In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa.
In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa.
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体内非线性光学显微镜（NLOM）的上皮组织界面（ECTI）揭示了仓鼠口腔粘膜中肿瘤的定量测量。
DOI：
10.1371/journal.pone.0116754
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Vargas G
中科院分区：
文献类型：
--
作者：
Pal R;Yang J;Ortiz D;Qiu S;Resto V;McCammon S;Vargas G
上皮-结缔组织界面（ECTI）在包括口腔鳞状细胞癌（OSCC）在内的上皮瘤变中起着不可或缺的作用。由于增殖的上皮支持正常上皮向癌前和癌前细胞的转化，这种界面发生了显著的改变。我们提出了一种基于非线性光学显微镜的方法来直接评估ECTI，并使用仓鼠口腔癌模型量化发育不良改变。采用多光子自体荧光显微镜（MPAM）和二次谐波显微镜（SHGM）对肿瘤和非肿瘤正常粘膜进行体内成像，获得口腔上皮和固有层的横截面重建。对成像部位进行活检，并进行组织病理学分级和ECTI参数测量。使用MPAM-SHGM和组织学测量正常粘膜中ECTI形状参数，计算其与线性几何形状的偏差（ΔLinearity）。在MPAM-SHGM中很容易看到ECTI，定量形状分析显示异常增生中ECTI变形，而正常粘膜中没有。在MPAM-SHGM中，异常增生患者ΔLinearity（0.41±0.24）明显高于正常患者（0.11±0.04）（p < 0.01），组织学结果也证实了ΔLinearity的相似趋势。在不同程度的发育不良中，ΔLinearity的增加也具有统计学意义。体内ΔLinearity仅通过显微镜测量区分异常增生与正常组织的灵敏度为87.9%，特异性为97.6%，而组织学计算的灵敏度为96.4%，特异性为85.7%。在其他可量化的结构变化中，随着发育不良程度的增加，上皮厚度有统计学意义的进行性增加。MPAM-SHGM为直接表征ECTI提供了新的无创方法，可用于临床前研究，以研究该界面在早期转化中的作用。该方法的进一步发展也可能导致新的诊断方法，以区分非肿瘤组织与癌前病变和瘤变，可能与其他细胞和层为基础的异常指标。
The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ΔLinearity. Increase in ΔLinearity was also statistically significant for different grades of dysplasia. In-vivo ΔLinearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in early transformation. Further development of the method may also lead to new diagnostic approaches to differentiate non-neoplastic tissue from precancers and neoplasia, possibly with other cellular and layer based indicators of abnormality.
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DOI：
10.1007/bf02890380
发表时间：
1983-01-01
期刊：
VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY
影响因子：
--
作者：
BOYSEN, M;REITH, A
通讯作者：
REITH, A
影响因子：
3.3
作者：
Oliver, RJ;MacDonald, DG;Felix, DH
通讯作者：
Felix, DH
DOI：
10.1038/nrclinonc.2013.64
发表时间：
2013-06
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Keith RL;Miller YE
通讯作者：
Miller YE
影响因子：
25
作者：
Dombeck, Daniel A.;Harvey, Christopher D.;Tian, Lin;Looger, Loren L.;Tank, David W.
通讯作者：
Tank, David W.
影响因子：
3.5
作者：
Durr, Nicholas J.;Weisspfennig, Christian T.;Ben-Yakar, Adela
通讯作者：
Ben-Yakar, Adela