spinal cord

脊髓
  • 文章类型: Journal Article
    背景:神经系统发育的关键步骤涉及神经祖细胞规格和定位的协调控制。脊椎动物中枢神经系统的长期模型假设,瞬时解剖区室-称为神经细胞-具有沿着胚胎前后神经轴定位神经祖细胞的功能。这种神经细胞在胚胎后脑中很明显-包含六个形态上明显的菱形-但其他神经细胞缺乏明确的形态边界,而是由不同的标准定义。例如基因表达模式和移植实验结果的差异。因此,菱形(r)6后面的后脑(CHB)已被可变地提议包含2至5个“伪菱形”,但是缺乏全面的分子数据排除了对这种结构的详细定义。
    方法:我们使用单细胞多体组分析,可以同时表征单个细胞核的基因表达和染色质状态,在发育中的斑马鱼CNS中鉴定和表征CHB祖细胞。
    结果:我们将CHB祖细胞鉴定为转录上不同的群体,它还具有可接近的转录因子结合基序的独特概况,相对于r6和脊髓。这种CHB群体可以细分沿其背腹轴的基础上的分子特征,但是我们没有发现任何分子证据表明它含有多个伪菱形。我们进一步观察到CHB在最早的胚胎阶段与r6密切相关,但随着时间的推移变得更加分歧,它是由独特的基因调控网络定义的。
    结论:我们得出结论,早期CHB代表一个单一的神经区室,不能被分子细分为假菱形,它可能与r6共享胚胎起源。
    BACKGROUND: A key step in nervous system development involves the coordinated control of neural progenitor specification and positioning. A long-standing model for the vertebrate CNS postulates that transient anatomical compartments - known as neuromeres - function to position neural progenitors along the embryonic anteroposterior neuraxis. Such neuromeres are apparent in the embryonic hindbrain - that contains six rhombomeres with morphologically apparent boundaries - but other neuromeres lack clear morphological boundaries and have instead been defined by different criteria, such as differences in gene expression patterns and the outcomes of transplantation experiments. Accordingly, the caudal hindbrain (CHB) posterior to rhombomere (r) 6 has been variably proposed to contain from two to five \'pseudo-rhombomeres\', but the lack of comprehensive molecular data has precluded a detailed definition of such structures.
    METHODS: We used single-cell Multiome analysis, which allows simultaneous characterization of gene expression and chromatin state of individual cell nuclei, to identify and characterize CHB progenitors in the developing zebrafish CNS.
    RESULTS: We identified CHB progenitors as a transcriptionally distinct population, that also possesses a unique profile of accessible transcription factor binding motifs, relative to both r6 and the spinal cord. This CHB population can be subdivided along its dorsoventral axis based on molecular characteristics, but we do not find any molecular evidence that it contains multiple pseudo-rhombomeres. We further observe that the CHB is closely related to r6 at the earliest embryonic stages, but becomes more divergent over time, and that it is defined by a unique gene regulatory network.
    CONCLUSIONS: We conclude that the early CHB represents a single neuromere compartment that cannot be molecularly subdivided into pseudo-rhombomeres and that it may share an embryonic origin with r6.
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  • 文章类型: Journal Article
    实验性自身免疫性脑脊髓炎(EAE)是一种影响动物中枢神经系统(CNS)的脱髓鞘疾病,与人类多发性硬化症的几种临床和分子特征相似。单纯疱疹病毒1型(HSV-1)感染主要引起唇疱疹和眼部疾病,然而最终,它也可以到达中枢神经系统,导致急性脑炎.值得注意的是,相当比例的健康个体可能患有无症状HSV-1脑感染伴慢性脑炎症,这是由于神经元的持续性潜伏感染.因为细胞衰老被认为是导致各种神经退行性疾病发展的潜在因素,包括多发性硬化症,病毒感染可能会导致中枢神经系统过早衰老,可能会增加对此类疾病的易感性,在这里,我们检查了无症状HSV-1脑感染小鼠的大脑和脊髓中衰老相关标志物的存在,EAE,这两个条件。在所有场景中,我们发现中枢神经系统中衰老生物标志物的显著增加,根据分析组的不同,存在一些差异.值得注意的是,一些衰老生物标志物仅在具有组合条件的小鼠中观察到。这些结果表明无症状HSV-1脑感染和EAE与CNS中衰老生物标志物的显著表达相关。
    Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.
