1 南开大学现代光学研究所，天津市微尺度光学信息技术科学重点实验室，天津 300350
2 中国科学院自动化研究所，中国科学院分子影像重点实验室，北京 100190
3 河北医科大学第二医院神经外科，河北 石家庄 050000
脑胶质瘤是一种侵袭性的恶性原发性脑肿瘤，术中准确区分胶质瘤和正常脑组织极具挑战性。基于高分辨偏振敏感光学相干层析术（PS-OCT）对正常小鼠脑和胶质瘤模型小鼠脑进行成像，计算了强度、累积相位延迟和累积光轴信息。结果表明，从PS-OCT图像中可以清楚地显示出鼠脑中的纤维结构及其取向；借助PS-OCT图像中丰富的偏振信息，可以准确区分鼠脑胶质瘤区和正常区；基于计算的光轴标准差可以有效区分胶质瘤和正常脑组织。研究结果表明，高分辨PS-OCT在脑组织成像及脑胶质瘤识别方面具有很大的临床应用潜力。
医用光学 偏振敏感光学相干层析术 脑成像 胶质瘤
Author Affiliations
Abstract
1 Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow 119991, Russia
2 Bauman Moscow State Technical University, Moscow 105005, Russia
3 Institute for Regenerative Medicine, Sechenov University, Moscow 119991, Russia
4 Institute of Solid State Physics of the Russian Academy of Sciences, Chernogolovka 142432, Russia
5 Research Institute of Human Morphology, Moscow 117418, Russia
6 School of Precision Instrument and Optoelectronic Engineering, Tianjin University, Tianjin 300000, China
7 College of Materials Science and Engineering, Sichuan University, Chengdu 610000, China
8 Science Medical Center, Saratov State University, Saratov 410012, Russia
9 Institute of Precision Mechanics and Control, FRC "Saratov Scientific Centre of the Russian Academy of Sciences", Saratov 410028, Russia
Terahertz (THz) technology offers novel opportunities in biology and medicine, thanks to the unique features of THz-wave interactions with tissues and cells. Among them, we particularly notice strong sensitivity of THz waves to the tissue water, as a medium for biochemical reactions and a main endogenous marker for THz spectroscopy and imaging. Tissues of the brain have an exceptionally high content of water. This factor, along with the features of the structural organization and biochemistry of neuronal and glial tissues, makes the brain an exciting subject to study in the THz range. In this paper, progress and prospects of THz technology in neurodiagnostics are overviewed, including diagnosis of neurodegenerative disease, myelin deficit, tumors of the central nervous system (with an emphasis on brain gliomas), and traumatic brain injuries. Fundamental and applied challenges in study of the THz-wave – brain tissue interactions and development of the THz biomedical tools and systems for neurodiagnostics are discussed.
THz technology THz spectroscopy and imaging superresolution imaging biophotonics brain neurodiagnosis tumor glioma neurodegenerative diseases brain injury light scattering Opto-Electronic Advances
2023, 6(5): 220071
Author Affiliations
Abstract
1 Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong, University of Science and Technology, Wuhan, Hubei 430074, P. R. China
2 MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P. R. China
Glioma is the most malignant brain cancer. The neurons, macrophages, T cells and other immune cells constitute the glioma immunosuppressive microenvironment. The accurate spatial distribution of these cells in the glioma microenvironment and its relationship with glioma metastasis is unknown. We constructed a mouse glioma cell line stably expressing the large Stokes-shifted yellow fluorescent protein and applied it to the multicolor immunofluorescence imaging. The imaging data revealed that the neurons were sparsely distributed in the glioma core and the number of neurons decreased by 90% compared with normal brain site. The spatial distribution of monocyte-macrophages and microglia is heterogeneous. The monocyte-macrophages and T cells were heavily recruited into the glioma core and metastasis. There was no significant difference in the distribution of microglia among glioma core, margin, and normal brain site. Our results provided new perspectives for targeting immune regulation cells and developing new immunotherapy strategies for glioma.Glioma is the most malignant brain cancer. The neurons, macrophages, T cells and other immune cells constitute the glioma immunosuppressive microenvironment. The accurate spatial distribution of these cells in the glioma microenvironment and its relationship with glioma metastasis is unknown. We constructed a mouse glioma cell line stably expressing the large Stokes-shifted yellow fluorescent protein and applied it to the multicolor immunofluorescence imaging. The imaging data revealed that the neurons were sparsely distributed in the glioma core and the number of neurons decreased by 90% compared with normal brain site. The spatial distribution of monocyte-macrophages and microglia is heterogeneous. The monocyte-macrophages and T cells were heavily recruited into the glioma core and metastasis. There was no significant difference in the distribution of microglia among glioma core, margin, and normal brain site. Our results provided new perspectives for targeting immune regulation cells and developing new immunotherapy strategies for glioma.
