial accuracy of sonication. Yet, our results indicate that low-intensity FUS modulated the excitability of regional brain tissues reversibly and safely in awake sheep, supporting its potential in theragnostic applications.

Optimization of Complex Sanatorium-resort Treatment for Patients with Chronic Insomnia by Including Transcranial Magnetic Therapy

Aim. To determine the effectiveness of the transcranial magnetic therapy course inclusion in the sanatorium-resort treatment complex for patients with chronic insomnia. Material and methods. 122 patients with a verified diagnosis of chronic insomnia were examined, the average age was 54.0±0.92 years, of which 68.9% were women and 31.1% were men. The patients were divided into 2 randomized groups: 62 in the main group (who received health resort treatment complex and transcranial magnetic therapy) and 60 in the comparison group (an identical complex without transcranial magnetic therapy). All patients were evaluated for the index of insomnia severity, symptoms of impaired daytime functioning, daytime sleepiness on the Epworth scale, anxiety and depression on the HADS scale, vegetative tone, polysomnography data, and quality of life (SF-36). Results. As a result of the course of treatment, the average index of insomnia severity in the main group decreased from 20.3±0.32 to 13.0±0.38 (p&lt;0.001), in the comparison group from 19.9±0.32 to 15.3±0.29 (p&lt;0.001). Clinically, in addition to improving sleep quality, patients reported improved daytime functioning significantly more pronounced in the main group for most of the analyzed symptoms (p&lt;0.05). A comparative analysis of the daytime sleepiness results assessment on the Epworth scale, anxiety and depression on the HADS scale before and after treatment showed a statistically significant positive trend more pronounced in the main group (p&lt;0.05). The change in the indicators of vegetative tone in patients with chronic insomnia after treatment was expressed in a statistically significant decrease in the number of patients with sympathicotonia by 15.7% (p&lt;0.05) and an increase in the number of patients with normotonic vegetative support by 17.4% (p&lt;0.05). In the comparison group, the results were significantly worse (p&lt;0.05). After the use of therapeutic complexes, there was a favorable reliable dynamic in the change in polysomnography indicators in patients of both groups, however, the positive result in the main group was more pronounced (p&lt;0.05). the resulting positive assessment of the transcranial magnetotherapy application was a statistically significant improvement in the quality of life of patients in the main group (p&lt;0.05). Conclusion. The inclusion of transcranial magnetotherapy in complex health resort treatment treatment can significantly improve the effectiveness of sleep disorders treatment and improve the quality of life of patients with chronic insomnia.

Terahertz modulated infrared radiation in the complex treatment of patients in the acute period of ischemic stroke

The rationale for the use of infrared (IR) radiation with terahertz (THz) modulation in the complex treatment of patients in the acute period of IS. The results of transcranial application of IR radiation with THz modulation in 112 patients in the acute period of IS are presented. In the main group (38 patients) the infrared radiation with THz modulation was used on the projection of the IS focus in addition to basic drug therapy; in the control group (37 patients) - basic drug therapy; in the placebo group (37 patients) the physiotherapy was mimicked. The data of neurological status and neuro-functional indicators were assessed using the NIHSS, MMSE, Rankin, and Rivermid scales. Cerebral blood flow was examined using duplex scanning of brachiocephalic vessels. The inclusion in the complex treatment of IR radiation with THz modulation on the projection of the IS focus in the acute period contributed to a significant regression of neurological deficit, a complete recovery of cognitive functions and an increase in daily activity due to the restoration of adequate blood supply on the side of the affected hemisphere. A pathogenesis justified method of treating acute IS is proposed which can increase the effectiveness of early neurorehabilitation measures. An early improvement in cerebral hemoperfusion led to the creation of optimal conditions for the survival of neural structures and the preservation of their functional activity that demonstrated the neuroprotective feasibility of early inclusion of IR radiation with THz modulation in the complex treatment of patients in the acute period of IS.

