Mattfeldt T, Eckel S, Fleischer F, Schmidt V
Department of Pathology, University of Ulm, Oberer Eselsberg M23, D-89081 Ulm, Germany.
J Microsc. 2006 Aug;223(Pt 2):107-19. doi: 10.1111/j.1365-2818.2006.01604.x.
Blood capillaries are thread-like structures that may be considered as an example of a spatial fibre process in three dimensions. At light microscopy, the capillary profiles appear as a planar point process on sections. It has recently been shown that the observed pair correlation function g(r) of the centres of the fibre profiles on two-dimensional sections may be used to estimate the reduced pair correlation function of stationary and isotropic fibre processes in three dimensions. In the present study, we explored how this approach may be extended to statistical analysis of reduced g-functions of capillaries from multiple specimens of different groups and with replicated observations. The methods were applied to normal prostatic tissue compared with prostate cancer. Confidence intervals for the mean reduced g-functions of groups were estimated for fixed r-values parametrically using the t-distribution, and by bootstrap methods. Each estimated reduced g-function was furthermore characterized in terms of its first maximum and minimum. The mean length of capillaries per unit tissue volume was significantly higher in prostate cancer tissue than in normal prostate tissue. Significant differences between the mean reduced g-functions of malignant and benign lesions could be demonstrated for two domains of r-values. In general, bootstrap-based confidence intervals were slightly wider than parametrically estimated confidence intervals. Falsely negative lower bounds of the intervals, which sometimes arose using the parametric approach, could be avoided by the bootstrap method. Testing of group mean values for significant differences by the bootstrap method yielded more conservative results than multiple t-tests. The functional value of the first maximum of the reduced g-function and a global statistical parameter of short-range ordering was significantly reduced in the carcinoma group. Prostate cancer tissue is more densely supplied with capillaries than normal prostate tissue and the three-dimensional arrangement of the vessels differs with respect to interaction at various distance ranges. In the local approach used here, bootstrap methods can be used as a robust statistical tool for the computation of confidence intervals and group comparisons of mean reduced g-functions at specific ranges of interaction.
毛细血管是丝状结构,可被视为三维空间纤维过程的一个例子。在光学显微镜下,毛细血管轮廓在切片上表现为平面点过程。最近的研究表明,二维切片上纤维轮廓中心的观测对关联函数g(r)可用于估计三维静止和各向同性纤维过程的约化对关联函数。在本研究中,我们探讨了如何将这种方法扩展到对来自不同组多个样本且有重复观测的毛细血管约化g函数的统计分析。这些方法应用于正常前列腺组织与前列腺癌的比较。对于固定的r值,使用t分布并通过自助法参数估计组的平均约化g函数的置信区间。此外,每个估计的约化g函数根据其第一个最大值和最小值进行表征。前列腺癌组织中每单位组织体积的毛细血管平均长度显著高于正常前列腺组织。在r值的两个范围内,可以证明恶性和良性病变的平均约化g函数之间存在显著差异。一般来说,基于自助法的置信区间比参数估计的置信区间略宽。使用参数方法时有时出现的区间下限假阴性情况可以通过自助法避免。通过自助法检验组均值的显著差异比多次t检验产生更保守的结果。癌组中约化g函数第一个最大值的功能值和短程有序的全局统计参数显著降低。前列腺癌组织的毛细血管供应比正常前列腺组织更密集,并且血管的三维排列在不同距离范围内的相互作用方面有所不同。在这里使用的局部方法中,自助法可以用作一种稳健的统计工具,用于计算置信区间以及在特定相互作用范围内对平均约化g函数进行组间比较。