Detection of Cancer in Lymph Nodes by Spectral Imaging

描述(由申请人提供)：这项提案提供的数据表明，可以用新的光谱和数学方法分析淋巴转移癌细胞的存在。这些方法使用红外光谱成像作为数据采集的主要手段，并使用多元统计算法对光谱数据进行分析以产生诊断。 具体地说，这项建议将为检测腋窝淋巴结中的乳腺癌细胞奠定科学基础，这些细胞在肿块切除术和乳房切除术中被切除，以阶段癌症的扩散。这项拟议研究的目标是开发一种基于手术室的仪器，该仪器将在切除淋巴结后15分钟内做出诊断。诊断将以假彩色图像的形式呈现，突出显示乳腺癌细胞和/或继发性肿瘤的存在。 因此，这项研究的里程碑是a)快速样品制备方法的发展，b)成像仪器的改进，c)检测淋巴结转移癌细胞的可靠数据库和算法的构建，以及d)光学诊断方法的灵敏度和特异性的确定。 提出的检测方法的重要性源于这样一个事实，即许多乳腺癌只有在发生转移后才被检测到。在这种情况下，原发肿瘤已经扩散到邻近的淋巴结，需要切除这些淋巴结以阻止疾病的进一步扩散。转移细胞的扩散决定了进一步的行动，如化疗或放射治疗。因此，病理结果的准确性和即刻可获得性至关重要。目前，这些结果通常需要几个小时甚至几天才能得到。 这项建议中描述的方法是基于PI‘s和其他实验室的观察结果，即癌症组织表现出细微的红外光谱差异，从而可以区分活组织中的正常和异常区域。这些差异可以通过从组织切片的微观区域收集数千个单独的光谱(光谱成像)并使用多变量统计分析方法来放大。以这种方式，以伪彩色地图的形式获得图像，其中指示患病区域。一旦建立了其他癌症的数据库，这项研究中开发的方法和技术将很容易转移到受乳腺癌以外的其他癌症影响的淋巴结的分析中。因此，拟议的研究代表了通过新的光学和算法诊断对现有方法的重大改进。

DESCRIPTION (provided by applicant): This proposal presents data that demonstrate that lymph nodes can be analyzed for the presence of metastatic cancer cells by novel spectroscopic and mathematical methods. These methods use Infrared Spectral Imaging as the primary means for data acquisition, and multivariate statistical algorithms for the analysis of spectral data to produce a diagnosis. Specifically, this proposal will establish the scientific foundation for the detection of breast cancer cells in the axillary lymph nodes, excised during lumpectomies and mastectomies, in order to stage the spread of cancer. The goal of the proposed research is the development of an operating room-based instrument that will produce a diagnosis within 15 minutes after excision of a lymph node. The diagnosis will be presented in the form of a pseudo-color image that highlights the presence of breast cancer cells and/or secondary tumors. Thus, the milestones for this research are a) the development of rapid sample preparation methodology, b) the refinement of the imaging instrumentation, c) the construction of reliable databases and algorithms for the detection of metastatic cancer cells in lymph nodes, and d) the determination of sensitivity and specificity of the optical diagnostic method. The significance of the proposed detection method arises from the fact that many breast cancers are detected only after metastases have occurred. In such cases, the primary tumors have spread into adjacent lymph nodes, which need to be removed to stop the further proliferation of disease. The spread of metastatic cells determines further action, such as chemo- or radiation therapy. Thus, the accuracy and immediate availability of pathological results are of utmost importance. Presently, these results often are not available for hours or even days. The methodology described in this proposal is based on the observation from the PI's and other laboratories that cancerous tissue exhibits subtle infrared spectral differences that permit the distinction of normal and abnormal regions in biopsy tissue. These differences can be amplified by collecting thousands of individual spectra from microscopic regions of the tissue section (spectral imaging), and employing multivariate statistical methods of analysis. In this manner, images are obtained, in the form of pseudo-color maps, in which diseased areas are indicated. The methodology and technology to be developed in this research will readily be transferable to the analysis of lymph nodes affected with cancers other than breast cancer, once databases for other cancers are established. Thus, the proposed research represents a major improvement of present methods via novel optical and algorithmic diagnoses.