Glioma microenvironment spatial distribution heterogeneity multicolor immunofluorescence large Stokes-shifted fluorescent protein Journal of Innovative Optical Health Sciences
2023, 16(1): 2245005
北京联合大学 智慧城市学院 物联网与机器人实验室, 北京 100101
三维脑胶质瘤磁共振成像肿瘤形状各异、边缘模糊, 目前大多数基于2D卷积神经网络的分割方法不能很好的分割三维图像。为了能够准确分割出三维图像中的肿瘤部分, 提出一种融合多尺度特征信息的3D卷积神经网络脑肿瘤图像分割方法。利用并行的3D空洞卷积提取特征信息, 将不同感受野的信息融合。将Dice损失和BCE损失结合, 形成一种新的损失函数并配合恒等映射, 进一步提高分割精度。在BraTs2020数据集上对模型进行验证, 结果表明, 该模型分割的全肿瘤区、核心区和增强区的Dice系数分别为89.1%、83.9%和82.6%。在LGG脑部肿瘤图像数据集上对模型进行验证, 结果表明, Dice系数达到了93.3%。所提出的分割方法不仅能够精确的分割三维脑胶质瘤图像, 而且同样适用于分割二维脑胶质瘤图像。
脑胶质瘤 三维磁共振图像 图像分割 3D卷积神经网络 Brain glioma three-dimensional magnetic resonance image image segmentation 3D convolutional neural network
1 四川大学华西医院头颈肿瘤科, 成都 610041
2 重庆市江津区中心医院神经内科, 重庆 402260
激光拉曼光谱是一种可以作为诊断组织分子结构的物理探针, 具有辅助诊断良恶性肿瘤和判断预后的作用。本研究探索应用激光共聚焦拉曼光谱对脑胶质瘤进行快速诊断与分级, 辅助用于术中及术后胶质瘤诊断与鉴别诊断。本研究使用Renishaw InVia激光共聚焦拉曼光谱仪, 采用514 nm激发光源, 测量新鲜Ⅲ、Ⅳ级人脑胶质瘤组织及正常人脑组织样本共计14例。结果显示: 采用绝对峰位移比较、特征峰位移比值、聚类分析等方法分析激光共聚焦拉曼光谱检测数据, 证实正常脑组织与脑胶质瘤组织在1 664、2 852、2 882和2 930 cm–1处表现出明显的拉曼位移差异; Ⅲ级、Ⅳ级脑胶质瘤组织之间亦在1 235、1 260、1 311、1 360、1 583、1 660、3 160和3 300 cm–1处表现出明显的拉曼绝对位移差异, 并在I1 660/I1 583、I1 311/I1 360、I1 235/I1 360等处表现出显著的、具有诊断意义的相对位移差异。综上, 利用激光共聚焦拉曼光谱能区分脑胶质瘤与正常脑组织, 鉴别诊断Ⅲ、Ⅳ级脑胶质瘤分级准确率可达86%。因此, 激光共聚焦拉曼光谱是一种可行、准确的对脑胶质瘤进行诊断与分级的辅助手段。
激光共聚焦拉曼光谱 Ⅲ/Ⅳ级脑胶质瘤 拉曼位移差异 诊断 分级 Raman spectroscopy grade Ⅲ & Ⅳ glioma Raman shift difference diagnosis grade
上海理工大学 光电信息与计算机工程学院，上海 200093
太赫兹波因其指纹谱识别和无损探测等特性可被应用于物质的快速定性与定量识别。现阶段太赫兹技术方法对物质含量检测的下限在毫克量级，然而实际生物医学样本中待测物的浓度通常在微克量级甚至以下，现有方法限制了其检测灵敏度和可行性。研究中以脑胶质瘤里的特异性物质肌醇(MI)和γ-氨基丁酸(GABA)为例，基于电容电感效应，设计了一款增强太赫兹检测灵敏度的超材料芯片。然后通过测试MI和GABA在不同浓度下的太赫兹光谱，证明其各自随着浓度的变化，芯片谐振峰频移呈现不同的规律，从而进行有效的定性识别，且对于MI和GABA的已知样品，可以根据频移规律实现定量分析。根据实验数据计算可得，所设计的芯片对这两种样品含量检测下限分别为3.457 µg和2.552 µg，与传统压片法的检测极限相比提高了三个数量级。这些结果对后期生物医学中定性和定量检测疾病的微量特异性物质具有重要参考价值。
超材料传感芯片 太赫兹 高灵敏检测 脑胶质瘤 metamaterial sensor chip terahertz high sensitivity detection brain glioma disease 红外与激光工程
2021, 50(8): 20210279
