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Abstract Background Aducanumab (Adu), which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid, has been reported to reduce amyloid pathology and improve impaired cognition after administration of a high dose (10 mg/kg) of the drug in Alzheimer’s disease (AD) clinical trials. The purpose of this study was to investigate the effects of a lower dose of Adu (3 mg/kg) with enhanced delivery via focused ultrasound (FUS) in an AD mouse model. Methods The FUS with microbubbles opened the blood–brain barrier (BBB) of the hippocampus for the delivery of Adu. The combined therapy of FUS and Adu was performed three times in total and each treatment was performed biweekly. Y-maze test, Brdu labeling, and immunohistochemical experimental methods were employed in this study. In addition, RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental animals. Results The FUS-mediated BBB opening markedly increased the delivery of Adu into the brain by approximately 8.1 times in the brains. The combined treatment induced significantly less cognitive decline and decreased the level of amyloid plaques in the hippocampi of the 5×FAD mice compared with Adu or FUS alone. Combined treatment with FUS and Adu activated phagocytic microglia and increased the number of astrocytes associated with amyloid plaques in the hippocampi of 5×FAD mice. Furthermore, RNA sequencing identified that 4 enriched canonical pathways including phagosome formation, neuroinflammation signaling, CREB signaling and reelin signaling were altered in the hippocami of 5×FAD mice receiving the combined treatment. Conclusion In conclusion, the enhanced delivery of a low dose of Adu (3 mg/kg) via FUS decreases amyloid deposits and attenuates cognitive function deficits. FUS-mediated BBB opening increases adult hippocampal neurogenesis as well as drug delivery. We present an AD treatment strategy through the synergistic effect of the combined therapy of FUS and Adu.

Abstract Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a risk factor for peritumoral edema (PTE) when gamma knife radiosurgery (GKRS) is performed in patients with meningioma. In addition, we propose the concept of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. This retrospective study included 127 patients who underwent GKRS for convexity meningioma between January 2019 and December 2020. Risk factors for PTE and ITN were investigated using logistic regression analysis. Analysis of variance was used to determine whether changes in tumor volume were statistically significant. After GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. When postoperative ITN occurred after GKRS, the incidence of postoperative PTE was 18.970-fold (p = 0.009) greater. When a 70% dose volume ≥ 1 cc was used, the possibility of ITN was 5.892-fold (p

Abstract Background Recently, stereotacitc radiosurgery (SRS) has been in the spotlight as an alternative therapeutic option for jugular foramen schwannomas (JFS). While most reported studies focus on the long-term efficacy and safety issues of SRS, none describe the early-onset adverse events (eAEs). We aimed to investigate the incidence, clinical characteristics, and mid-term outcomes of eAEs occurring within six months after SRS for JFS. Methods In this retrospective review, patients who underwent at least six months of follow-up were included among all patients with JFS who have performed SRS at our institution between July 2008 and November 2019. And eAEs were defined as a newly developed neurological deficit or aggravation of pre-existing symptoms during the first six months after SRS. Results Forty-six patients were included in the analysis. The median follow-up period was 50 months (range 9–136). The overall tumor control rate was 91.3%, and the actuarial 3-, 5-, and 10-year progression-free survival rates were 97.8%, 93.8%, and 76.9%, respectively. Of the 46 patients, 16 had eAEs, and the median time to onset of eAEs was one month (range 1–6 months), and the predominant symptoms were lower cranial nerve dysfunctions. Thirteen of 16 patients showed improved eAE symptoms during the follow-up period, and the median resolution time was six months (range 1–52). In 11 (68.8%) of 16 patients with eAEs, transient expansions were observed with a mean of 3.6 months after the onset of eAEs, and the mean difference between the initial tumor volume and the transient expansion volume was more prominent in the patients with eAEs (3.2 cm3 vs. 1.0 cm3; p = 0.057). In univariate analysis, dumbbell-shaped tumors (OR 10.56; p = 0.004) and initial tumor volume (OR 1.32; p = 0.033) were significantly associated with the occurrence of eAEs. Conclusions Although acute adverse events after SRS for JFS are not rare, these acute effects were not permanent and mostly improved with the steroid treatment. Dumbell-shaped and large-volume tumors are significant predictive factors for the occurrence of eAEs. And the transient expansion also seems to be closely related to eAEs. Therefore, clinicians need to be more cautious when treating these patients and closely monitor the occurrence of eAEs.

