基于VBM-Dartel方法对阿兹海默症和轻度认知功能障碍患者的脑组织结构分析

目的:利用MRI图像研究轻度认知功能障碍(MCI)、轻度阿尔茨海默病(AD)患者和健康对照组(HC)两两组间灰质和白质体积改变的特点。方法:利用DARTEL算法对14例AD患者(AD组)、21例MCI患者(MCI组)及23例健康对照组(HC组)的MRI图像(数据均来于于ADNI数据库)进行预处理,再对MCI组、AD组和HC组的全脑灰质和白质体积进行基于体素的统计学比较分析。结果:灰质变化:与HC组比较,AD组的双侧海马、海马旁回、杏仁核、丘脑、颞中回、尾状核及右侧岛叶、梭状回、前扣带皮层、舌回、内嗅皮层、左侧豆状壳核和顶下小叶等结构灰质体积萎缩。MCI组右侧海马、海马旁回、杏仁核、楔前叶、额上回、双侧额中回和豆状壳核等结构的灰质体积萎缩。AD组相较于MCI组在右侧海马、丘脑、楔叶的灰质体积萎缩。白质变化:与HC组比较,AD组双侧Extra-Nuclear、Sub-Gyral、胼胝体、前扣带回和右侧海马旁回白质体积萎缩。MCI组双侧海马旁回、右侧丘脑、Extra-Nuclear和左侧梭状回白质体积萎缩。AD组相较于MCI组在双侧Sub-Gyral、右侧前扣带回、左侧中央后回白质体积萎缩。结论:基于体素的MRI形态学测量能够客观揭示MCI和AD早期阶段的脑灰质和白质结构萎缩,对于AD的早期诊断和监测MCI向AD的转变提供了很好的依据和方法。     

Cannabis,Cigarettes, and Their Co-Occurring Use: Disentangling Differences in Gray Matter Volume

Background:

Structural magnetic resonance imaging techniques are powerful tools for examining the effects of drug use on the brain. The nicotine and cannabis literature has demonstrated differences between nicotine cigarette smokers and cannabis users compared to controls in brain structure; however, less is known about the effects of co-occurring cannabis and tobacco use.

Methods:

We used voxel-based morphometry to examine gray matter volume differences between four groups: (1) cannabis-dependent individuals who do not smoke tobacco (Cs); (2) cannabis-dependent individuals who smoke tobacco (CTs); (3) cannabis-naïve, nicotine-dependent individuals who smoke tobacco (Ts); and (4) healthy controls (HCs). We also explored associations between gray matter volume and measures of cannabis and tobacco use.

Results:

A significant group effect was observed in the left putamen, thalamus, right precentral gyrus, and left cerebellum. Compared to HCs, the Cs, CTs, and Ts exhibited larger gray matter volumes in the left putamen. Cs also had larger gray matter volume than HCs in the right precentral gyrus. Cs and CTs exhibited smaller gray matter volume than HCs in the thalamus, and CTs and Ts had smaller left cerebellar gray matter volume than HCs.

Conclusions:

This study extends previous research that independently examined the effects of cannabis or tobacco use on brain structure by including an examination of co-occurring cannabis and tobacco use, and provides evidence that cannabis and tobacco exposure are associated with alterations in brain regions associated with addiction.     

基于小波分析和灰度纹理特征的乳腺X线图像微钙化点区域的提取

目的乳腺癌的早期发现对患者意义重大。为帮助医生进行乳腺癌的早期检查和诊断,本文提出利用小波分析与图像纹理特征提取相结合的方法来提取乳腺X线图像微钙化点区域,在提高检查准确性的同时避免漏检误检。方法首先利用灰度共生矩阵所提取的能量、熵、对比度、相关性以及小波分解后得到的各层高频系数的方差、能量作为图像的特征向量,然后利用支持向量机进行训练建立最优分类模型。最后利用建立的最优分类模型实现乳腺X线图像微钙化点区域的提取并利用检出率和误检率对结果进行评估。结果使用临床数据进行验证,结果表明利用小波分析与图像纹理特征提取相结合的方法能有效提取乳腺图像中的微钙化点区域。结论基于小波分析和灰度纹理特征的乳腺X线图像微钙化点区域的提取方法比单一的图像纹理特征提取或小波分析等方法,提取的效果更好。另外,该方法设计简单,更易于实现乳腺癌的自动化诊断。     

Cognitive Impairment in Multiple Sclerosis: Clinical,Radiologic and Pathologic Insights

Cognitive impairment is a common and debilitating feature of multiple sclerosis (MS) that has only recent gained considerable attention. Clinical neuropsychological studies have made apparent the multifaceted nature of cognitive troubles often encountered in MS and continue to broaden our understanding of its complexity. Radiographic studies have started to decipher the neuroanatomic substrate of MS‐related cognitive impairment and have shed light onto its pathogenesis. Where radiographic studies have been limited by inadequate resolution or non‐specificity, pathological studies have come to the fore. This review aims to provide an overview of the nature of cognitive impairment typically seen in MS and to explore the literature on imaging and pathological studies relevant to its evolution. In particular, the relative contributions of gray (ie, cerebral cortex, hippocampus, thalamus and basal ganglia) and white matter to MS‐related cognitive impairment will be discussed and the importance of interconnectivity between structures highlighted. The pressing need for longitudinal studies combining standardized neuropsychometric, paraclinical and radiographic outcomes obtained during life with post‐mortem tissue analysis after death is presented.     

