Tractostorm: The what,why, and how of tractography dissection reproducibility

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection.” Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC‐ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real‐life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and “virtual dissection” across various laboratories and hospitals. Intra‐rater agreement (Dice score) was approximately 0.77, while inter‐rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.     

Automated classification of depression from structural brain measures across two independent community‐based cohorts

Major depressive disorder (MDD) has been the subject of many neuroimaging case–control classification studies. Although some studies report accuracies ≥80%, most have investigated relatively small samples of clinically‐ascertained, currently symptomatic cases, and did not attempt replication in larger samples. We here first aimed to replicate previously reported classification accuracies in a small, well‐phenotyped community‐based group of current MDD cases with clinical interview‐based diagnoses (from STratifying Resilience and Depression Longitudinally cohort, ‘STRADL’). We performed a set of exploratory predictive classification analyses with measures related to brain morphometry and white matter integrity. We applied three classifier types—SVM, penalised logistic regression or decision tree—either with or without optimisation, and with or without feature selection. We then determined whether similar accuracies could be replicated in a larger independent population‐based sample with self‐reported current depression (UK Biobank cohort). Additional analyses extended to lifetime MDD diagnoses—remitted MDD in STRADL, and lifetime‐experienced MDD in UK Biobank. The highest cross‐validation accuracy (75%) was achieved in the initial current MDD sample with a decision tree classifier and cortical surface area features. The most frequently selected decision tree split variables included surface areas of bilateral caudal anterior cingulate, left lingual gyrus, left superior frontal, right precentral and paracentral regions. High accuracy was not achieved in the larger samples with self‐reported current depression (53.73%), with remitted MDD (57.48%), or with lifetime‐experienced MDD (52.68–60.29%). Our results indicate that high predictive classification accuracies may not immediately translate to larger samples with broader criteria for depression, and may not be robust across different classification approaches.     

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

PD-L1高表达晚期非小细胞肺癌患者单纯免疫治疗与免疫联合化疗疗效比较

背景与目的以免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）为代表的免疫治疗越来越广泛地应用于肺癌治疗。然而，对于程序性死亡受体配体1（programmed cell death-ligand 1, PD-L1）高表达，即肿瘤比例评分（tumor proportion score, TPS）≥50%的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者，采用单纯免疫治疗还是免疫联合化疗在临床上仍存争议。本研究旨在评估PD-L1高表达的晚期NSCLC患者接受单纯免疫治疗与免疫联合化疗的疗效。方法本研究回顾性分析了49例PD-L1高表达晚期NSCLC患者的临床资料。PD-L1表达采用22C3抗体行免疫组化染色，按TPS判读PD-L1表达水平。比较不同临床特征分组患者的客观缓解率（objective response rate，ORR）和无进展生存时间（progression free survival, PFS）。结果免疫单药与免疫联合化疗组的ORR分别为47.1%（8/17）和43.8%（14/32），差异无统计学意义（P=0.825）。免疫单药与免疫联合化疗组的中位PFS分别为8.0个月和6.8个月，差异无统计学意义（P=0.502）。并对本组PD-L1高表达患者免疫治疗的预测因素进行了分析，结果显示，一线免疫治疗ORR（12/19, 63.2%）显著优于二线及以上免疫治疗（10/30, 33.3%），差异有统计学意义（P=0.041），二者间PFS无差异。年龄、性别、吸烟史、功能状态评分（performance status, PS）、病理类型、肿瘤大小、肿瘤淋巴结转移（tumor node metastasis, TNM）分期与ORR和PFS不相关。结论PD-L1高表达的晚期NSCLC患者接受免疫单药和免疫联合化疗的疗效相近。PD-L1高表达患者一线免疫治疗的ORR更佳。对此类人群的最佳治疗方案有待于前瞻性临床研究进一步探索。     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

The Prognostic Role of Peritumoral Edema in Patients with Newly Diagnosed Glioblastoma: A Retrospective Analysis