Abstract Background The brainstem has the critical role of regulating cardiac and respiratory function and it also provides motor and sensory function to the face via the cranial nerves. Despite the observation of a brainstem lesion in a radiological examination, it is difficult to obtain tissues for a pathological diagnosis because of the location and small volume of the brainstem. Thus, we aimed to share our 6‐year experience with stereotactic biopsies from brainstem lesions and confirm the value and safety of stereotactic biopsy on this highly eloquent area in this study. Methods We retrospectively reviewed the medical records of 42 adult patients who underwent stereotactic biopsy on brainstem lesions from 2015 to 2020. The radiological findings, surgical records, pathological diagnosis, and postoperative complications of all patients were analyzed. Results Histopathological diagnoses were made in 40 (95.2%) patients. Astrocytic tumors were diagnosed in 29 (69.0%) patients, diffuse large B cell lymphoma in 5 (11.9%) patients, demyelinating disease in 4 (9.5%) patients, germinoma in 1 (2.4%) patient, and radiation necrosis in 1 (2.4%) patient. In the 40 patients with successful stereotactic biopsy, 10 (25.0%) patients had inconsistent preoperative radiological diagnosis and postoperative pathological diagnosis. In addition, there was a difference between the treatments prescribed by the radiological and pathological diagnoses in 8 out of 10 patients whose diagnoses changed after biopsy. There was no operative mortality among the 42 patients. Conclusions A pathological diagnosis can be made safely and efficiently in brainstem lesions using stereotactic biopsy. This pathological diagnosis will enable patients to receive appropriate treatment.

Abstract Background Focused ultrasound (FUS)-mediated blood–brain barrier (BBB) opening has shown efficacy in removal of amyloid plaque and improvement of cognitive functions in preclinical studies, but this is rarely reported in clinical studies. This study was conducted to evaluate the safety, feasibility and potential benefits of repeated extensive BBB opening. Methods In this open-label, prospective study, six patients with Alzheimer’s disease (AD) were enrolled at Severance Hospital in Korea between August 2020 and September 2020. Five of them completed the study. FUS-mediated BBB opening, targeting the bilateral frontal lobe regions over 20 cm3, was performed twice at three-month intervals. Magnetic resonance imaging, 18F-Florbetaben (FBB) positron emission tomography, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) and comprehensive neuropsychological tests were performed before and after the procedures. Results FUS targeted a mean volume of 21.1 ± 2.7 cm3 and BBB opening was confirmed at 95.7% ± 9.4% of the targeted volume. The frontal-to-other cortical region FBB standardized uptake value ratio at 3 months after the procedure showed a slight decrease, which was statistically significant, compared to the pre-procedure value (− 1.6%, 0.986 vs1.002, P = 0.043). The CGA-NPI score at 2 weeks after the second procedure significantly decreased compared to baseline (2.2 ± 3.0 vs 8.6 ± 6.0, P = 0.042), but recovered after 3 months (5.2 ± 5.8 vs 8.6 ± 6.0, P = 0.89). No adverse effects were observed. Conclusions The repeated and extensive BBB opening in the frontal lobe is safe and feasible for patients with AD. In addition, the BBB opening is potentially beneficial for amyloid removal in AD patients.

Abstract The management of vestibular schwannoma (VS) with residual tumor following incomplete resection remains controversial and little is known regarding postoperative tumor volume changes. The behavior of residual tumors was analyzed for 111 patients who underwent surgery for newly diagnosed VS between September 2006 and July 2017. The postoperative tumor volume changes were assessed during a mean follow-up of 69 months (range 36–147 months). Fifty-three patients underwent imaging surveillance following incomplete resection. There was no residual tumor growth in 44 patients (83%). A significant regression of residual tumor volume was noted in the no growth group at postoperative 1 year (p = 0.028), 2 years (p = 0.012), but not from 3 years onwards. Significant predictors of regrowth were immediate postoperative tumor volume ≥ 0.7 cm3 (HR 10.5, p = 0.020) and residual tumor location other than the internal auditory canal (IAC) (HR 6.2, p = 0.026). The mean time to regrowth was 33 months (range 5–127 months). The 2-, 5-, and 10-year regrowth-free survival rates were 90.6%, 86.8%, and 83%, respectively. In conclusion, significant residual tumor regression could occur within 2 years for a VS with an immediate postoperative tumor volume less than 0.7 cm3 or residual tumor in IAC.