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  • 文章类型: Journal Article
    目的:紫杉醇(PTX)被广泛用于各种实体瘤的治疗,经常导致紫杉醇诱导的周围神经病变(PIPN)。本研究旨在调查PIPN行为表现和潜在发病机制的性别差异,并寻找临床有效的干预措施。
    方法:雄性和雌性C57BL/6小鼠(5-6周和12个月,体重18-30g),每隔一天以2mg/kg的剂量腹膜内(i.p.)施用在盐水(NaCl0.9%)中稀释的紫杉醇,共注射4次。在给药前后进行VonFrey和热板测试,以确认PIPN模型的成功建立,并评估PIPN的疼痛和PD-L1的镇痛作用。PTX给药后第14天,通过鞘内(i.t.)途径将PD-L1蛋白(10ng/pc)注射到PIPN中。为了击倒脊髓中的TRPV1,腺相关病毒9(AAV9)-Trpv1-RNAi(5μL,通过i.t.途径缓慢注射1×1013vg/mL)。AAV9交付四周后,通过免疫荧光染色和Western印迹验证TRPV1表达的下调.通过蛋白质印迹法测量PD-L1、TRPV1和CGRP的水平,RT-PCR,和免疫荧光染色。RT-PCR检测TNF-α和IL-1β水平。
    结果:对照组雌性小鼠的脊髓中TRPV1和CGRP蛋白和mRNA水平高于对照组雄性小鼠。PTX诱导的雌性PIPN小鼠的伤害性行为大于雄性PIPN小鼠,如TRPV1和CGRP的表达增加所示。雌性小鼠PD-L1对机械性痛觉过敏和热敏感性的镇痛作用明显大于雄性小鼠,计算出的相对治疗水平增加了大约2.717倍和2.303倍,分别。PD-L1和CGRP与TRPV1部分共定位在小鼠脊髓的背角。在AAV9介导的脊髓特异性降低TRPV1表达后,观察到PD-L1在PIPN小鼠中的镇痛作用是通过下调TRPV1和CGRP表达来介导的。
    结论:PTX诱导的PIPN小鼠的伤害性行为和PD-L1的镇痛作用是性二态的,在即将进行的PIPN机理研究中,强调将性别作为关键生物学因素的重要性,并为潜在的性别特异性治疗方法提供见解。
    OBJECTIVE: Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions.
    METHODS: Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 μL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1β were measured via RT-PCR.
    RESULTS: TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression.
    CONCLUSIONS: PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.
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  • 文章类型: Journal Article
    提出了一种由透明质酸接枝多巴胺(HADA)和设计肽HGF-(RADA)4-DGDRGDS(HRR)组成的生物启发水凝胶,以增强脊髓损伤(SCI)后的组织整合。HADA/HRR水凝胶以平行模式操纵PDGFRβ细胞的浸润,将致密的疤痕转化为引导轴突再生长的对齐的纤维基质。NT3和姜黄素的进一步掺入促进轴突再生和中间神经元在病变边界的存活,它用作中继,以特定于目标的方式建立异构轴突连接。电机的显著改进,感官,膀胱功能导致大鼠脊髓完全横断。HADA/HRR+NT3/Cur水凝胶促进V2a神经元在腹侧脊髓的积累,促进运动功能的恢复。同时,通过神经元中继以特定于靶标的方式记录了犬科动物半球病变上异质神经连接的建立,显著改善电机功能。因此,生物材料可以激发SCI修复的有益生物活性。
    A bioinspired hydrogel composed of hyaluronic acid-graft-dopamine (HADA) and a designer peptide HGF-(RADA)4-DGDRGDS (HRR) was presented to enhance tissue integration following spinal cord injury (SCI). The HADA/HRR hydrogel manipulated the infiltration of PDGFRβ+ cells in a parallel pattern, transforming dense scars into an aligned fibrous substrate that guided axonal regrowth. Further incorporation of NT3 and curcumin promoted axonal regrowth and survival of interneurons at lesion borders, which served as relays for establishing heterogeneous axon connections in a target-specific manner. Notable improvements in motor, sensory, and bladder functions resulted in rats with complete spinal cord transection. The HADA/HRR + NT3/Cur hydrogel promoted V2a neuron accumulation in ventral spinal cord, facilitating the recovery of locomotor function. Meanwhile, the establishment of heterogeneous neural connections across the hemisected lesion of canines was documented in a target-specific manner via neuronal relays, significantly improving motor functions. Therefore, biomaterials can inspire beneficial biological activities for SCI repair.