ObjectivePrevious studies on glioblastomas (GBMs) have not reached a consensus on peritumoral edema (PTE)’s influence on survival. This study evaluated the PTE index’s prognostic role in newly diagnosed GBMs using a well-designed method.MethodsSelected patients were reviewed after a rigorous screening process. Their general information was obtained from electronic medical records. The imaging metrics (MTD, TTM, TTE) representing tumor diameter, laterality, and PTE extent were obtained by manual measurement in Syngo FastView software. The PTE index was a ratio of TTE to MTD. Multiple variables were evaluated using analysis of variance and Cox regression model.ResultsOf 143 patients, 62 were included in this study. MGMT promoter methylation and tumor laterality were both independent prognostic factors (p = 0.020, 0.042; HR = 0.272, 2.630). The lateral tumors’ index was higher than that of the medial tumors (57.7% vs. 42.6%, p = 0.027). Low-index tumors were located in relatively medial positions compared with high-index tumors (TTM, 4.9 vs. 12.8, p = 0.032). This finding indicated that the PTE index tended to increase with tumor laterality. Moreover, the patients with low-index tumors had a significant survival disadvantage in the univariate analysis but not in the multivariate analysis (p = 0.023, 0.220). However, further analysis found that the combination of tumor laterality and PTE statistically stratified the survival outcome. The patients with lateral high-index tumors survived significantly longer (p = 0.022, HR = 1.927).ConclusionsIn contrast with the previous studies, this study recommends combining PTE and tumor laterality for survival stratification in newly diagnosed GBMs.     

Outcomes After Aortic Valve Replacement for Asymptomatic Severe Aortic Regurgitation and Normal Ejection Fraction

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Connectivity measures suggest a sub-cortical generator of myoclonus in Angelman syndrome

ObjectiveThe clinical and neurophysiological characteristics of myoclonus in Angelman syndrome (AS) have been evaluated in single case or small cohorts, with contrasting results. We evaluated the features of myoclonus in a wide cohort of AS patients.MethodsWe performed polygraphic EEG-EMG recording in 24 patients with genetically confirmed AS and myoclonus. Neurophysiological investigations included jerk-locked back-averaging (JLBA), cortico-muscular coherence (CMC) and generalised partial directed coherence (GPDC). CMC and GPDC analyses were compared to those obtained from 10 healthy controls (HC).ResultsTwenty-four patients (aged 3–35 years, median 20) were evaluated. Sequences of quasi-continuous rhythmic jerks mostly occurred at alpha frequency or just below (mean 8.4 ± 1.4 Hz), without EEG correlate. JLBA did not show any clear transient preceding the jerks. CMC showed bilateral over-threshold CMC in alpha band that was prominent on the contralateral hemisphere in the patient group as compared to HC group. GPDC showed a significantly higher alpha outflow from both hemispheres toward activated muscles in the patient group, and a significantly higher beta outflow from contralateral hemisphere in the HC group.ConclusionsThese neurophysiological findings suggest a subcortical generator of myoclonus in AS.SignificanceMyoclonus in AS has not a cortical origin as previously hypothesised.     

基于MRI动态图像观察吞咽时器官动度对头颈部肿瘤调强放疗靶区影响

目的 利用MRI技术连续采集头颈部肿瘤患者吞咽时图像,观察并测量软腭、舌、喉的运动规律及最大活动度。方法 随机选取2018年7月-10月在中国医学科学院肿瘤医院接受调强放疗的原发头颈部恶性肿瘤20例患者,其中男17例、女3例,中位年龄58.5岁(28~78岁)。20例患者中鼻咽癌7例,口腔癌3例,口咽癌5例,下咽癌3例,鼻腔鼻旁窦2例。根据AJCC第八版分期Ⅰ-Ⅱ期患者2例,Ⅲ期8例,Ⅳ期10例。结果 吞咽时软腭向上移动移动距离为(1.06±0.31) cm且服从正态分布,向后移动距离为(0.83±0.24) cm且近似正态分布。舌体向后移动距离为(0.77±0.22) cm,且服从正态分布。含压舌板行图像采集患者舌上移位移为0,无压舌板患者舌体中位上移距离为1.23 cm (0.59~1.41 cm)。喉向上移动距离为(1.14±0.22) cm且服从正态分布,向前移动的中位距离为0.4 cm (0.27~0.90 cm)。结论 吞咽运动有可能发生于头颈部肿瘤患者放疗过程中,并引起大体肿瘤体积(GTV)及周围正常组织移动;因此在制定放疗计划时应注意GTV至PGTV的个体化外放距离,以保证肿瘤处方剂量。     

PDCA循环在消化道肿瘤伴糖尿病患者营养全程管理中的效果观察

目的 探讨PDCA 循环在消化道肿瘤伴糖尿病患者营养全程管理中的效果观察。方法 运用PDCA循环对80例不同程度营养不良的消化道肿瘤伴糖尿病患者实施营养全程管理,比较干预前后患者的体重、BMI指数、糖化血红蛋白、血红蛋白、总蛋白、白蛋白及球蛋白水平。结果 患者血红蛋白、总蛋白、白蛋白及球蛋白水平均有提高,比较差异均有统计学意义(P＜0.05)。结论 PDCA循环管理在消化道肿瘤伴糖尿病患者营养全程管理中有较大的优势, 值得推广。