BackgroundDeep brain stimulation is an established treatment for movement disorders such as Parkinson’s disease, essential tremor, and dystonia. However, various complications that occur after deep brain stimulation are a major concern for patients and neurosurgeons.ObjectiveThis study aimed to analyze various complications that occur after deep brain stimulation.MethodsWe reviewed the medical records of patients with a movement disorder who underwent bilateral deep brain stimulation between 2000 and 2020. Among them, patients requiring revision surgery were analyzed.ResultsA total of 426 patients underwent bilateral deep brain stimulation for a movement disorder. The primary disease was Parkinson’s disease in 315 patients, followed by dystonia in 71 patients and essential tremor in 40 patients. Twenty-six (6.1%) patients had complications requiring revision surgery; the most common complication was infection (12 patients, 2.8%).ConclusionVarious complications may occur after deep brain stimulation, and patient prognosis should be improved by reducing complications.

Abstract Background The persistence of adult hippocampal neurogenesis (AHN) is sharply decreased in Alzheimer’s disease (AD). The neuropathologies of AD include the presence of amyloid-β deposition in plaques, tau hyperphosphorylation in neurofibrillary tangles, and cholinergic system degeneration. The focused ultrasound (FUS)-mediated blood-brain barrier opening modulates tau hyperphosphorylation, the accumulation of amyloid-β proteins, and increases in AHN. However, it remains unclear whether FUS can modulate AHN in cholinergic-deficient conditions. In this study, we investigated the effect of FUS on AHN in a cholinergic degeneration rat model of dementia. Methods Adult male Sprague-Dawley rats (n = 48; 200–250 g) were divided into control (phosphate-buffered saline injection), 192 IgG-saporin (SAP), and SAP+FUS groups; in the two latter groups, SAP was injected bilaterally into the lateral ventricle. We applied FUS to the bilateral hippocampus with microbubbles. Immunohistochemistry, enzyme-linked immunosorbent assay, immunoblotting, 5-bromo-2′-deoxyuridine labeling, an acetylcholinesterase assay, and the Morris water maze test were performed to assess choline acetyltransferase, acetylcholinesterase activity, brain-derived neurotrophic factor expression, neural proliferation, and spatial memory, respectively. Statistical significance of differences in between groups was calculated using one-way and two-way analyses of variance followed by Tukey’s multiple comparison test to determine the individual and interactive effects of FUS on immunochemistry and behavioral analysis. P

While focused ultrasound (FUS) is non-invasive, the ultrasound energy is attenuated by the skull which results in differences in energy efficiency among patients. In this study, we investigated the effect of skull variables on the energy efficiency of FUS. The thickness and density of the skull and proportion of the trabecular bone were selected as factors that could affect ultrasound energy transmittance. Sixteen 3D-printed skull models were designed and fabricated to reflect the three factors. The energy of each phantom was measured using an ultrasonic sound field energy measurement system. The thickness and proportion of trabecular bone affected the attenuation of transmitted energy. There was no difference in the density of the trabecular bone. In clinical data, the trabecular bone ratio showed a significantly greater correlation with dose/delivered energy than that of thickness and the skull density ratio. Currently, for clinical non-thermal FUS, the data are not sufficient, but we believe that the results of this study will be helpful in selecting patients and appropriate parameters for FUS treatment.