Diagnostic capabilities of transcranial magnetic stimulation to predict motor recovery after a stroke

Transcranial magnetic stimulation is a method of focal non-invasive brain stimulation, characterized by high spatial and temporal resolution. To date, diagnostic transcranial magnetic stimulation has been used in clinical practice primarily to assess an involvement of the upper motor neurons and to measure the velocity of the neuronal impulse propagation. However, in the last 10 years, a possible range of transcranial magnetic stimulation diagnostic applications has significantly expanded. Many transcranial magnetic stimulation approaches are coming from scientific laboratories to clinical practice due to an increased availability of transcranial magnetic stimulation equipment, in particular, magnetic resonance imaging navigation for transcranial magnetic stimulation and a combination of the transcranial magnetic stimulation with electroencephalography and also due to an increased awareness of the clinicians. The diagnostic potential of transcranial magnetic stimulation in relation to motor recovery after a stroke can be classified into 4 directions:1) assessment of the vertical tracts integrity (primarily, the cortico-spinal tract); 2) an assessment of the cortical excitation-inhibition balance;3) probing of the functional and effective connectivity among brain regions (primarily, cortical convexity and cerebellum);4) motor mapping to evaluate cortical reorganization.In this article we will present these 4 directions of the transcranial magnetic stimulation application to study motor system pathophysiology and to predict motor outcome in stroke, including both existing and developing approaches.

Electromagnetic Field Therapy: A Rehabilitative Perspective in the Management of Musculoskeletal Pain - A Systematic Review.

Electromagnetic fields (EMFs) provide a non-invasive, safe, and easy method to treat pain with respect to musculoskeletal diseases. The purpose of this systematic review was to describe the use of electromagnetic therapy in the rehabilitation field by investigating the efficacy in acute and chronic pain in the musculoskeletal disorders. A database search was conducted using the following resources: PubMed, Cochrane, PEDro, SCOPUS, and WoS. The following MESH terms were used: [Electromagnetic field AND/OR Rehabilitation], [Electromagnetic field AND/OR Pain], [Pulsed Magnetic field AND/OR Rehabilitation] and [Pulsed Magnetic field AND/OR Pain], [Pulsed Electromagnetic field AND/OR Rehabilitation] and [Pulsed Electromagnetic field AND/OR Pain], per the guidelines of the PRISMA statement. Articles published between January 1, 2009 and December 31, 2018 were included as assessment of musculoskeletal pain conditions, randomized clinical trial including crossover and prospective design studies, full English text available, population age > 18 years; instead were excluded neurological randomized clinical trials, transcranial magnetic stimulation application, neuropathic pain, animal/in vitro studies, and articles without English abstract or English full text. Three independent investigators (AMC, NG, and LP) retrieved all the information. Twenty-one RTC (N=21) were considered for the inclusion and exclusion criteria. The results showed as pulsed magnetic fields at low intensity and frequency (from 1 Hz up to 100 Hz) are commonly used with efficacy in resolving musculoskeletal pain. EMFs therapy is a well tolerated, effective with no negative side effects, which can be integrated with rehabilitation for the treatment of chronic and acute pain in musculoskeletal diseases, but further studies are needed to examine the use of more standardized protocols.

Regulation and Ethics of Transcranial Electrical Stimulation: A General View

Transcranial application of low-intensity electrical stimuli is a non-invasive brain stimulation procedure, which allows one to alter the excitability of cortical cells in both humans and animals. There is a broad consensus regarding the safety of this approach in humans, and different versions and protocols of this technique have been used in basic research and clinical studies for years. In this review, we aim to provide updated information on regulatory and ethical issues concerning the use of different versions of transcranial electrical stimulation (tES). This information may be critical due to its implications on the welfare and health of patients. Although tES is a safe and effective method with potential clinical and research utilities, the legal regulation criteria concerning the use different versions of tES are of critical relevance due to implications of brain stimulation for human health and well-being. Recent publications that review and describe all regulatory and safety aspects regarding the use of tES offer a practical vision about the most up-to-date information in this field and more relevant ethical implications.

Effects of transcranial direct current stimulation on heart rate variability: a systematic review protocol.

This systematic review aims to synthesize the available evidence on the effects of transcranial direct current stimulation on heart rate modulation, indexed by heart rate variability parameters in healthy individuals and those with clinical disorders. There is some evidence that altered heart rate variability parameters are associated with different clinical disorders. For example, diminished parasympathetic activity has been explored as a potential biomarker for some chronic pain conditions. Considering the dynamic interaction between brain and heart, neuromodulatory strategies targeting this relationship could exert a positive influence on the cardiac autonomic system. Transcranial direct current stimulation is a non-invasive neuromodulation technique that has been presenting recent advances in the treatment of various clinical disorders. However, the evidence concerning transcranial direct current stimulation application focusing on brain-heart interaction is still controversial. This review will consider studies that investigate the effects of transcranial direct current stimulation on heart rate variability in healthy participants or those with clinical disorders. This review will follow JBI systematic review methodology recommendations. PubMed, Embase, CINAHL, Web of Science, PsycNET, Cochrane Controlled Register of Trials (CENTRAL) and Physiotherapy Evidence Database (PEDro) will be searched, along with several sources of gray literature. Retrieval of full-text studies, and assessment of methodological quality and data extraction, will be performed independently by two reviewers. Data will be pooled in statistical meta-analysis, where possible. PROSPERO CRD42018114105.

