PURPOSE Colonoscopy accompanied with biopsy works as the routine endoscopic strategy for the diagnosis of colorectal cancer (CRC) in clinic; however, the colonoscopy is limited to the tissue surface. During the last decades, enabling technologies are emerging to complement with the colonoscopy for better administration of CRC. The conventional low-frequency (<12 MHz) endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) has been widely used to assess the lesion penetration. With the high-frequency ultrasound transducer (>20 MHz), EUS allows more precise visualization of the colorectal abnormalities. In order to achieve the accurate detection or in situ characterization of the colorectal lesions, the EUS diagnosis needs more patho-physiological related information in the micro-structural or molecular level. Quantitative ultrasound (QUS) technique, which could extract the micro-structural information from the ultrasound radio-frequency (RF) signal, is promising for the non-invasive tissue characterization. To date, the knowledge of the high-frequency endoscopic QUS for the CRC characterization has not been fully determined. METHODS In this work, to our best knowledge, it is the first application of the QUS technique based on a customized high-frequency EUS system (30.5 MHz center frequency) to characterize the colorectal malignancies in a VX2 rabbit CRC model. To eliminate the response from the ultrasound electronic system and transducer, the ultrasound signals from colon tissue were calibrated. And, the resulting quasi-liner ultrasound spectra were fit by the linear regression test. As a result, three spectral parameters, including the slope (k), intercept (I) and Midband Fit (M), were obtained from the best-fit line. The three spectral parameters were compared between the malignant tissue regions and adjacent normal tissue regions of the colon tissue specimen ex vivo. The independent t-test was conducted between the three parameters from the normal and malignant group. The statistical method of Fisher Linear Discriminant (FLD) was used to explore the linear combinations of the three parameters, so as to provide more tissue micro-structural features than the single parameter alone. The three FLD values were derived from three different combinations among k, I and M. The threshold was selected from the statistical analysis to optimize the differentiation criteria between the malignant and the normal tissues. The color-coded images were used to display the local FLD values and combined with the EUS B-mode image. RESULTS AND CONCLUSIONS The mean Midband Fit (M) and intercept (I) showed significant differences between the malignant and normal tissue regions. The statistical analysis showed that there were significant differences in all the mean FLD values of the spectral parameter combinations (kI, kM and IM) (t test, P < 0.05). And, the combined image result from the B-mode image and color-coded image could visually correlate with the histology result. In conclusion, the high-frequency endoscopic QUS technique was potential to be used as a complementary method to distinguish the colorectal malignancies by leveraging its morphological and micro-structural ultrasound information.

中文翻译：

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使用高频内窥镜超声定量表征兔模型中的结肠直肠癌

目的 结肠镜检查联合活检作为临床诊断结直肠癌 (CRC) 的常规内镜检查策略；然而，结肠镜检查仅限于组织表面。在过去的几十年里，使能技术不断涌现，以补充结肠镜检查，以更好地管理 CRC。传统的低频 (<12 MHz) 内窥镜超声 (EUS) 引导细针穿刺 (FNA) 已被广泛用于评估病灶渗透。使用高频超声换能器 (>20 MHz)，EUS 可以更精确地显示结直肠异常。为了实现结直肠病变的准确检测或原位表征，EUS诊断需要更多微观结构或分子水平的病理生理相关信息。定量超声（QUS）技术可以从超声射频（RF）信号中提取微结构信息，有望用于非侵入性组织表征。迄今为止，用于 CRC 表征的高频内窥镜 QUS 的知识尚未完全确定。方法 在这项工作中，据我们所知，这是首次应用基于定制高频 EUS 系统（30.5 MHz 中心频率）的 QUS 技术来表征 VX2 兔 CRC 模型中的结直肠恶性肿瘤。为了消除来自超声电子系统和换能器的响应，校准来自结肠组织的超声信号。并且，得到的准线性超声谱通过线性回归测试拟合。因此，三个光谱参数，包括斜率 (k)，截距 (I) 和中频带拟合 (M) 是从最佳拟合线获得的。在离体结肠组织标本的恶性组织区域和相邻正常组织区域之间比较三个光谱参数。在来自正常组和恶性组的三个参数之间进行独立 t 检验。使用Fisher线性判别法(FLD)的统计方法来探索三个参数的线性组合，从而提供比单独单个参数更多的组织微观结构特征。三个 FLD 值来自 k、I 和 M 之间的三种不同组合。阈值是从统计分析中选择的，以优化恶性组织和正常组织之间的区分标准。彩色编码图像用于显示局部 FLD 值并与 EUS B 模式图像结合。结果与结论平均中频带拟合（M）和截距（I）显示恶性和正常组织区域之间的显着差异。统计分析表明，所有光谱参数组合（kI、kM和IM）的平均FLD值均存在显着差异（t检验，P < 0.05）。并且，来自 B 模式图像和彩色编码图像的组合图像结果可以在视觉上与组织学结果相关联。总之，高频内窥镜QUS技术有可能作为一种补充方法，通过利用其形态学和微结构超声信息来区分结直肠恶性肿瘤。结果与结论平均中频带拟合（M）和截距（I）显示恶性和正常组织区域之间的显着差异。统计分析表明，所有光谱参数组合（kI、kM和IM）的平均FLD值均存在显着差异（t检验，P < 0.05）。并且，来自 B 模式图像和彩色编码图像的组合图像结果可以在视觉上与组织学结果相关联。总之，高频内窥镜QUS技术有可能作为一种补充方法，通过利用其形态学和微结构超声信息来区分结直肠恶性肿瘤。结果与结论平均中频带拟合（M）和截距（I）显示恶性和正常组织区域之间的显着差异。统计分析表明，所有光谱参数组合（kI、kM和IM）的平均FLD值均存在显着差异（t检验，P < 0.05）。并且，来自 B 模式图像和彩色编码图像的组合图像结果可以在视觉上与组织学结果相关联。总之，高频内窥镜QUS技术有可能作为一种补充方法，通过利用其形态学和微结构超声信息来区分结直肠恶性肿瘤。统计分析表明，所有光谱参数组合（kI、kM和IM）的平均FLD值均存在显着差异（t检验，P < 0.05）。并且，来自 B 模式图像和彩色编码图像的组合图像结果可以在视觉上与组织学结果相关联。总之，高频内窥镜QUS技术有可能作为一种补充方法，通过利用其形态学和微结构超声信息来区分结直肠恶性肿瘤。统计分析表明，所有光谱参数组合（kI、kM和IM）的平均FLD值均存在显着差异（t检验，P < 0.05）。并且，来自 B 模式图像和彩色编码图像的组合图像结果可以在视觉上与组织学结果相关联。总之，高频内窥镜QUS技术有可能作为一种补充方法，通过利用其形态学和微结构超声信息来区分结直肠恶性肿瘤。