Deep brain stimulation (DBS) targeting the ventralis intermedius (VIM) nucleus of the thalamus and the posterior subthalamic area (PSA) has been shown to be an effective treatment for essential tremor (ET). The aim of this study was to compare the stimulation-induced side effects of DBS targeting the VIM and PSA using a single electrode. Patients with medication-refractory ET who underwent DBS electrode implantation between July 2011 and October 2020 using a surgical technique that simultaneously targets the VIM and PSA with a single electrode were enrolled in this study. A total of 93 patients with ET who had 115 implanted DBS electrodes (71 unilateral and 22 bilateral) were enrolled. The Clinical Rating Scale for Tremor (CRST) subscores improved from 20.0 preoperatively to 4.3 (78.5% reduction) at 6 months, 6.3 (68.5% reduction) at 1 year, and 6.5 (67.5% reduction) at 2 years postoperation. The best clinical effect was achieved in the PSA at significantly lower stimulation amplitudes. Gait disturbance and clumsiness in the leg was found in 13 patients (14.0%) upon stimulation of the PSA and in significantly few patients upon stimulation of the VIM (p = 0.0002). Fourteen patients (15.1%) experienced dysarthria when the VIM was stimulated; this number was significantly more than that with PSA stimulation (p = 0.0233). Transient paresthesia occurred in 13 patients (14.0%) after PSA stimulation and in six patients (6.5%) after VIM stimulation. Gait disturbance and dysarthria were significantly more prevalent in patients undergoing bilateral DBS than in those undergoing unilateral DBS (p = 0.00112 and p = 0.0011, respectively). Paresthesia resolved either after reducing the amplitude or switching to bipolar stimulation. However, to control gait disturbance and dysarthria, some loss of optimal tremor control was necessary at that particular electrode contact. In the present study, the most common stimulation-induced side effect associated with VIM DBS was dysarthria, while that associated with PSA DBS was gait disturbance. Significantly, more side effects were associated with bilateral DBS than with unilateral DBS. Therefore, changing active DBS contacts to simultaneous targeting of the VIM and PSA may be especially helpful for ameliorating stimulation-induced side effects.

Deep brain stimulation (DBS) in internal globus pallidus is considered to be a good option for controlling generalized dystonia in patients with this condition. In this relation, it is known that DBS has already been shown to have significant effects on primary dystonia, but is seen as controversial in secondary dystonia including cerebral palsy (CP). On the other hand, intrathecal baclofen (ITB) has been known to reduce spasticity and dystonia in patients who did not respond to oral medications or botulinum toxin treatment. Here, we report a patient with dystonic CP, who received the ITB pump implantation long after the DBS and who noted remarkable improvement in the 36-Item Short Form Health Survey, Dystonia Rating Scale, Modified Barthel Index, and visual analog scale scores for pain after an ITB pump implantation was used as compared with DBS. To our knowledge, the present case report is the first to demonstrate the effects of an ITB pump on reducing pain and dystonia and improving quality of life and satisfaction, compared with DBS in a patient with CP.

ObjectiveMagnetic resonance-guided focused ultrasound surgery (MRgFUS) lesioning is a new treatment for brain disorders. However, the skull is a major barrier of ultrasound sonication in MRgFUS because it has an irregular surface and varies its size and shape among individuals. We recently developed the concept of skull density ratio (SDR) to select candidates for MRgFUS from among patients with essential tremor (ET). However, SDR is not the only factor contributing to successful MRgFUS lesioning treatment—refining the target through exact measurement of the ultrasonic echo in the transducer also improves treatment efficacy. In the present study, we carried out MRgFUS lesioning using an autofocusing echo imaging technique. We aimed to evaluate the safety and efficacy of this new approach, especially in patients with low SDR in whom previous focusing methods have failed.MethodsFrom December 2019 to March 2020, we recruited 10 patients with ET or Parkinson’s disease (PD) who had a low SDR. Two patients dropped out of the trial due to the screening failure of other medical diseases. In total, eight patients were included: six with ET who underwent MRgFUS thalamotomy and two with PD who underwent MRgFUS pallidotomy. The autofocusing echo imaging technique was used in all cases.ResultsThe mean SDR of the patients with ET was 0.34 (range: 0.29–0.39), while that of the patients with PD was 0.41 (range: 0.38–0.44). The mean skull volume of patients with ET was 280.57 cm3 (range: 227–319 cm3), while that of the patients with PD was 287.13 cm3 (range: 271–303 cm3). During MRgFUS, a mean of 15 sonications were performed, among which a mean of 5.63 used the autofocusing technique. The mean maximal temperature (Tmax) achieved was 55.88°C (range: 52–59°C), while the mean energy delivered was 34.75 kJ (range: 20–42 kJ) among all patients. No serious adverse events occurred during or after treatment. Tmax or sonication factors (skull volume, SDR, sonication number, autofocusing score, similarity score, energy range, and power) were not correlated with autofocusing technique (p > 0.05, autofocusing score showed a p-value of 0.071).ConclusionUsing autofocusing echo imaging lesioning, a safe and efficient MRgFUS treatment, is available even for patients with a low SDR. Therefore, the indications for MRgFUS lesioning could be expanded to include patients with ET who have an SDR < 0.4 and those with PD who have an SDR < 0.45.Clinical Trial Registrationclinicaltrials.gov, identifier: NCT03935581.

Introduction: To overcome the blood–brain barrier (BBB) which interferes with the effect of chemotherapeutic agents, we performed multiple disruptions of BBB (BBBD) with magnetic resonance-guided focused ultrasound on patients with glioblastoma (GBM) during standard adjuvant temozolomide (TMZ) chemotherapy [clinical trial registration no.NCT03712293 (clinicaltrials.gov)]. We report a 1-year follow-up result of BBBD with TMZ for GBM.Methods: From September 2018 to January 2019, six patients were enrolled (four men and two women, median age: 53 years, range: 50–67 years). Of the six patients, five underwent a total of six cycles of BBBD during standard TMZ adjuvant therapy. One patient underwent three cycles of BBBD but continued with TMZ chemotherapy. The 1-year follow-up results of these six patients were reviewed.Results: The mean follow-up duration was 15.17 ± 1.72 months. Two patients showed a recurrence of tumor at 11 and 16 months, respectively. One underwent surgery, and the other patient was restarted with TMZ chemotherapy due to the tumor location with a highly possibility of surgical complications. The survival rate up to 1 year was 100%, and the other four patients are on observation without recurrence. None of the six patients had immediate or delayed BBBD-related complications.Conclusion: Multiple BBBDs can be regarded as a safe procedure without long-term complications, and it seems to have some survival benefits. However, since TMZ partially crosses the BBB, a further extended study with large numbers would be needed to evaluate the benefits of BBBD resulting in an increase of TMZ concentration. This study opened a new therapeutic strategy for GBM by combining BBBD with a larger molecular agent.

Although there have been reports of promising results regarding the transplantation of mesenchymal stem cells (MSCs) for neurodegenerative diseases through the use of neuronal differentiation or control of the microenvironment, traditional surgical transplantation methods like parenchymal or intravenous injection have limitations such as secondary injuries in the brain, infection, and low survival rate of stem cells in the target site. Focused ultrasound (FUS) treatment is an emerging modality for the treatment of brain diseases, including neurodegenerative disorders. The various biological effects of FUS treatment have been investigated; therefore, the goal is now to improve the delivery efficiency and function of MSCs by capitalizing on the advantages of FUS. In this study, we demonstrated that FUS increases MSC transplantation into brain tissue by >2-fold, and that this finding might be related to the activation of intercellular adhesion molecule-1 in endothelial and subendothelial cells and vascular adhesion molecule-1 in endothelial cells. Keywords: Stem cell transplantation, Mesenchymal stem cells, Cell adhesion molecules, Cell migration, Cytokines, Stem cell-microenvironment interactions

