Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

Progress in magnetic resonance imaging of the glymphatic system

The glymphatic system(GS)is a newly discovered brain anatomy.Its discovery improves our understanding of brain fluid flow and waste removal paths and provides an anatomical basis for the flow of cerebral interstitial fluid(ISF)and cerebrospinal fluid(CSF).GS occurs through a normal exchange within perivascular space(PVS),facilitating the elimination of metabolic wastes generated by nerve cells from the brain.Therefore,the GS is mainly responsible for the removal of metabolic waste.Reduced GS activity has been observed to be associated with central nervous system disorders such as cerebral small vessel disease(CSVD)and neurodegenerative diseases.Its activity is expected to be an indicator for diagnosing diseases and predicting their prognosis.This review introduces the magnetic resonance imaging(MRI)technology related to the GS suitable for clinical use and the difference in the system's activity in normal and abnormal states.Through a summary of previous research,imaging methods suitable for monitoring the activity of the GS in the clinic were proposed,and their diagnostic effect on different brain disorders was analyzed.This review aims to clarify ideas for the clinical translation of basic research focusing on GS and provide future clinical research directions and perspectives.

Trigeminal Ganglioneuroma in the Middle-posterior Cranial Fossa： a Case Report

GANGLIONEUROMA is considered as the most mature and noninvasive form of neuroblastic tumors. It derives from neural crest cells, and can arise from wherever sympathetic tissue exists, including neck, posterior mediastinum, adrenal gland, retroperitoneum and pelvis. The two most common locations for this tumor are retroperitoneum and posterior mediastinum; infrequently it occurs in the intracranial re-gion,2-8 with only three cases has been reported arising from trigeminal nerve.2-4 The current paper presents a 49-year-old male patient with a ganglioneuroma arising from right trigeminal ganglion and extending to the mid-dle-posterior cranial fossa. We summarized the clinical and diagnostic characteristics of this extremely rare tumor, in comparison with the three reported cases in literatures.

Xenopus Tbx6 mediates posterior patterning via activation of Wnt and FGF signalling

In vertebrates, the patterning of anterior-posterior （AP） axis is a fundamental process during embryogenesis. Wnt and FGF signalling pathways play important roles in regulating the patterning of embryo AP axis. Mouse Tbx6 encodes a transcription factor that has been demonstrated to be involved in the specification of the posterior tissue in mouse embryonic body. Here, we prove that morpholino-induced knockdown of XTbx6 impairs posterior development, indicating the requirement of XTbx6 in this process. Meanwhile, gain of XTbx6 function is sufficient to induce ectopic posterior structures in Xenopus embryos. Furthermore, XTbx6 activates the expression of Xwnt8 and FGF8, which are two mediators of posterior development, suggesting a mechanism by which XTbx6 modulates posterior patterning via Wnt and FGF signalling pathway activation.

A composite micromotor driven by self-thermophoresis and Brownian rectification

Brownian motors and self-phoretic microswimmers are two typical micromotors,for which thermal fluctuations play different roles.Brownian motors utilize thermal noise to acquire unidirectional motion,while thermal fluctuations randomize the self-propulsion of self-phoretic microswimmers.Here we perform mesoscale simulations to study a composite micromotor composed of a self-thermophoretic Janus particle under a time-modulated external ratchet potential.The composite motor exhibits a unidirectional transport,whose direction can be reversed by tuning the modulation frequency of the external potential.The maximum transport capability is close to the superposition of the drift speed of the pure Brownian motor and the self-propelling speed of the pure self-thermophoretic particle.Moreover,the hydrodynamic effect influences the orientation of the Janus particle in the ratched potential,hence also the performance of the composite motor.Our work thus provides an enlightening attempt to actively exploit inevitable thermal fluctuations in the implementation of the self-phoretic microswimmers.

