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. 2016 Apr 12;6:24201. doi: 10.1038/srep24201

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Copyright © 2016, Macmillan Publishers Limited

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(a) Global 3D surface rendering of multiphoton images of MDA-MB-231.Br brain metastases (green) and EdU-tagged nuclei (orange) demonstrating proliferative heterogeneity within the same anatomical region (left) from low proliferation (top right) to high proliferation (bottom right). (b) 3D multiphoton images (top) and associated surface generated images (bottom) focusing on EdU-tagged nuclei (orange) in representative less proliferative (left) and more proliferative (right) PNA.Met1 metastases (K8, green). (c) Kernel density estimation (KDE) plot of the proliferative indices of small, medium, and large MDA-MB-231.Br metastases (left) and plot of the relationship between the proliferative index and the log₁₀ of the tumor volume of each MDA-MB-231.Br metastasis (right). Proliferative index = Total EdU voxel volume/Total tumor voxel volume. (d) Kernel density estimation plot of the proliferative indices of small, medium, and large PNA.Met1 metastases (left) and quadratic regression plot of the relationship between the proliferative index and the log₁₀ of the tumor volume of each PNA.Met1 metastasis (right). Proliferative index is defined as panel C. (e) Schematic representation of concentric zone analysis to analyze spatial characteristics of metastatic proliferation. Zone depth = 10 μm. (f) Regression analyses of the proliferative indices among zones of small (top), medium (middle), and large (bottom) PNA.Met1 brain metastases. Red diamond = mean of each group. P value is based on linear regression model. (g) Bar graphs of the proliferative index within each 10 μm zone for each PNA.Met1 brain metastasis.