Background: Intrathecal baclofen (ITB) therapy, a viable alternative for unsuitable candidates of conventional spasticity medications, is a preferred method of administration over the oral route. Owing to its enhanced bioavailability, ITB ensures a more effective delivery at the target site. Objective: There is a lack of conclusive evidence regarding the use of ITB treatment in managing ambulatory patients with spastic dystonia. Before ITB pump implantation, patients commonly undergo an ITB bolus injection trial to rule out potential adverse reactions and verify the therapeutic effects on hypertonic issues. In this report, we highlight a case of spastic dystonia, particularly focusing on an ambulatory patient who demonstrated significant improvement in both the modified Ashworth scale (MAS) score and gait pattern following the ITB injection trial. Case report: This case report outlines the medical history of a 67-year-old male diagnosed with left-side hemiplegia and spastic dystonia, resulting from his second episode of intracranial hemorrhage in the right thalamus. An ITB injection trial was initiated because the patient was not suitable for continued botulinum toxin injections and oral medications. This was due to the persistent occurrence of spastic dystonia in both the upper and lower extremities. The patient underwent a four-day ITB injection trial with progressively increasing doses, resulting in improved MAS scores and gait parameters, including cadence, step length, step time, stride length, and stride time were increased. Particularly, kinematic gait analysis demonstrates a substantial improvement of increased knee flexion in the swing phase in stiff knee gait pattern. These findings indicated a gradual reduction in spasticity-related symptoms, signifying the positive effect of the ITB injection trial. The patient eventually received an ITB pump implantation. Conclusion: In this post-stroke patient with spastic dystonia, ITB therapy has demonstrated effective and substantial management of spasticity, along with improvement in gait patterns. [ABSTRACT FROM AUTHOR]

In this paper, we report on the ablation of Ti thin films with a thickness of 100 nm, while minimizing defects. Ti thin films are used in the TFT of µ-LEDs, and repair processing is required to increase the production yield of µ-LEDs. The repair process involves selectively ablating specific regions with a femtosecond laser, which must be done with precision to ensure proper TFT operation. Precise ablation means that defects, such as burrs, ripples, and substrate ablation, do not occur. To implement minimizing defects, we conducted COMSOL Multiphysics simulations using both Gaussian and flat-top beams. We irradiated the sample with a laser under various conditions, including pulse fluence, number of pulses, and beam deformation, and assessed the resulting ablation quality. Through careful selection of the laser conditions, which include flat-top beam with 0.28 J/cm2 fluence and 7 pulses, we were able to minimize burrs, ripples, and substrate ablation, resulting in neat and minimizing defect of 100 nm Ti ablation. [ABSTRACT FROM AUTHOR]

Post-hypoxic myoclonus (PHM) and Lance–Adams syndrome (LAS) are rare conditions following cardiopulmonary resuscitation. The aim of this study was to identify functional activity in the cerebral cortex after a hypoxic event and to investigate alterations that could be modulated by deep brain stimulation (DBS). A voxel-based subtraction analysis of serial positron emission tomography (PET) scans was performed in a 34-year-old woman with chronic medically refractory PHM that improved with bilateral globus pallidus internus (Gpi) DBS implanted three years after the hypoxic event. The patient required low-frequency stimulation to show myoclonus improvement. Using voxel-based statistical parametric mapping, we identified a decrease in glucose metabolism in the prefrontal lobe including the dorsolateral, orbito-, and inferior prefrontal cortex, which was suspected to be the origin of the myoclonus from postoperative PET/magnetic resonance imaging (MRI) after DBS. Based on the present study results, voxel-based subtraction of PET appears to be a useful approach for monitoring patients with PHM treated with DBS. Further investigation and continuous follow-up on the use of PET analysis and DBS treatment for patients with PHM are necessary to help understanding the pathophysiology of PHM, or LAS.

Thalamotomy at the ventralis intermedius nucleus for essential tremor is known to cause changes in motor circuitry, but how a focal lesion leads to progressive changes in connectivity is not clear. To understand the mechanisms by which thalamotomy exerts enduring effects on motor circuitry, a quantitative analysis of directed or effective connectivity among motor-related areas is required. We characterized changes in effective connectivity of the motor system following thalamotomy using (spectral) dynamic causal modeling (spDCM) for resting-state fMRI. To differentiate long-lasting treatment effects from transient effects, and to identify symptom-related changes in effective connectivity, we subject longitudinal resting-state fMRI data to spDCM, acquired 1 day prior to, and 1 day, 7 days, and 3 months after thalamotomy using a non-cranium-opening MRI-guided focused ultrasound ablation technique. For the group-level (between subject) analysis of longitudinal (between-session) effects, we introduce a multilevel parametric empirical Bayes (PEB) analysis for spDCM. We found remarkably selective and consistent changes in effective connectivity from the ventrolateral nuclei and the supplementary motor area to the contralateral dentate nucleus after thalamotomy, which may be mediated via a polysynaptic thalamic–cortical–cerebellar motor loop. Crucially, changes in effective connectivity predicted changes in clinical motor-symptom scores after thalamotomy. This study speaks to the efficacy of thalamotomy in regulating the dentate nucleus in the context of treating essential tremor. Furthermore, it illustrates the utility of PEB for group-level analysis of dynamic causal modeling in quantifying longitudinal changes in effective connectivity; i.e., measuring long-term plasticity in human subjects non-invasively.

