一种检测细胞中蛋白质和脂质量的新技术可帮助外科医生发现肉眼无法看到的脑肿瘤组织。目前,脑手术牵涉到许多的猜测。因为很难区分脑肿瘤与正常脑组织,神经外科医生常常在手术时依赖像组织颜色和质地等可见的线索。在许多手术中,本来可以被安全去除的肿瘤组织却意外地被留了下来。由Daniel Orringer及其同事研发的新技术依靠拉曼光谱检测法,它能通过检测化学键的振动来对组织中的脂质和蛋白质的丰富程度进行测绘。肿瘤有着相对较高含量的蛋白及相对较低的脂质,而正常脑组织则两者皆含量丰富。Orringer及其同事应用一种特殊的高功率类型的拉曼光谱检测法——叫做受激拉曼散射或SRS,它能让研究人员快速地对小鼠中的脑肿瘤成像。
为了给图像添加色彩,研究人员对拉曼信号进行编码——使脂质呈绿色,蛋白呈蓝色,因此肿瘤看上去大多呈蓝色而正常组织则显示大量的绿色。正如所料,他们看到癌细胞在组织中紧密地挤在一起并观察到束状的轴突——即长的纤维状的神经元——会像高速公路那样帮助癌细胞在大脑的各处穿行。研究人员还在脑手术时将SRS应用于活体小鼠并展示,SRS可在活体脑的区域中给肿瘤成像,而在这些区域中肿瘤组织对肉眼来说看上去是正常的。在肿瘤与正常组织之间的边缘地带,研究人员看到有细胞(推测是肿瘤细胞)向正常脑组织渗透。Orringer及其同事目前正在构建一种基于SRS成像的牙刷大小的手持式探头,神经外科医生在手术时有可能会无需除去组织而对脑组织进行分析。生物谷(Bioon.com)
生物谷推荐的英文摘要
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3005954
Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy
Minbiao Ji1,*, Daniel A. Orringer2,*, Christian W. Freudiger1, Shakti Ramkissoon3,4, Xiaohui Liu5, Darryl Lau2, Alexandra J. Golby5,6, Isaiah Norton5, Marika Hayashi4, Nathalie Y. R. Agar5,6, Geoffrey S. Young6, Cathie Spino7, Sandro Santagata3, Sandra Camelo-Piragua8, Keith L. Ligon3,4,9, Oren Sagher2 and X. Sunney Xie1,†
Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. We describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from nonneoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and hematoxylin and eosin microscopy for detection of glioma infiltration (κ = 0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct.