DSouza Alisha V, Elliott Jonathan T, Gunn Jason R, Barth Richard J, Samkoe Kimberley S, Tichauer Kenneth M, Pogue Brian W
Thayer School of Engineering, Dartmouth College, Hanover NH 03755, USA ;
Thayer School of Engineering, Dartmouth College, Hanover NH 03755, USA.
Biomed Opt Express. 2015 Mar 17;6(4):1304-17. doi: 10.1364/BOE.6.001304. eCollection 2015 Apr 1.
Morbidity and complexity involved in lymph node staging via surgical resection and biopsy could ideally be improved using node assay techniques that are non-invasive. While visible blue dyes are often used to locate the sentinel lymph nodes from draining lymphatic vessels near a tumor, they do not provide an in situ metric to evaluate presence of cancer. In this study, the transport kinetics of methylene blue were analyzed to determine the potential for better in situ information about metastatic involvement in the nodes. A rat model with cancer cells in the axillary lymph nodes was used, with methylene blue injection to image the fluorescence kinetics. The lymphatic flow from injection sites to nodes was imaged and the relative kinetics from feeding lymphatic ducts relative to lymph nodes was quantified. Large variability existed in raw fluorescence and transport patterns within each cohort resulting in no systematic difference between average nodal uptake in normal, sham control and cancer-bearing nodes. However, when the signal from the afferent lymph vessel fluorescence was used to normalize the signal of the lymph nodes, the high signal heterogeneity was reduced. Using a model, the lymph flow through the nodes [Formula: see text] was estimated to be 1.49 ± 0.64 ml/g/min in normal nodes, 1.53 ± 0.45 ml/g/min in sham control nodes, and reduced to 0.50 ± 0.24 ml/g/min in cancer-cell injected nodes. This summarizes the significant difference (p = 0.0002) between cancer-free and cancer-bearing nodes in normalized flow. This process of normalized flow imaging could be used as an in situ tool to detect metastatic involvement in nodes.
通过手术切除和活检进行淋巴结分期所涉及的发病率和复杂性，理想情况下可通过使用非侵入性的淋巴结检测技术来改善。虽然可见蓝色染料常用于从肿瘤附近引流淋巴管定位前哨淋巴结，但它们无法提供评估癌症存在的原位指标。在本研究中，分析了亚甲蓝的运输动力学，以确定获取有关淋巴结转移累及情况更好的原位信息的潜力。使用了腋窝淋巴结中有癌细胞的大鼠模型，注射亚甲蓝以成像荧光动力学。对从注射部位到淋巴结的淋巴流动进行成像，并对相对于淋巴结的输入淋巴管的相对动力学进行量化。每个队列中的原始荧光和运输模式存在很大差异，导致正常、假手术对照和荷瘤淋巴结的平均淋巴结摄取之间没有系统差异。然而，当使用来自输入淋巴管荧光的信号对淋巴结信号进行归一化时，高信号异质性降低。使用一个模型，估计正常淋巴结中通过淋巴结的淋巴流量[公式：见正文]为1.49±0.64毫升/克/分钟，假手术对照淋巴结中为1.53±0.45毫升/克/分钟，而在注射癌细胞的淋巴结中降至0.50±0.24毫升/克/分钟。这总结了无癌和荷瘤淋巴结在归一化流量方面的显著差异（p = 0.0002）。这种归一化流量成像过程可作为一种原位工具来检测淋巴结中的转移累及情况。
