Bhargava Rohit, Fernandez Daniel C, Hewitt Stephen M, Levin Ira W
Department of Bioengineering and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biochim Biophys Acta. 2006 Jul;1758(7):830-45. doi: 10.1016/j.bbamem.2006.05.007. Epub 2006 May 17.
Vibrational spectroscopy allows a visualization of tissue constituents based on intrinsic chemical composition and provides a potential route to obtaining diagnostic markers of diseases. Characterizations utilizing infrared vibrational spectroscopy, in particular, are conventionally low throughput in data acquisition, generally lacking in spatial resolution with the resulting data requiring intensive numerical computations to extract information. These factors impair the ability of infrared spectroscopic measurements to represent accurately the spatial heterogeneity in tissue, to incorporate robustly the diversity introduced by patient cohorts or preparative artifacts and to validate developed protocols in large population studies. In this manuscript, we demonstrate a combination of Fourier transform infrared (FTIR) spectroscopic imaging, tissue microarrays (TMAs) and fast numerical analysis as a paradigm for the rapid analysis, development and validation of high throughput spectroscopic characterization protocols. We provide an extended description of the data treatment algorithm and a discussion of various factors that may influence decision-making using this approach. Finally, a number of prostate tissue biopsies, arranged in an array modality, are employed to examine the efficacy of this approach in histologic recognition of epithelial cell polarization in patients displaying a variety of normal, malignant and hyperplastic conditions. An index of epithelial cell polarization, derived from a combined spectral and morphological analysis, is determined to be a potentially useful diagnostic marker.
振动光谱法能够基于内在化学成分对组织成分进行可视化，并为获取疾病诊断标志物提供了一条潜在途径。特别是利用红外振动光谱法进行的表征，在数据采集方面传统上通量较低，通常缺乏空间分辨率，所得数据需要大量数值计算来提取信息。这些因素削弱了红外光谱测量准确呈现组织空间异质性、稳健纳入患者队列或制备假象所引入的多样性以及在大规模人群研究中验证所开发方案的能力。在本论文中，我们展示了傅里叶变换红外（FTIR）光谱成像、组织微阵列（TMA）和快速数值分析的结合，作为高通量光谱表征方案快速分析、开发和验证的范例。我们对数据处理算法进行了详细描述，并讨论了可能影响使用此方法进行决策的各种因素。最后，采用一些以阵列形式排列的前列腺组织活检样本，来检验该方法在组织学识别显示各种正常、恶性和增生性状况患者上皮细胞极化方面的有效性。通过综合光谱和形态分析得出的上皮细胞极化指数被确定为一个潜在有用的诊断标志物。
