Selected correlation of epithelial cell mass measures are shown.

<p>Measurements were performed for all of the tissue, the cortex (Ctx), and the medulla (Med). Regression lines and r values of corresponding measurements show how measurements correlate. The curved dotted lines display the confidence limits for the expected mean value. Additional correlations are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161019#pone.0161019.s007" target="_blank">S6 Fig</a>.</p

Correlations of microanatomic features are shown.

<p>(A) Correlation of outer and inner stripe width in millimeters (Out-Stri-mm and Inn-Stri-mm) with fibrosis measures, including all of the tissue, the cortex (Ctx), and the medulla (Med) using image analysis of trichrome (Tri). (B) Correlation of outer and inner stripe width in millimeters (Out-Stri-mm and Inn-Stri-mm) with measures of % epithelial cell mass [EPCM, Epithel below] by visual assessment. Regression lines and r values of corresponding measurements show how measurements correlate. The curved dotted lines display the confidence limits for the expected mean value. Additional correlations are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161019#pone.0161019.s008" target="_blank">S7 Fig</a>.</p

Correlation of selected fibrosis measures is shown.

<p>Image analysis of trichrome (Tri), trichrome analysis minus PAS analysis (T-P), and visual assessment (Vis) were assessed for all of the tissue, the cortex (Ctx), and the medulla (Med). Regression lines and r values of corresponding measurements show how measurements correlate. The curved dotted lines display the confidence limits for the expected mean value. Additional correlations are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161019#pone.0161019.s003" target="_blank">S2 Fig</a>.</p

Correlation of measures of microvessel density (MVD in in vessels/um²) and mean vessel area (MVA in um²) are shown between the cortex (Ctx), and the medulla (Med).

<p>Regression lines and r values of corresponding measurements show how measurements correlate. The curved dotted lines display the confidence limits for the expected mean value. Additional correlations are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161019#pone.0161019.s009" target="_blank">S8 Fig</a>.</p

Renal Medullary and Cortical Correlates in Fibrosis, Epithelial Mass, Microvascularity, and Microanatomy Using Whole Slide Image Analysis Morphometry - Fig 1

<p>Whole slide image (WSI) quantitation is shown for (A) fibrosis using trichrome, (B) basement membrane mass using Periodic acid–Schiff (PAS), (C) fibrosis using collagen III immunohistochemistry, (D) epithelial mass using the red portion of the trichrome, (E) epithelial mass using cytokeratin immunohistochemistry, and (F) using CD34 immunohistochemistry. In (A)-(F), the WSI without quantitation is seen in the upper panel; and a WSI quantitation markup image is shown in the lower panels in which yellow/orange/red areas are counted using a positive pixel count algorithm for (A)-(E) and the microvessel density is quantitated by a microvessel density algorithm in green in (F). The inset in (B) depicts the quantitation of a tubular basement membrane (green arrow) at higher power.</p

Selected correlation of fibrosis measures using collagen III immunohistochemistry (Col) are shown.

<p>Measurements were performed for all of the tissue, the cortex (Ctx), and the medulla (Med). Regression lines and r values of corresponding measurements show how measurements correlate. The curved dotted lines display the confidence limits for the expected mean value. Additional correlations are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161019#pone.0161019.s006" target="_blank">S5 Fig</a>.</p

Measures are shown with regard to the strength of their correlation between cortex and medulla.

<p>Additional correlations are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161019#pone.0161019.s019" target="_blank">S7 Table</a>.</p

A color map of correlations between measured variables is shown.

<p>Variables that correlate closely are clustered.</p

Summary of measurements obtained is shown for various measures of interstitial fibrosis, tubular atrophy, epithelial cell mass [EPCM, Epithel below], microvessel density (MVD), and microvessel area (MVA).

<p>Stains applied include trichrome (Tri), periodic acid–Schiff (PAS), collagen III (Col) immunohistochemistry (IHC), cytokeratin (CK) IHC for EPCM, and CD34 IHC for the MVD and MVA. Measurements are either performed using morphometric or visual (Vis) methods. For fibrosis morphometry, a method employing trichrome minus the PAS measurement is used (T-P). For EPCM, the “Red” of the trichrome is also used (RedTri). The outer (Out) and inner (Inn) stripe (Stri) widths are also measured. (Std Dev = Standard Deviation).</p

Immunohistochemistry of angiogenesis markers.

<p>The explanted HT-29 tumor xenograft on the left and normal liver tissue on the right were stained for CD31 (A), CD34 (B), and vascular endothelial growth factor (VEGF) (C). For CD31 and CD34, the microvessel endothelium was highlighted in both the tumor and in normal liver sinusoids [arrows]. The liver tumors had staining with the endothelial markers CD31 and CD34 at a lower density than the normal liver hepatic sinusoids. Stroma between tumor cell clusters stained with CD31 and CD34 [arrowheads], suggesting an induction of angiogenesis. VEGF showed background staining in the tumor [arrow] at a higher level than normal liver tissue, suggesting cytoplasmic induction of VEGF expression in an attempt by the tumor to induce angiogenesis. Sinusoids in the normal liver tissue stained with VEGF [arrow]. All images are shown at an original magnification of 200x.</p