Considerations for ultrasound exposure during transcranial MR acoustic radiation force imaging

The aim of this study was to improve the sensitivity of magnetic resonance-acoustic radiation force imaging (MR-ARFI) to minimize pressures required to localize focused ultrasound (FUS) beams, and to establish safe FUS localization parameters for ongoing ultrasound neuromodulation experiments in living non-human primates. We developed an optical tracking method to ensure that the MR-ARFI motion-encoding gradients (MEGs) were aligned with a single-element FUS transducer and that the imaged slice was prescribed at the optically tracked location of the acoustic focus. This method was validated in phantoms, which showed that MR-ARFI-derived displacement sensitivity is maximized when the MR-ARFI MEGs were maximally aligned with the FUS propagation direction. The method was then applied in vivo to acquire displacement images in two healthy macaque monkeys (M fascicularis) which showed the FUS beam within the brain. Temperature images were acquired using MR thermometry to provide an estimate of in vivo brain temperature changes during MR-ARFI, and pressure and thermal simulations of the acoustic pulses were performed using the k-Wave package which showed no significant heating at the focus of the FUS beam. The methods presented here will benefit the multitude of transcranial FUS applications as well as future human applications.

A Study of Biomagnetic Stimulation for Transcranial Application

Biomagnetic stimulation is a treatment uses the application of magnetic field principle for a therapeutic purpose. This non-invasive therapeutic technique use low frequency electromagnetic field which is less than 10 MHz. In transcranial application, electromagnetic field is use to stimulate the brain tissue for the people affected by weaken neurologic and psychiatric disorders. This paper discusses the modelling and simulation of Transcranial Magnetic Stimulation using Comsol Multiphysics software. In this research four designs have been simulated. The overall analysis indicates that a single coil design has the best performance in stimulating the area of interest at the frequency of 5MHz.

MRI monitoring of temperature and displacement for transcranial focus ultrasound applications

BackgroundTranscranial focus ultrasound applications applied under MRI-guidance benefit from unrivaled monitoring capabilities, allowing the recording of real-time anatomical information and biomarkers like the temperature rise and/or displacement induced by the acoustic radiation force. Having both of these measurements could allow for better targeting of brain structures, with improved therapy monitoring and safety. MethodWe investigated the use of a novel MRI-pulse sequence described previously in Bour et al., (2017) to quantify both the displacement and temperature changes under various ultrasound sonication conditions and in different regions of the brain. The method was evaluated in vivo in a non-human primate under anesthesia using a single-element transducer (f = 850 kHz) in a setting that could mimic clinical applications. Acquisition was performed at 3 T on a clinical imaging system using a modified single-shot gradient echo EPI sequence integrating a bipolar motion-sensitive encoding gradient. Four slices were acquired sequentially perpendicularly or axially to the direction of the ultrasound beam with a 1-Hz update frequency and an isotropic spatial resolution of 2-mm. A total of twenty-four acquisitions were performed in three different sets of experiments. Measurement uncertainty of the sequence was investigated under different acoustic power deposition and in different regions of the brain. Acoustic simulation and thermal modeling were performed and compared to experimental data. ResultsThe sequence simultaneously provides relevant information about the focal spot location and visualization of heating of brain structures: 1) The sequence localized the acoustic focus both along as well as perpendicular to the ultrasound direction. Tissue displacements ranged from 1 to 2 μm. 2) Thermal rise was only observed at the vicinity of the skull. Temperature increase ranged between 1 and 2 °C and was observed delayed relative the sonication due to thermal diffusion. 3) The fast frame rate imaging was able to highlight magnetic susceptibility artifacts related to breathing, for the most caudal slices. We demonstrated that respiratory triggering successfully restored the sensitivity of the method (from 0.7 μm to 0.2 μm). 4) These results were corroborated by acoustic simulations. ConclusionsThe current rapid, multi-slice acquisition and real-time implementation of temperature and displacement visualization may be useful in clinical practices. It may help defining operational safety margins, improving therapy precision and efficacy. Simulations were in good agreement with experimental data and may thus be used prior treatment for procedure planning.

Accurate anatomical head segmentations: a data set for biomedical simulations.