Diffusion of a chemically active colloidal particle in composite channels

Diffusion of colloidal particles in microchannels has been extensively investigated,where the channel wall is either a no-slip or a slip-passive boundary.However,in the context of active fluids,driving boundary walls are ubiquitous and are expected to have a substantial effect on the particle dynamics.By mesoscale simulations,we study the diffusion of a chemically active colloidal particle in composite channels,which are constructed by alternately arranging the no-slip and diffusio-osmotic boundary walls.In this case,the chemical reaction catalyzed by the active colloidal particle creates a local chemical gradient along the channel wall,which drives a diffusio-osmotic flow parallel to the wall.We show that the diffusio-osmotic flow can significantly change the spatial distribution and diffusion dynamics of the colloidal particle in the composite channels.By modulating the surface properties of the channel wall,we can achieve different patterns of colloidal position distribution.The findings thus propose a novel possibility to manipulate colloidal diffusion in microfluidics,and highlight the importance of driving boundary walls in dynamics of colloidal particles in microchannels.

Recent research hotspots in sequencing and the pancreatic neuroendocrine tumor microenvironment

Multiple endocrine neoplasia 1(MEN1)syndrome,a disease arising from a genetic predisposition to tumor development caused by MEN1 loss-of-function mutations,is characterized by the combined occurrence of neuroendocrine tumors in multiple human organs.With advances in diagnostic technologies and improvements in living standards.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits

Actinidia arguta,the most widely distributed Actinidia species and the second cultivated species in the genus,can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit,rapid softening,and excellent cold tolerance.Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear.Here,we generated a chromosome-scale genome assembly of an autotetraploid male A.arguta accession.The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes.Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups,Southern and Northern,which first diverged 12.9 million years ago.A.arguta underwent two prominent expansions and one demographic bottleneck from the midPleistocene climate transition to the late Pleistocene.Population genomics studies using paleoclimate data enabled us to discern the evolution of the species’adaptation to different historical environments.Three genes(AaCEL1,AaPME1,and AaDOF1)related to flesh softening were identified by multi-omics analysis,and their ability to accelerate flesh softening was verified through transient expression assays.A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome(Chr3)or autosomal chromosomes showed biased expression during stamen or carpel development.This chromosome-level assembly of the autotetraploid A.arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A.arguta.

Residual inflammatory risk predicts long-term outcomes following stenting for symptomatic intracranial atherosclerotic stenosis

Background and purpose Residual inflammatory risk(RIR)can predict the unfavourable outcomes in patients with minor ischaemic stroke.However,the impact of preprocedural RIR on long-term outcomes in patients with symptomatic intracranial atherosclerotic stenosis(sICAS)who underwent stenting remains understudied.Methods This retrospective,single-centre cohort study evaluated consecutive patients with severe sICAS who underwent intracranial stenting.Patients were categorised into four groups based on preprocedural high-sensitivity C-reactive protein(hs-CRP)and low-density lipoprotein cholesterol(LDL-C):residual cholesterol inflammatory risk(RCIR,hs-CRP≥3 mg/L and LDL-C≥2.6 mmol/L),RIR(hs-CRP≥3 mg/L and LDL-C<2.6 mmol/L),residual cholesterol risk(RCR,hs-CRP<3 mg/L and LDL-C≥2.6 mmol/L)and no residual risk(NRR,hs-CRP<3 mg/L and LDL-C<2.6 mmol/L).The long-term clinical outcomes included recurrent ischaemic stroke and death.The long-term imaging outcomes consisted of in-stent restenosis(ISR)and symptomatic ISR(sISR)after stenting.Results In this study,952 patients were included,with 751(78.9%)being male.Forty-six cases were categorised into the RCIR group,211 into the RIR group,107 into the RCR group and 588 into the NRR group.Patients with RCIR(adjusted HR 6.163;95%CI 2.603 to 14.589;p<0.001)and RIR(adjusted HR 2.205;95%CI 1.294 to 3.757;p=0.004)had higher risks of recurrent ischaemic stroke than those with NRR during the 54 months of median follow-up time.Patients with RCIR(adjusted HR 3.604;95%CI 1.431 to 9.072;p=0.007)were more likely to occur ISR,and patients in the RIR group showed a significant increase in the risk of sISR(adjusted HR 2.402;95%CI 1.078 to 5.351;p=0.032)compared with those in the NRR group with a median follow-up time of 11.9 months.Conclusions In patients with sICAS,preprocedural RIR may predict long-term recurrent ischaemic stroke,ISR and sISR following intracranial stenting.

Perfusion and plaque evaluation to predict recurrent stroke in symptomatic middle cerebral artery stenosis

Background and purpose We investigated the baseline demographics of patients with severe unilateral atherosclerotic stenosis of the middle cerebral artery(MCA)using multimodal MRI and evaluated the haemodynamic impairments and plaque characteristics of patients who had a recurrent stroke.Materials and methods We retrospectively recruited consecutive patients with severe unilateral atherosclerotic MCA stenosis who underwent arterial spin labelling(ASL)with postlabelling delay(PLD)of 1.5 and 2.5 s,and vessel wall MRI.For each PLD,cerebral blood flow(CBF)maps were generated.Hypoperfusion volume ratio(HVR)from 2 PLD CBF was calculated.An HVR value≥50%was considered as severe HVR.Plaque areas,plaque burden,plaque length and remodelling index were measured.Plaque enhancement at maximal lumen narrowing site were graded.Baseline clinical and imaging characteristics were compared between patients with(event+)and without(event?)1 year ischaemic events.Results Forty-three patients(47.23±12.15 years;28 men)were enrolled in this study.Seven patients had an HVR≥50%.During the 1-year follow-up,7 patients had experienced a recurrent stroke.HVR were significantly higher in the event+than event?(53.17%±29.82%vs 16.9%±15.57%,p=0.0002),whereas no significant difference was detected in plaque areas,plaque burden,remodelling index,plaque length and plaque enhancement grade.The multivariable analysis revealed that a severe HVR was significantly associated with a recurrent stroke(Odds ratio=12.93,95%confidence interval 1.57 to 106.24,p=0.017)after adjusted by hypertension and smoking.Conclusion HVR obtained from two PLD ASL may be a useful imaging predictor of recurrent stroke.

Intra-individual comparison of different gadolinium-based contrast agents in the quantitative evaluation of C6 glioma with dynamic contrast-enhanced magnetic resonance imaging

This experiment aimed to compare the ionic （Gadodiamide, Gd-DTPA-BMA） and non-ionic （Gadopentetate dimeglumine, Gd-DTPA） gadolinium-based contrast agents （GBCA） in the quantitative evaluation of C6 glioma with dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. A C6 glioma model was established in 12 Wistar rats, and magnetic resonance （MR） scans were performed six days after tumor implantation. Imaging was performed using a 3.0-T MR scanner with a 7-inch handmade circular coil. Pre-contrast T1 mapping and dynamic contrast-enhanced T1WI after a bolus injection （0.2 mL s 1） of GBCA at 0.4 mmol kg-1 were performed. Each rat received two DCE-MRI scans, 24 h apart. The first and second scans were performed using Gd-DTPA-BMA and Gd-DTPA, respectively. Image data were processed using the Patlak model. Both Kns and Vp maps were generated. Tumors were manually segmented on all 3D K and Vp maps. Pixel counts and mean values were recorded for use in a paired t-test. Three radiologists independently performed the tumor segmentation and value calculation. The agreements from different observers were subjective to the intra-class correlation coefficient （ICC）. Readers demonstrated that the pixel counts of tumors in/Crns maps were higher with Gd-DTPA-BMA than with Gd-DTPA （P〈0.001, all readers）. Although the/（r,,s values were higher with Gd-DTPA-BMA than with Gd-DTPA, there was no statistical significance （P〉0.05, all readers）. The pixel counts of tumors in Vp maps, as well as Vp values, showed no obvious difference between the two agents （P〉0.05, all readers）. Excellent interobserver measurement reproducibility and reliability were demonstrated in the ICC tests. The Gd-DTPA-BMA contrast agent had significantly higher pixel counts of glioma in the maps, and an increased tendency for average/Us values, indicating that DCE-MRI with Gd-DTPA-BMA may be more suitable and sensitive for the evaluation of glioma.

Association of fluid-attenuated inversion recovery vascular hyperintensity with ischaemic events in internal carotid artery or middle cerebral artery occlusion

Background and purpose Individuals with intracranial artery occlusion have high rates of ischaemic events and recurrence.It has been challenging to identify patients who had high-risk stroke using a simple,valid and non-invasive screening approach.This study aimed to investigate whether fluid-attenuated inversion recovery(FLAIR)vascular hyperintensity(FVH),a specific imaging sign on the FLAIR sequence,could be a predictor of ischaemic events in a population with internal carotid artery(ICA)or middle cerebral artery(MCA)occlusion.Methods We retrospectively analysed 147 patients(mean 60.43±12.83 years)with 149 lesions,including 37 asymptomatic and 112 symptomatic cases of ICA or MCA occlusion.Symptomatic occlusion was considered if ischaemic events were present in the relevant territory within 90 days.FVH Alberta Stroke Program Early Computed Tomography Score(FVH-ASPECTS:0-7,with 0 indicating absence of FVH and 7 suggesting prominent FVH)and collateral circulation grade were assessed for each participant.Multivariable logistic regression analysis was performed to detect independent markers associated with symptomatic status.Results A lower FVH-ASPECTS was associated with a more favourable collateral circulation grade(rho=−0.464,p<0.0001).The FVH-ASPECTS was significantly lower in the asymptomatic occlusion group than in the symptomatic occlusion group(p<0.0001).FVH-ASPECTS(Odd ratio,2.973;95%confidence interval,1.849 to 4.781;p<0.0001)was independently associated with symptomatic status after adjustment for age,sex,lesion location and collateral circulation grade in the multivariate logistic regression.The area under the curve was 0.861 for the use of FVH-ASPECTS to identify symptomatic occlusion.Conclusions The ability to discriminate symptomatic from asymptomatic occlusion suggests that FVH may be a predictor of stroke.As a simple imaging sign,FVH may serve as a surrogate for haemodynamic impairments and can be used to identify high-risk stroke cases early in ICA or MCA occlusion.

Current applications for magnetic resonance-guided focused ultrasound in the treatment of Parkinson’s disease

Magnetic resonance-guided focused ultrasound(MRgFUS)is a novel and minimally invasive technology.Since the US Food and Drug Administration approved unilateral ventral intermediate nucleus-MRgFUS for medication-refractory essential tremor in 2016,studies on new indications,such as Parkinson’s disease(PD),psychiatric diseases,and brain tumors,have been on the rise,and MRgFUS has become a promising method to treat such neurological diseases.Currently,as the second most common degenerative disease,PD is a research hotspot in the field of MRgFUS.The actions of MRgFUS on the brain range from thermoablation,blood-brain barrier(BBB)opening,to neuromodulation.Intensity is a key determinant of ultrasound actions.Generally,high intensity can be used to precisely thermoablate brain targets,whereas low intensity can be used as molecular therapies to modulate neuronal activity and open the BBB in conjunction with injected microbubbles.Here,we aimed to summarize advances in the application of MRgFUS for the treatment of PD,with a focus on thermal ablation,BBB opening,and neuromodulation,in the hope of informing clinicians of current applications.

多核磁共振成像助力新冠肺炎疫情防控

新型冠状病毒肺炎(简称“新冠肺炎”)疫情在全球仍持续处于大流行阶段,目前全球范围内累积确诊病例超5亿。肺部和脑部损伤在新冠肺炎患者中最为常见,一些患者在出院后数周乃至数月仍有相关症状。医学影像技术在受累器官的结构和功能的诊断评估中发挥了重要作用。本文回顾了临床放射学在新型冠状病毒感染引起的肺部和脑部损伤评估中的应用现状,介绍了我们用于新冠肺炎预测与功能评估的新影像技术,进一步阐述了多核肺部磁共振成像原理及其在我国的发展,简述了基于我国自主研发的多核肺部磁共振成像装备对新冠肺炎患者肺部功能改变的定量可视化评估,以及对肺部和脑部损伤之间的关联研究。研究结果表明多核磁共振成像在新型冠状病毒致肺功能损伤评估中具有独特优势,可点亮传统影像的肺部“盲区”。