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  • 文章类型: Journal Article
    Objective: To summarize the clinical manifestations, diagnosis, treatment and prognosis of acute flaccid myelitis (AFM) in children. Methods: Clinical characteristics of 4 AFM cases from Department of Neurology, Children\'s Hospital Affiliated to Capital Institute of Pediatrics, from September 2018 to November 2022, were analyzed retrospectively. Results: The age of 4 children with AFM was 7 years, 4 years and 3 months, 7 years and 1 month, 6 years and 5 months, respectively. There were 2 boys and 2 girls. Prodromal infection status showed 3 children of respiratory tract infection and 1 child of digestive tract infection. The main manifestation was asymmetrical limb weakness after infection, and the affected limb range was from monoplegia to quadriplegia. Cranial nerve injury was involved in 1 child, no encephalopathy. Magnetic resonance imaging in the spinal cord of all 4 children showed long T1 and T2 signals, mainly involving gray matter. Cerebrospinal fluid cell-protein separation was observed in 2 children. Pathogen detected in 1 child pharyngeal swab was enterovirus D68. Antibody IgM to adenovirus was positive in the blood of 1 child. Antibody IgG against Echo and Coxsackie B virus were positive in the blood of another child. After glucocorticoid, human immunoglobulin or simple symptomatic treatment and at the same time under later rehabilitation training, muscle strength recovered to different degrees, but there were disabilities left in 3 children. Conclusions: AFM should be considered in children with acute and asymmetrical flaccid paralysis accompanied by abnormal magnetic resonance imaging signal in the central region of spinal cord, especially post-infection. The effective treatment is limited and the prognosis is poor.
    目的: 总结儿童急性弛缓性脊髓炎(AFM)的临床表现、诊治经验和预后。 方法: 回顾性病例总结,对首都儿科研究所附属儿童医院神经内科2018年9月至2022年11月收治的4例临床诊断AFM患儿的病例资料进行临床特点分析。 结果: 4例AFM患儿年龄分别为7岁、4岁3月龄、7岁1月龄、6岁5月龄,女2例、男2例。前驱呼吸道感染3例、消化道感染1例。以感染后出现不对称肢体无力为主要表现,受影响肢体范围从单一肢体到四肢。所有患儿均无脑病表现,1例患儿出现周围性面瘫。4例患儿脊髓磁共振成像均提示长节段长T1长T2信号,以灰质受累为主。2例患儿出现脑脊液细胞-蛋白分离现象。1例咽拭子病原体检出肠道病毒D68;1例患儿血液中腺病毒抗体IgM阳性;1例患儿血液中埃可病毒、柯萨奇B组病毒抗体IgG阳性。4例患儿经过糖皮质激素、人免疫球蛋白或单纯对症治疗,同时在后期康复训练下,肌力不同程度恢复,3例遗留有残疾。 结论: 以感染后、急性、不对称肢体无力起病伴有磁共振成像脊髓中央区域异常信号的患儿需考虑AFM,目前有效治疗手段有限且预后不良。.