Detailed computational anatomical models of the entire head are needed for accurate in silico modeling in a variety of transcranial stimulation applications. Models from different subjects help to understand and account for population variability. To this end, we have developed a new library of head models of 20 individuals, segmented from co-aligned multi-modal medical image data. The acquired image modalities allow to accurately model tissues with different material properties, such as electrical conductivity or spatially varying acoustic properties. The usefulness of the models is illustrated for two example applications.

Localized Blood–Brain Barrier Opening in Ovine Model Using Image-Guided Transcranial Focused Ultrasound

Transcranial application of focused ultrasound (FUS) combined with vascular introduction of microbubble contrast agents (MBs) has emerged as a non-invasive technique that can temporarily create a localized opening in the blood–brain barrier (BBB). Under image-guidance, we administered FUS to sheep brain after intravenous injection of microbubbles. BBB opening was confirmed by performing dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to detect the extravasated gadolinium-based magnetic resonance contrast agents. Through pharmacokinetic analysis as well as independent component analysis of the DCE-MRI data, we observed localized enhancement in BBB permeability at the area that subjected to acoustic pressure of 0.48 MPa (mechanical index = 0.96). On the other hand, application of a higher pressure at 0.58 MPa resulted in localized, minor cerebral hemorrhage. No animals exhibited abnormal behavior during the post-FUS survival periods up to 2 mo. Our data suggest that monitoring for excessive BBB disruption is important for safe translation of the method to humans.

Iterative image reconstruction algorithm for transcranial photoacoustic tomography applications

Iterative image reconstruction algorithm for transcranial photoacoustic tomography applications

Monitoring of acute stroke patients with suppressed consciousness by using transcranial Doppler sonography

Introduction: Dynamic monitoring of the patients presenting with suppressed consciousness during the acute stage of stroke plays an important role in the diagnostic and therapeutic process as a whole. Aim: The objective of the present study was to analyze the initial results from the twofold transcranial Doppler sonography application in acute stroke patients with suppressed consciousness aiming at optimizing their timely treatment. Materials and Methods: The histories of 46 patients, 21 males and 25 females, at a mean age of 75 years with acute stroke and a different degree of suppressed consciousness hospitalized during the period from January 1, 2018 to January 31, 2019 were analyzed. All the patients were examined by means of transcranial Doppler sonography. The degree of suppressed consciousness was evaluated by means of Glasgow-Liege Coma Scale. Results: Thirty-four patients presented with acute ischemic stroke and 12 ones with acute hemorrhagic one. Several accompanying cardiovascular diseases that aggravated the course of the acute cerebrovascular accident were diagnosed. Considerable differences in terms of the mean values according to the Glasgow-Liege Coma Scale were observed. The intervals of the maximal, minimal and average sonographic parameters of four cerebral arteries such as left and right middle cerebral artery and left and right vertebral artery varied within broad limits, too. Conclusion: The application of a constellation of various neuroimaging methods in the patients with acute cerebrovascular diseases could identify essential relationships between the parameters analyzed and risk factors as well as to give assistance to the individualized therapeutic approach.

A Critical Review and Synthesis of Clinical and Neurocognitive Effects of Noninvasive Neuromodulation Antidepressant Therapies.

There is a plethora of current and emerging antidepressant therapies in the psychiatric armamentarium for the treatment of major depressive disorder. Noninvasive neuromodulation therapies are one such therapeutic category; they typically involve the transcranial application of electrical or magnetic stimulation to modulate cortical and subcortical brain activity. Although electroconvulsive therapy (ECT) has been used since the 1930s, with the prevalence of major depressive disorder and treatment-resistant depression (TRD), the past three decades have seen a proliferation of noninvasive neuromodulation antidepressant therapeutic development. The purpose of this critical review was to synthesize information regarding the clinical effects, neurocognitive effects, and possible mechanisms of action of noninvasive neuromodulation therapies, including ECT, transcranial magnetic stimulation, magnetic seizure therapy, and transcranial direct current stimulation. Considerable research has provided substantial information regarding their antidepressant and neurocognitive effects, but their mechanisms of action remain unknown. Although the four therapies vary in how they modulate neurocircuitry and their resultant antidepressant and neurocognitive effects, they are nonetheless useful for patients with acute and chronic major depressive disorder and TRD. Continued research is warranted to inform dosimetry, algorithm for administration, and integration among the noninvasive neuromodulation therapies and with other antidepressant strategies to continue to maximize their safety and antidepressant benefit.