The combinatorial approach of anthropogenic activities and CO2 sequestration is becoming a global research trend to alleviate the average global temperature. Although microalgae have been widely used to capture CO2 from industrial flue gas, the application of bioproducts was limited to bioenergy due to the controversy over the quality and safety of the products in the food and feed industry. Herein, the waste CO2 emitted from large point sources was directly captured using astaxanthin-hyperproducing microalgae Haematococcus pluvialis. Astaxanthin production was successfully carried out using the hypochlorous acid water-based axenic culture process under highly contamination-prone outdoor conditions. Consequently, after 36 days of autotrophic induction, the productivity of biomass and astaxanthin of H. pluvialis (the mutant) reached 0.127 g L−1 day−1 and 5.47 mg L−1 day−1 under high summer temperatures, respectively, which was 38% and 48% higher than that of wild type cell. After grinding the wet astaxanthin-enriched biomass, the extract was successfully approved by compliance validation testing from Korea Food and Drug Administration. The assorted feed improved an immune system of the poultry without causing any side effects. The flue gas-based bioproducts could certainly be used for health functional food for animals in the future.

Purpose: Glioblastoma (GBM) is an intractable disease for which various treatments have been attempted, but with little effect. This study aimed to measure the effect of photodynamic therapy (PDT) and sonodynamic therapy (SDT), which are currently being used to treat brain tumors, as well as sono-photodynamic therapy (SPDT), which is the combination of these two. Materials and Methods: Four groups of Sprague-Dawley rats were injected with C6 glioma cells in a cortical region and treated with PDT, SDT, and SPDT. Gd-MRI was monitored weekly and 18F-FDG-PET the day before and 1 week after the treatment. The acoustic power used during sonication was 5.5 W/cm2 using a 0.5-MHz single-element transducer. The 633-nm laser was illuminated at 100 J/cm2 . Oxidative stress and apoptosis markers were evaluated 3 days after treatment using immunohistochemistry (IHC): 4-HNE, 8-OhdG, and Caspase-3. Results: A decrease in tumor volume was observed in MRI imaging 12 days after the treatment in the PDT group (p<0.05), but the SDT group showed a slight increase compared to the 5-Ala group. The high expression rates of reactive oxygen species-related factors, such as 8-OhdG (p<0.001) and Caspase-3 (p<0.001), were observed in the SPDT group compared to other groups in IHC. Conclusion: Our findings show that light with sensitizers can inhibit GBM growth, but not ultrasound. Although SPDT did not show the combined effect in MRI, high oxidative stress was observed in IHC. Further studies are needed to investigate the safety parameters to apply ultrasound in GBM. [ABSTRACT FROM AUTHOR]

Objective: The blood-brain barrier (BBB) is an obstacle for molecules to pass through from blood to the brain. Focused ultrasound is a new method which temporarily opens the BBB, which makes pharmaceutical delivery or removal of neurodegenerative proteins possible. This study was demonstrated to review our BBB opening procedure with magnetic resonance guided images and find specific patterns in the BBB opening. Methods: In this study, we reviewed the procedures and results of two clinical studies on BBB opening using focused ultrasound regarding its safety and clinical efficacy. Magnetic resonance images were also reviewed to discover any specific findings. Results: Two clinical trials showed clinical benefits. All clinical trials demonstrated safe BBB opening, with no specific side effects. Magnetic resonance imaging showed temporary T1 contrast enhancement in the sonication area, verifying the BBB opening. Several low-signal intensity spots were observed in the T2 susceptibility-weighted angiography images, which were also reversible and temporary. Although these spots can be considered as microbleeding, evidence suggests these are not ordinary microbleeding but an indicator for adequate BBB opening. Conclusion: Magnetic resonance images proved safe and efficient BBB opening in humans, using focused ultrasound. [ABSTRACT FROM AUTHOR]