Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy

Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy
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DOI:
10.1088/0031-9155/59/20/6141
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发表时间:
2014-10-21
影响因子:
3.5
通讯作者:
Notingher, Ioan
Notingher, Ioan
中科院分区:
工程技术2区
文献类型:
--
作者:
Kong, Kenny;Zaabar, Fazliyana;Notingher, Ioan

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保乳手术(BCS)越来越多地用于治疗早期乳腺癌。BCS的关键挑战之一是确保完全切除肿瘤,同时保留尽可能多的健康组织。在这项研究中,我们已经调查了拉曼显微光谱(RMS)的潜力,自动手术中评估肿瘤切除。首先,建立了基于正常和恶性乳腺组织样本的拉曼光谱的多变量分类模型,并以95.6%的灵敏度和96.2%的特异性(5倍交叉验证)实现了乳腺导管癌(DC)的诊断。基于核酸浓度的增加和胶原蛋白和脂肪浓度的降低,将肿瘤区域与健康组织结构区分开。然后将多变量分类模型应用于来自新患者的新鲜组织的切片,以产生DC的诊断图像。通过光栅扫描RMS获得的诊断图像与常规组织病理学诊断一致,但限于长数据采集时间(通常为10 000光谱mm(-2),相当于类似于5 h mm(-2))。使用基于集成的自发荧光成像和拉曼光谱的选择性采样来将拉曼光谱的数量减少到类似于20个光谱mm(-2),这相当于对于5 × 5 mm(2)组织样本的类似于15分钟的采集时间。这项研究表明,选择性采样拉曼显微镜有可能提供一个快速和客观的方法来检测乳腺癌组织和评估切除边缘。
Breast-conserving surgery (BCS) is increasingly employed for the treatment of early stage breast cancer. One of the key challenges in BCS is to ensure complete removal of the tumour while conserving as much healthy tissue as possible. In this study we have investigated the potential of Raman microspectroscopy (RMS) for automated intra-operative evaluation of tumour excision. First, a multivariate classification model based on Raman spectra of normal and malignant breast tissue samples was built and achieved diagnosis of mammary ductal carcinoma (DC) with 95.6% sensitivity and 96.2% specificity (5-fold cross-validation). The tumour regions were discriminated from the healthy tissue structures based on increased concentration of nucleic acids and reduced concentration of collagen and fat. The multivariate classification model was then applied to sections from fresh tissue of new patients to produce diagnosis images for DC. The diagnosis images obtained by raster scanning RMS were in agreement with the conventional histopathology diagnosis but were limited to long data acquisition times (typically 10 000 spectra mm(-2), which is equivalent to similar to 5 h mm(-2)). Selective-sampling based on integrated auto-fluorescence imaging and Raman spectroscopy was used to reduce the number of Raman spectra to similar to 20 spectra mm(-2), which is equivalent to an acquisition time of similar to 15 min for 5 x 5 mm(2) tissue samples. This study suggests that selective-sampling Raman microscopy has the potential to provide a rapid and objective intra-operative method to detect mammary carcinoma in tissue and assess resection margins.