Anti-tumor effect of the alphavirus-based virus-like particle vector expressing prostate-specific antigen in a HLA–DR transgenic mouse model of prostate cancer

The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F₁ male mice expressing human PSA and HLA-DRB1^*1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV–PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP–PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV–PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8 T cells (19.6 ± 7.4%) produced IFNγ in response to the immunodominant peptide PSA_65–73. In the blood of vaccinated mice, 18.4 ± 4.1% of CD8 T cells were PSA-specific as determined by the staining with H-2D^b/PSA_65–73 dextramers. VLPV–PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8+ T cell infiltration. Tumor growth in VLPV–PSA vaccinated mice was significantly delayed at early time points (p = 0.002, Gehan–Breslow test). Our data suggest that TC-83-based VLPV–PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV–PSA vaccine will undergo further testing for the immunotherapy of prostate cancer.     

beta-Arrestin2, interacting with phosphodiesterase 4, regulates synaptic release probability and presynaptic inhibition by opioids

Most mu-opioid receptor agonists recruit beta-arrestin2, with some exceptions such as morphine. Surprisingly, however, the acute analgesic effect of morphine is enhanced in the absence of beta-arrestin2. To resolve this paradox, we examined the effects of morphine and fentanyl in acute brain slices of the locus coeruleus and the periaqueductal gray from beta-arrestin2 knockout mice. We report that, in these mice, presynaptic inhibition of evoked inhibitory postsynaptic currents was enhanced, whereas postsynaptic G protein-coupled K(+) (Kir3/GIRK) currents were unaffected. The frequency, but not amplitude, of miniature inhibitory postsynaptic currents was increased in beta-arrestin2 knockout mice, indicating a higher release probability compared to WT mice. The increased release probability resulted from increased cAMP levels because of impaired phosphodiesterase 4 function and conferred an enhanced efficacy of morphine to inhibit GABA release. Thus, beta-arrestin2 attenuates presynaptic inhibition by opioids independent of mu-opioid receptor-driven recruitment, which may make beta-arrestin2 a promising target for regulating analgesia.     

激活似然估计法分析运动相关专业人员脑灰质可塑性

目的 采用激活似然估计（ALE）荟萃分析方法观察长期专业技能训练诱发运动相关专业人员大脑灰质结构的可塑性。方法 于CNKI、PubMed、Web of Science数据库及Google scholar检索2005年1月1日-2020年6月12日基于体素形态学分析（VBM）运动相关专业人员大脑灰质变化的文献,以Ginger ALE软件包对检索结果进行Meta分析。结果 共纳入21项研究,包括396名专业运动员（试验组）和538名健康对照者（对照组）。与对照组相比,试验组左侧脑岛、右侧顶下小叶、右侧额中回、右侧前扣带回、左侧楔前叶及右侧颞上回灰质体积增大;右侧小脑前叶、右侧小脑顶、左侧海马旁回、右侧丘脑、右侧小脑后叶、右侧额上回及左侧楔前叶灰质密度增加。结论 运动相关专业人员多个脑区灰质结构可塑性可能与其所受长期专业技能训练相关。     

Cortical thickness as predictor of response to exercise in people with Parkinson's disease

We previously showed that dual‐task cost (DTC) on gait speed in people with Parkinson''s disease (PD) improved after 6 weeks of the Agility Boot Camp with Cognitive Challenge (ABC‐C) exercise program. Since deficits in dual‐task gait speed are associated with freezing of gait and gray matter atrophy, here we performed preplanned secondary analyses to answer two questions: (a) Do people with PD who are freezers present similar improvements compared to nonfreezers in DTC on gait speed with ABC‐C? (b) Can cortical thickness at baseline predict responsiveness to the ABC‐C? The DTC from 39 freezers and 43 nonfreezers who completed 6 weeks of ABC‐C were analyzed. A subset of 51 participants (21 freezers and 30 nonfreezers) with high quality imaging data were used to characterize relationships between baseline cortical thickness and delta (Δ) DTC on gait speed following ABC‐C. Freezers showed larger ΔDTC on gait speed than nonfreezers with ABC‐C program (p < .05). Cortical thickness in visual and fronto‐parietal areas predicted ΔDTC on gait speed in freezers, whereas sensorimotor‐lateral thickness predicted ΔDTC on gait speed in nonfreezers (p < .05). When matched for motor severity, visual cortical thickness was a common predictor of response to exercise in all individuals, presenting the largest effect size. In conclusion, freezers improved gait automaticity even more than nonfreezers from cognitively challenging exercise. DTC on gait speed improvement was associated with larger baseline cortical thickness from different brain areas, depending on freezing status, but visual cortex thickness showed the most robust relationship with exercise‐induced improvements in DTC.