光声物理化学谱检测前列腺癌的机理研究及方法探索

The incident and death rate of prostate cancer (PCa) has an increasing trend in China. The cases are mostly initial diagnosed at medium-late stages. Due to the in sufficient diagnostic accuracy and disease assessment, a realtime, precise and comprehensive diagnostic tool for PCa is needed. Photoacosutic imaging is a realtime, non-radiative and non ionizing biomedical imaging technology.Photoacosutic signals acuired at multiple optical wavelengths include the molecular content and architecture information in the assessed tissue. Photoacoustic physio-chemical analysis is capable of quantifying the contents of tach individual molecular components and the associated microscopic architecture. In the preliminary study of this project, we have successfully identified PCa and quantified its aggressiveness (i.e. Gleason scores). Therefore, the hypothesis of this study is that photoacoustic physio-chemical analysis can quantify the Gleason scores and distribution of cancerous tissues in prostates in vivo, and guide the needle biopsies. The specific aims of this study include: ① Further investigated the mechanism of photoacoustic physio-chemical analysis in PCa diagnosis, establish the mapping between the photoacoustic physio-chemical analysis parameters to the Gleason scores; ② fabricate a miniaturized needle photoacoustic probe based on its prototype and examine the performance of the miniaturized needle photoacoustic probe with phantoms; ③ preliminarily establish the needle photoacoustic probe based diagnostic approach. This research will establish the theoretical foundation of the PCa diagnosis using photoacoustics, and provide a novel concept for the early diagnosis and assessment of PCa.

我国前列腺癌发病率和死亡率呈逐年上升趋势，初诊多为中晚期。现有影像学检查仍不能满足早期诊断的要求，急需一种更准确、全面的检查方法。光声成像是一种基于光声效应的实时、无放射、无电离的生物医学成像方法。多波长的光声信号中包含了组织分子成分及其形成的组织微观结构信息，这些信息可以被光声物理化学谱分析方法量化。前期研究中，我们用此方法成功检测出前列腺癌组织，并与Gleason评分对应，评估其恶性程度。据此，我们推测光声物理化学谱可在体辨别前列腺癌，并量化分析肿瘤的恶性程度及分布，从而更有利诊断和病情评估。我们拟：①进一步探讨光声物理化学谱检测前列腺癌的机制，建立与Gleason评分映射的数学模型；②在自主研发的原型光声探针基础上，建立微型化探针前列腺癌光声检测系统；③初步建立本系统对前列腺癌的检测方法。本课题为前列腺癌光声检测的临床转化奠定了理论基础, 并为本病的早期诊断及病情评估提供了新的思路。

我国前列腺癌发病率和死亡率呈逐年上升趋势，现有影像学检查仍不能满足早期诊断的要求，急需一种更准确、便捷的检查方法。多波长的光声信号中包含了组织分子成分及相应的组织微观结构信息，这些信息可以通过光声物理化学谱量化分析。. 本项目对光声物理化学谱分析法检测前列腺癌的机理进行研究，并对其检测方法进行初步探索。项目首先搭建光声实验平台，用光声物理化学谱分析法处理Gleason评分系统的光声模拟信号，并检测前列腺癌组织切片，捕获前列腺癌的光声分子指纹，总结方法。其次制作微型化光声探针，测试性能参数，适应前列腺检测的需要。最后利用前述平台，在光声探针辅助下检测离体及在体前列腺整体标本，观察光声物理化学谱分析法在实际应用中的价值。. 实验发现：①以MATLAB软件对Gleason评分系统进行信号模拟，检测发现光声谱的斜率大小与Gleason评分对应；以光声物理化学谱分析法捕获前列腺癌光声分子指纹，发现Gleason评分与其光声谱斜率呈线性相关，联合使用中频强度和斜率诊断准确率为79%。所建立的检测方法可鉴别前列腺癌组织并能与Gleason评分关联。②在探针发射波长266nm的光源下，前列腺癌细胞浓度与其总功率谱幅值的对数值呈线性相关；并可检测到犬前列腺边缘纳米颗粒的光声信号。表明制备的光声探针在检测范围及精度等参数上符合实验要求。③实验在光声探针辅助下对人前列腺整体标本进行检测，以支持向量机模型计算ROC决策值，用700nm、1220nm、1370nm三种波长的斜率综合计算，ROC曲线下面积为0.811；诊断敏感度为65.4%，特异度为84.1%。对TRAMP小鼠行活体检测，亦可与病理结果相符。说明探针辅助具有更大的检测范围，能有效评估具有临床意义的侵袭性前列腺癌。. 本项目对光声物理化学谱分析法检测前列腺癌的机理进行了探讨，初步建立了前列腺癌的检测方法，为前列腺癌光声检测的临床转化奠定了理论基础。