Significance: Morphological collagen signatures are important for tissue function, particularly in the tumor microenvironment. A single algorithmic framework with quantitative, multiscale morphological collagen feature extraction may further the use of collagen signatures in understanding fundamental tumor progression. Aim: A modification of the 2D wavelet transform modulus maxima (WTMM) anisotropy method was applied to both digitally simulated collagen fibers and second-harmonic-generation imaged collagen fibers of mouse skin to calculate a multiscale anisotropy factor to detect collagen fiber organization. Approach: The modified 2D WTMM anisotropy method was initially validated on synthetic calibration images to establish the robustness and sensitivity of the multiscale fiber organization tool. Upon validation, the algorithm was applied to collagen fiber organization in normal wild-type skin, melanoma stimulated skin, and integrin α10KO skin. Results: Normal wild-type skin collagen fibers have an increased anisotropy factor at all sizes scales. Interestingly, the multiscale anisotropy differences highlight important dissimilarities between collagen fiber organization in normal wild-type skin, melanoma stimulated, and integrin α10KO skin. At small scales (∼2 to 3 μm), the integrin α10KO skin was vastly different than normal skin (p-value ∼ 10 − 8), whereas the melanoma stimulated skin was vastly different than normal at large scales (∼30 to 40 μm, p-value ∼ 10 − 15). Conclusions: This objective computational collagen fiber organization algorithm is sensitive to collagen fiber organization across multiple scales for effective exploration of collagen morphological alterations associated with melanoma and the lack of α10 integrin binding.

中文翻译：

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小鼠皮肤二次谐波胶原成像的多尺度各向异性分析

意义：形态学胶原蛋白特征对组织功能很重要，尤其是在肿瘤微环境中。具有定量、多尺度形态学胶原特征提取的单一算法框架可以进一步使用胶原特征来理解基本的肿瘤进展。目的：将二维小波变换模量最大值 (WTMM) 各向异性方法的改进应用于小鼠皮肤的数字模拟胶原纤维和二次谐波生成成像胶原纤维，以计算多尺度各向异性因子以检测胶原纤维组织。方法：最初在合成校准图像上验证了改进的 2D WTMM 各向异性方法，以确定多尺度光纤组织工具的稳健性和灵敏度。经验证，该算法应用于正常野生型皮肤、黑色素瘤刺激皮肤和整合素 α10KO 皮肤中的胶原纤维组织。结果：正常野生型皮肤胶原纤维在所有尺寸尺度上都有增加的各向异性因子。有趣的是，多尺度各向异性差异突出了正常野生型皮肤、黑色素瘤刺激皮肤和整合素 α10KO 皮肤中胶原纤维组织之间的重要差异。在小尺度（~2 至 3 μm）下，整合素 α10KO 皮肤与正常皮肤有很大不同（p 值~ 10 - 8），而黑色素瘤刺激的皮肤在大尺度（~30 至 40 μm）下与正常皮肤有很大不同, p 值 ∼ 10 − 15)。结论：