Gajjar Ketan, Heppenstall Lara D, Pang Weiyi, Ashton Katherine M, Trevisan Júlio, Patel Imran I, Llabjani Valon, Stringfellow Helen F, Martin-Hirsch Pierre L, Dawson Timothy, Martin Francis L
Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster, LA1 4YQ, UK ; Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane North, Preston, Lancashire, UK.
Anal Methods. 2012 Sep 6;5:89-102. doi: 10.1039/C2AY25544H.
The most common initial treatment received by patients with a brain tumour is surgical removal of the growth. Precise histopathological diagnosis of brain tumours is to some extent subjective. Furthermore, currently available diagnostic imaging techniques to delineate the excision border during cytoreductive surgery lack the required spatial precision to aid surgeons. We set out to determine whether infrared (IR) and/or Raman spectroscopy combined with multivariate analysis could be applied to discriminate between normal brain tissue and different tumour types (meningioma, glioma and brain metastasis) based on the unique spectral "fingerprints" of their biochemical composition. Formalin-fixed paraffin-embedded tissue blocks of normal brain and different brain tumours were de-waxed, mounted on low-E slides and desiccated before being analyzed using attenuated total reflection Fourier-transform IR (ATR-FTIR) and Raman spectroscopy. ATR-FTIR spectroscopy showed a clear segregation between normal and different tumour subtypes. Discrimination of tumour classes was also apparent with Raman spectroscopy. Further analysis of spectral data revealed changes in brain biochemical structure associated with different tumours. Decreased tentatively-assigned lipid-to-protein ratio was associated with increased tumour progression. Alteration in cholesterol esters-to-phenylalanine ratio was evident in grade IV glioma and metastatic tumours. The current study indicates that IR and/or Raman spectroscopy have the potential to provide a novel diagnostic approach in the accurate diagnosis of brain tumours and have potential for application in intra-operative diagnosis.
脑肿瘤患者最常见的初始治疗方法是手术切除肿瘤。脑肿瘤的精确组织病理学诊断在一定程度上具有主观性。此外,目前在减瘤手术中用于勾勒切除边界的诊断成像技术缺乏帮助外科医生所需的空间精度。我们着手确定红外(IR)和/或拉曼光谱结合多变量分析是否可用于根据正常脑组织和不同肿瘤类型(脑膜瘤、胶质瘤和脑转移瘤)独特的光谱“指纹”来区分它们的生化组成。正常脑和不同脑肿瘤的福尔马林固定石蜡包埋组织块进行脱蜡、安装在低辐射玻璃片上并干燥,然后使用衰减全反射傅里叶变换红外光谱(ATR-FTIR)和拉曼光谱进行分析。ATR-FTIR光谱显示正常组织和不同肿瘤亚型之间有明显区分。拉曼光谱对肿瘤类别也有明显区分。对光谱数据的进一步分析揭示了与不同肿瘤相关脑生化结构的变化。初步确定的脂质与蛋白质比率降低与肿瘤进展增加有关。胆固醇酯与苯丙氨酸比率的改变在IV级胶质瘤和转移瘤中很明显。当前研究表明,红外和/或拉曼光谱有潜力为脑肿瘤的准确诊断提供一种新的诊断方法,并有可能应用于术中诊断。