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  • 文章类型: Journal Article
    目的:原发性脊髓胶质母细胞瘤(PSCGBM)是一种罕见的恶性肿瘤,预后不良。迄今为止,没有建立这种罕见疾病的预后列线图.因此,我们的目的是建立一个列线图来预测PSCGBM的总生存期(OS)。
    方法:回顾性收集苏州大学附属第二医院神经外科和监测流行病学和最终结果数据库中PSCGBM患者的临床资料。信息包括年龄,性别,种族,肿瘤扩展,切除范围,辅助治疗,婚姻状况,收入,记录诊断年份和从诊断到治疗的月份.单变量和多变量Cox回归分析用于确定PSCGBM的独立预后因素。构建了一个列线图来预测1年,1.5年,和PSCGBM的2年操作系统。
    结果:共纳入132例患者。1年,1.5年,两年OS为45.5%,29.5%,18.9%,分别。四个变量:年龄组,肿瘤扩展,切除范围,和辅助治疗,被确定为独立的预后因素。列线图显示出具有C指数值的稳健判别,用于预测1年的OS,1.5年操作系统,和2年0.71(95%置信区间[CI],0.61-0.70),0.72(95%CI,0.62-0.70),和0.70(95%CI,0.61-0.70),分别。校准曲线在该队列中预测和观察到的生存概率之间显示出高一致性。
    结论:我们首次开发并内部验证了预测PSCGBM生存结局的列线图。列线图有可能帮助临床医生对PSCGBM的生存结果进行个性化预测。
    OBJECTIVE: Primary spinal cord glioblastoma (PSCGBM) is a rare malignancy with a poor prognosis. To date, no prognostic nomogram for this rare disease was established. Hence, we aimed to develop a nomogram to predict overall survival (OS) of PSCGBM.
    METHODS: Clinical data of patients with PSCGBM was retrospectively collected from the neurosurgery department of Soochow University Affiliated Second Hospital and the Surveillance Epidemiology and End Results database. Information including age, sex, race, tumor extension, extent of resection, adjuvant treatment, marital status, income, year of diagnosis and months from diagnosis to treatment were recorded. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for PSCGBM. A nomogram was constructed to predict 1-year, 1.5-year, and 2-year OS of PSCGBM.
    RESULTS: A total of 132 patients were included. The 1-year, 1.5-year, and 2-year OS were 45.5%, 29.5%, and 18.9%, respectively. Four variables: age groups, tumor extension, extent of resection, and adjuvant therapy, were identified as independent prognostic factors. The nomogram showed robust discrimination with a C-index value for the prediction of 1-year OS, 1.5-year OS, and 2-year of 0.71 (95% confidence interval [CI], 0.61-0.70), 0.72 (95% CI, 0.62-0.70), and 0.70 (95% CI, 0.61-0.70), respectively. The calibration curves exhibited high consistencies between the predicted and observed survival probability in this cohort.
    CONCLUSIONS: We have developed and internally validated a nomogram for predicting the survival outcome of PSCGBM for the first time. The nomogram has the potential to assist clinicians in making individualized predictions of survival outcome of PSCGBM.
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  • 文章类型: Case Reports
    Primary central nervous system vasculitis (PACNS) is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous system,involving the brain,spinal cord,and meninges.Tumor-like PNCAS,a rare subtype of PACNS,is often misdiagnosed as intracranial malignancy,and that with spinal cord involvement is even more uncommon.The lack of specific clinical symptoms and imaging manifestations poses a challenge to the diagnosis of PACNS.This report presents a case of tumor-like PACNS with spinal cord involvement based on the pathological evidence,aiming to enrich the knowledge about this condition.
    原发性中枢神经系统血管炎(PACNS)是一种发生在中枢神经系统的主要侵犯脑、脊髓及软脑膜的中小血管的血管炎性疾病。瘤样PNCAS是PACNS的少见亚型,常被误诊为颅内恶性肿瘤,脊髓受累在PACNS中更为罕见。PACNS因临床症状及影像学表现缺乏特异性,早期诊断困难。本文报道1例经病理确诊合并脊髓受累的瘤样PACNS,以提高对该病的认识。.
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  • 文章类型: Journal Article
    背景:特发性急性横贯性脊髓炎(IATM)是一种脊髓局灶性炎症性疾病,可导致运动,感官,和自主神经功能障碍。然而,IATM患者的MRI阴性和MRI阳性的比较分析很少报道.
    目的:本研究的目的是比较IATM患者MRI阴性和MRI阳性组,分析预后不良的预测因素,从而探讨MRI阴性与预后的关系。
    方法:选取2018年5月至2022年5月南昌大学第一附属医院收治的132例首次发作的IATM患者。根据是否有脊柱MRI病变分为MRI阳性和MRI阴性组,根据随访时EDSS评分是否≥4,预后良好和预后不良。采用logistic回归模型分析IATM患者预后不良的预测因素。
    结果:在132名患者中,107名符合IATM标准的首次发作患者被纳入研究。我们发现43例(40%)患者的脊髓MRI阴性,而27例(25%)患者被确定为预后不良(随访时EDSS评分≥4).与MRI阴性患者相比,MRI阳性组更有可能出现背部/颈部疼痛,脊髓休克和不良预后,随访时EDSS评分较高。我们还确定了不良结局的三个风险因素:缺乏二线治疗,最低点EDSS评分高,MRI结果阳性。
    结论:与MRI阴性组相比,MRI阳性患者更有可能出现背部/颈部疼痛,脊髓休克和不良预后,随访时EDSS评分较高。没有二线治疗,在最低点EDSS得分高,MRI阳性是首次发作IATM患者预后不良的危险因素.MRI阴性患者预后较好,IATM患者的主动二线免疫治疗可能改善临床结局.
    BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported.
    OBJECTIVE: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis.
    METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models.
    RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result.
    CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.
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  • 文章类型: Case Reports
    结节病是一种多器官受累的肉芽肿性疾病,病因仍然未知。神经结节病是神经系统参与结节病。脊髓受累通常是硬膜内,但也可能发生硬脑膜外受累。这里,我们报告了一例30岁的女士,表现为亚急性发作性轻瘫伴膀胱和肠受累,最终被诊断为结节病相关的脊髓病,并具有纵向广泛的横贯性脊髓炎(LETM)表型。
    Sarcoidosis is a granulomatous disorder with multi-organ involvement, and etiology still remains unknown. Neurosarcoidosis is the involvement of the nervous system in sarcoidosis. Spinal cord involvement is usually intra-dural, but extra-dural involvement can also occur. Here, we report a case of 30 years old lady presenting with subacute onset paraparesis with bladder and bowel involvement, which was finally diagnosed as sarcoidosis-associated myelopathy with the longitudinally extensive transverse myelitis (LETM) phenotype.
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  • 文章类型: Editorial
    本期医学磁共振专刊致力于“MR神经成像的先进技术,“由领先的专家撰写的九篇评论文章。评论涵盖了可重复研究实践的进步,沿血管周围空间的扩散张量成像,使用磁化率源分离的髓鞘成像,脊髓定量MRI分析,视觉白质通路的示踪法,基于深度学习的图像增强,动脉自旋标记,影像组学的潜力,和基于MRI的脑氧代谢定量。这些文章提供了有关尖端技术及其在临床和研究环境中的应用的全面更新,强调它们对提高诊断准确性和理解神经系统疾病的影响。
    This special issue of Magnetic Resonance in Medical Sciences is dedicated to \"Advanced Techniques for MR Neuroimaging,\" featuring nine review articles authored by leading experts. The reviews cover advancements in reproducible research practices, diffusion tensor imaging along the perivascular space, myelin imaging using magnetic susceptibility source separation, spinal cord quantitative MRI analysis, tractometry of visual white matter pathways, deep learning-based image enhancement, arterial spin labeling, the potential of radiomics, and MRI-based quantification of brain oxygen metabolism. These articles provide a comprehensive update on cutting-edge technologies and their applications in clinical and research settings, highlighting their impact on improving diagnostic accuracy and understanding of neurological disorders.
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