T2 relaxation time measurements in the brains of scalded rats

This study aimed to evaluate the T2 relaxation time of the brain in severely scalded rats using a magnetic resonance （MR） T2 mapping sequence, and to investigate the correlation between T2 relaxation time and plasma glucose level. Twenty-eight Wistar rats were randomly divided into the scalded group （n = 21）and control group （n = 7）. Magnetic resonance scans were performed with T1WI, T2WI, and T2-mapping sequences in the scalded group; the scans were performed 1 day prior to scalding and 1, 3, 5, and 7 days post-scalding; in addition, identical MR scans were performed in the control group at the same time points. T2-maps were generated and T2 relaxation times were acquired from the following brain regions： the hippocampus, thalamus, caudate-putamen, and cerebrum. Pathological changes of the hippocampus were observed. The plasma glucose level of each rat was measured before each MR scan, and a correlation analysis was performed between T2 relaxation time and plasma glucose level. We found that conventional T 1WI and T2WI did not reveal any abnormal signals or morphological changes in the hippocampus, thalamus, caudate-putamen,： or cerebrum post-scalding. Both the T2 relaxation times of the selected brain regions and plasma glucose levels increased 1, 3, and 5 days post-scalding, and returned to normal levels 7 days post-scalding. The most marked increase of T2 relaxation time was found in the hippocampus; similar changes were also revealed in the thalamus, caudate-putamen, and cerebrum. No correlation was found between T2 relaxation time and plasma glucose level in scalded rats. Pathological observation of the hippocampus showed edema 1, 3, and 5 days post-scalding, with recovery to normal findings at 7 days post-scalding. Thus, we concluded that T2 mapping is a sensitive method for detecting and monitoring scald injury in the rat brain. As the hippocampus is the main region for modulating a stress reaction, it showed significantly increased water content along with an increased plasma glucose level post-scalding.

Light-driven single-cell rotational adhesion frequency assay

The interaction between cell surface receptors and extracellular ligands is highly related to many physiological processes in living systems.Many techniques have been developed to measure the ligand-receptor binding kinetics at the single-cell level.However,few techniques can measure the physiologically relevant shear binding affinity over a single cell in the clinical environment.Here,we develop a new optical technique,termed single-cell rotational adhesion frequency assay(scRAFA),that mimics in vivo cell adhesion to achieve label-free determination of both homogeneous and heterogeneous binding kinetics of targeted cells at the subcellular level.Moreover,the scRAFA is also applicable to analyze the binding affinities on a single cell in native human biofluids.With its superior performance and general applicability,scRAFA is expected to find applications in study of the spatial organization of cell surface receptors and diagnosis of infectious diseases.

Predicting tremor improvement after MRgFUS thalamotomy in essential tremor from preoperative spontaneous brain activity:A machine learning approach

Magnetic resonance-guided focused ultrasound surgery(MRgFUS)thalamotomy is an emerging technique for medication-refractory essential tremor(ET),but with variable outcomes.This study used pattern regression analysis to identify brain signatures predictive of tremor improvements.Fifty-four ET patients(mean age=63.06 years,standard deviation(SD)=10.55 years,38 males)underwent unilateral MRg FUS thalamotomy and were scanned for resting-state functional magnetic resonance imaging(rsf MRI).Seventy-four healthy controls(mean age=58.09 years,SD=10.30 years,38 males)were recruited for comparison.Tremor responses at 12 months posttreatment were evaluated by the Clinical Rating Scale for Tremor.The fractional amplitude of low-frequency fluctuations(f ALFF)was calculated from rs-f MRI data.Two-sample t-test was used to generate a disease-specific mask,within which Multivariate Kernel Ridge Regression analyses were conducted.Predicted and actual clinical scores were compared using Pearson's correlation coefficient(r)and normalized mean squared error(Norm.MSE).Permutation test and leave-one-out strategy were applied for results validation.KRR identified f ALFF patterns that significantly predicted the hand tremor improvement(r=0.23,P=0.025;Norm.MSE=0.05,P=0.026)and the postural tremor improvement(r=0.28,P=0.025;Norm.MSE=0.06,P=0.023),but not action tremor improvement.Lobule VI of right cerebellum(Cerebelum_6_R),right superior occipital gyrus(Occipital_Sup_R)and lobule X of vermis(Vermis_10)contributed most for hand tremor prediction(normalized weights(NW):2.77%,2.40%,2.34%)while Vermis_10,left supplementary motor area(Supp_Motor_Area_L)and right hippocampus(Hippocampus_R)for postural tremor prediction(NW:2.69%,2.12%,2.05%).The low contributing NW of the individual brain regions suggested that the f ALFF pattern as a whole is an overall predicting feature.Preoperative f ALFF pattern predicts tremor benefits induced by MRg FUS thalamotomy.Clinical Trials.gov number:NCT04570046.