为了深入研究人脑胶质瘤治疗时耐药的发生机制, 并寻求潜在的治疗手段, 以人脑胶质瘤细胞U251为研究对象, 研究肿瘤坏死因子α诱导蛋白1(TNFAIP1)对其迁移和侵袭的影响。半定量PCR和蛋白质免疫印迹(Western blot)试验发现, 替莫唑胺(TMZ)会上调U251细胞内TNFAIP1的表达。在U251细胞中过表达TNFAIP1后, 发现上调TNFAIP1的表达能促进TMZ对U251细胞迁移及侵袭的抑制作用, 并且这一作用是通过抑制上皮-间充质转化(EMT)信号通路来实现的。这一发现有助于为人脑胶质瘤的临床治疗提供新的理论依据, 为其治疗方法提供新的策略。
人脑胶质瘤 细胞侵袭 human glioma TNFAIP1 TNFAIP1 TMZ TMZ cell invasion EMT EMT
中国科学院长春光学精密机械与物理研究所, 吉林 长春 130033
高光谱成像(HSI)是一种新兴的快速、 安全的现代医学检测技术。 将自行研制的高光谱成像仪与显微镜相结合, 对人源脑胶质瘤小鼠和H&E染色病理切片进行成像光谱研究。 通过对脑胶质瘤与正常脑组织的高光谱数据进行分析和处理, 获取二者之间的光谱差异以实现对脑胶质瘤与正常脑组织的区分。 实验结果表明, 无论是病理切片还是在体脑组织数据, 脑胶质瘤与正常脑组织反射光谱中特定光谱范围内的反射率均存在一定差异, 可据此对二者进行区分, 为今后临床实验与脑胶质瘤术中辅助诊断提供依据和参考。
高光谱成像 反射光谱 脑胶质瘤 Hyperspectral imaging Reflectance spectrum Glioma 光谱学与光谱分析
2020, 40(12): 3784
1 华东理工大学 药学院, 上海新药设计重点实验室, 上海 200237
2 华东理工大学 材料科学与工程学院, 上海 200237
为了开发一种新型的非病毒无机基因载体, 采用3-氨丙基三乙氧基硅烷(APTMS)和聚乙烯亚胺(PEI)对嵌入型双介孔氧化硅球(EDMSNs)进行改性, 分别得到EDMSNs-NH2和EDMSNs-PEI, 并比较了两种载体结合和保护pCMV-EGFP-N1质粒(pDNA)的能力及细胞转染性能。利用透射电镜、动态光散射及氮气吸附-脱附实验对材料的颗粒形态, 动力学粒径, Zeta电位及孔结构参数进行表征。结果显示, EDMSNs-NH2和EDMSNs-PEI均表现出明显的双介孔结构, 形貌为规整的球形且平均动力学粒径分别为343.2和338.9 nm, 表面电位分别为+18和+43 mV。琼脂糖凝胶电泳、CCK-8法及荧光显微镜结果表明, EDMSNs-PEI对pDNA的担载量为8%, 远高于EDMSNs- NH2(1%)。与PEI和lipofectamine2000相比, EDMSNs-PEI载体展示出更低的细胞毒性。EDMSNs-PEI/pDNA质量比为33 : 1时, EDMSNs-PEI/pDNA对293T细胞的转染效率在72 h达到最大值。因此, 与EDMSNs-NH2相比, EDMSNs-PEI具有更高的正电位及pDNA担载量, 可作为一类有前景的非病毒无机类基因载体用于重大疾病如恶性胶质瘤的治疗。
双介孔氧化硅球 聚乙烯亚胺 基因治疗 恶性胶质瘤 embedded dual-mesoporous silica spheres polyethyleneimine gene therapy malignant glioma
本文使用茴香霉素激活神经胶质瘤U251细胞内c-jun 氨基末端激酶(JNK)活性, 实现激活后的JNK对神经胶质瘤抑瘤效果的探究, 并找到受JNK调节的关键转录因子。试验首先利用在线分析网站预测出受JNK调节的相关肿瘤模型, 通过使用茴香霉素(JNK激动剂)实现对细胞内磷酸化JNK(P-JNK)水平的有效调节, 并通过蛋白质印迹法(Western blot)探究其发挥作用的最适条件; 然后通过Cell Counting Kit-8(CCK-8)检测、细胞计数、细胞划痕和流式细胞检测等试验, 探究激活后的JNK对U251细胞的增殖、迁移能力以及细胞周期的影响; 最后通过转录组测序(RNA-seq)技术分析找到受JNK调节的关键转录因子。试验结果表明: 生物信息数据分析JNK与神经胶质瘤的发生和发展存在很强的相关性; 1.0μg/mL茴香霉素作用于神经胶质瘤U251细胞1.0?h后, 可有效激活细胞内源性JNK活性, 抑制细胞的增殖和迁移, 并导致细胞周期阻滞; RNA-seq分析揭示了JNK可能通过调节P53活性实现抑制神经胶质瘤的生长。本文研究发现, 激活JNK后能够对神经胶质瘤产生抑瘤效果, 为JNK可作为神经胶质瘤的治疗靶点提供了依据, 通过RNA-seq分析找到的转录因子P53为进一步探究JNK影响神经胶质瘤发生发展的机制提供了方向。
神经胶质瘤细胞U251 抑瘤 转录组测序 茴香霉素 JNK JNK glioma cell U251 antitumor effect RNA-seq anisomycin
